Ricardo L Armentano

Abstract: New strategies are urgently needed to identify subjects at increased risk of atherosclerotic cardiovascular disease (ACVD) development or complications. A National Public University Center (CUiiDARTE) was created in Uruguay, based on six main pillars: 1) integration of experts in different disciplines and creation of multidisciplinary teams, 2) incidence in public and professional education programs to give training in the use of new technologies and to shift the focus from ACVD treatment to disease prevention, 3) implementation of free vascular studies in the community (distributed rather than centralized healthcare), 4) innovation and application of e-Health and noninvasive technology and approaches, 5) design and development of a biomedical approach to determine the target population and patient workflow, and 6) improvement in individual risk estimation and differentiation between aging and ACVD-related arterial changes using population-based epidemiological and statistical patient-specific models. This work describes main features of CUiiDARTE project implementation, the scientific and technological steps and innovations done for individual risk stratification, and sub-clinical ACVD diagnosis.

Abstract: Traditional methods used to assess cardiovascular risk (i.e. the Framingham Risk Score) exhibit clear limitations. To aid in patient-specific risk stratification and diagnosis it has been proposed to evaluate non-invasively structural and functional arterial parameters. A National Public University Center (CUiiDARTE) was created in Uruguay with the aim of developing and applying strategies to improve cardiovascular risk stratification and sub-clinical vascular disease detection. To this end a health informatics approach and tool was designed, developed and implemented in CUiiDARTE. Its goals were to: (1) promote screening for subclinical atherosclerosis, (2) develop a centralized database to store information obtained noninvasively from anywhere in our country, (3) develop a bio-mathematical model integrating values for arterial structure and function into traditional cardiovascular risk assessment, (4) generate a detailed and comprehensive report for the specialist comparing patient data with reference data from the healthy population, (5) generate a similar report (using a Structural and Functional Arterial Age Calculator) for the patients assessing the state of their arteries. In this work, we present the main characteristics of the CUiiDARTE Health Informatics development.

Abstract: Purpose. To evaluate in chronically haemodialysed patients (CHPs), if: (1) the vascular access (VA) position (upper arm or forearm) is associated with differential changes in upper limb arterial stiffness; (2) differences in arterial stiffness exist between genders associated with the VA; (3) the vascular substitute (VS) of choice, in biomechanical terms, depends on the previous VA location and CHP gender. Methods. 38 CHPs (18 males; VA in upper arm: 18) were studied. Left and right carotid-brachial pulse wave velocity (PWV(c-b)) was measured. In in vitro studies, PWV was obtained in ePTFE prostheses and in several arterial and venous homografts obtained from donors. The biomechanical mismatch (BM) between CHP native vessel (NV) and VS was calculated. Results/Conclusions. PWV(c-b) in upper limbs with VA was lower than in the intact contralateral limbs (P < 0.05), and differences were higher (P < 0.05) when the VA was performed in the upper arm. Differences between PWV(c-b) in upper limbs with VA (in the upper arm) with respect to intact upper limbs were higher (P < 0.05) in males. Independently of the region in which the VA was performed, the homograft that ensured the minimal BM was the brachial artery. The BM was highly dependent on gender and the location in the upper limb in which the VA was performed.

Abstract: The mechanisms that explain intra-aortic balloon pumping (IABP) effects are not completely understood, and attributing them only to pressure-associated changes in cardiac function would be an oversimplification. Since IABP modifies the aortic and systemic blood-flow pattern, flow-related effects could be expected. To characterize effects of acute heart failure (AHF) on the arterial biomechanics; IABP effects on the arterial biomechanics during AHF, and their potential time-dependence; the association between hemodynamics and biomechanical changes during AHF and IABP. Sheep (n = 6) aortic pressure, flow, and diameter were measured: (1) before (Basal) and (2) 1-3 (HF(1-3)) and 28-30 (HF(28-30)) min after starting halothane to induce AHF; and (3) at specific times (1-3, 14-15 and 28-30 min) during IABP assistance. Calculus: aortic characteristic impedance (Z (c)), beta stiffness (β), incremental (E (INC)) and pressure-strain elastic modulus (E (P)); total arterial compliance (C (G)), total systemic vascular resistance and wave propagation parameters. (1) AHF resulted in an acute increase in aortic and systemic stiffness (HF(28-30) % changes with respect to Basal conditions: β +217%, E (P) +143%, E (INC) +101%, Z (c) +52%, C (G) -13%), associated with the reduction in the aortic blood flow; (2) during AHF IABP resulted in acute beneficial changes aortic and systemic biomechanics (% changes in IABP(1-3) with respect HF(28-30): β -62%, E (P) -68%, E (INC) -66%, Z (c) -38%, C (G) 66%), and in wave propagation parameters, (3) IABP-related changes were time-dependent and associated with changes in aortic blood flow. Aortic and systemic biomechanical and impedance properties are detrimentally modified during AHF, being the changes rapidly reverted during IABP. IABP-related beneficial changes in arterial biomechanics were time-dependent and associated with IABP capability to increase blood flow.

Abstract: Study of humans aging has presented difficulties in separating the aging process from concomitant disease and/or in defining normality and abnormality during its development. In accordance with this, aging associates structural and functional changes evidenced in variations in vascular parameters witch suffer alterations during atherosclerosis and have been proposed as early markers of the disease. The absence of adequate tools to differentiate the expected (normal) vascular changes due to aging from those related with a vascular disease is not a minor issue. For an individual, an early diagnosis of a vascular disease should be as important as the diagnosis of a healthy vascular aging. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The arterial pressure waveform can be explained in terms of a reservoir pressure, related to the arterial system compliance, and an "excess" or wave-related pressure, associated with the traveling waves. The aim of this study was to evaluate, by means of a mathematical approach, age-related changes in measured, reservoir and excess central aortic pressure in order to determine if age-related changes are concentrated in particular decades of life. Central aortic pressure waveform was non-invasively obtained in healthy subjects (age range: 20-69 years old). Age-related profiles in measured, reservoir and excess pressure were calculated.

Abstract: BACKGROUND: There is an urgent need of vascular substitutes (VS) to be used in lower limb revascularization procedures when autologous veins are not available and synthetic prosthesis are contraindicated. Since the mechanical differences with respect to native vessels are determinants of the VS failure, the substitutes should have mechanical properties similar to those of the recipient vessels. The use of cryopreserved arteries (cryografts) could overcome limitations of available VS. These work aims were to characterize (a) native vessels/implanted cryografts mechanical and geometrical coupling, (b) cryografts capability to ensure mismatch levels lesser than those expected for expanded polytetrafluoroethylene (ePTFE), (c) cryografts functional properties considering their histological and ultra-structural characteristics. METHODS: Instantaneous pressure (mechano-transducers) and diameter (B-mode echography) were obtained in implanted femoro-popliteal, ileo-femoro-popliteal and axilo-humeral cryografts (n=8), in femoral arteries from recipients (n=8), recipient-like (n=15) and multiorgan donors-like (n=15) subjects, and in ePTFE segments (n=10). Calculus: (a) Mechanical parameters: elastic modulus, arterial compliance, distensibility and characteristic impedance; (b) Arterial remodeling: diameter, wall thickness, cross-sectional area and wall-to-lumen ratio; (c) Native vessels/VS coupling. Histological and structural analysis were done in explanted femoro-popliteal and axilo-humeral cryografts (n=7). RESULTS: Post-implant the cryografts remodeled. Their stiffness increased and the conduit function diminished. Remodeling resulted in an improvement in native vessels/cryograft coupling, which was always better than native vessels/ePTFE coupling. CONCLUSIONS: Post-implant cryograft remodeling improved native vessels/cryografts coupling. Cryografts would have mechanical and geometrical advantages over ePTFE. Anastomotic cryograft remodeling differed from that expected only due to haemodynamic factors. The structural properties of the remodeled cryografts contribute to explain their functional characteristics.

Abstract: A better understanding of the biomechanical properties of the arterial wall provides important insight into arterial vascular biology under normal (healthy) and pathological conditions. This insight has potential to improve tracking of disease progression and to aid in vascular graft design and implementation. In this study, we use linear and nonlinear viscoelastic models to predict biomechanical properties of the thoracic descending aorta and the carotid artery under ex vivo and in vivo conditions in ovine and human arteries. Models analyzed include a four-parameter (linear) Kelvin viscoelastic model and two five-parameter nonlinear viscoelastic models (an arctangent and a sigmoid model) that relate changes in arterial blood pressure to the vessel cross-sectional area (via estimation of vessel strain). These models were developed using the framework of Quasilinear Viscoelasticity (QLV) theory and were validated using measurements from the thoracic descending aorta and the carotid artery obtained from human and ovine arteries. In vivo measurements were obtained from 10 ovine aortas and 10 human carotid arteries. Ex vivo measurements (from both locations) were made in 11 male Merino sheep. Biomechanical properties were obtained through constrained estimation of model parameters. To further investigate the parameter estimates, we computed standard errors and confidence intervals and we used analysis of variance to compare results within and between groups. Overall, our results indicate that optimal model selection depends on the artery type. Results showed that for the thoracic descending aorta (under both experimental conditions), the best predictions were obtained with the nonlinear sigmoid model, while under healthy physiological pressure loading the carotid arteries nonlinear stiffening with increasing pressure is negligible, and consequently, the linear (Kelvin) viscoelastic model better describes the pressure-area dynamics in this vessel. Results comparing biomechanical properties show that the Kelvin and sigmoid models were able to predict the zero-pressure vessel radius; that under ex vivo conditions vessels are more rigid, and comparatively, that the carotid artery is stiffer than the thoracic descending aorta; and that the viscoelastic gain and relaxation parameters do not differ significantly between vessels or experimental conditions. In conclusion, our study demonstrates that the proposed models can predict pressure-area dynamics and that model parameters can be extracted for further interpretation of biomechanical properties.

Abstract: In this work we present an initiative to develop a national (Uruguayan) program to evaluate vascular age and to detect pre-clinical atherosclerosis using: gold-standard technologies; complimentary and integrative approaches to asses arterial functional and structural indexes; data bases systems to process, analyze and determine normal and reference values and to identify the most sensitive markers of vascular changes for different ages. We evaluated, in a Uruguayan population complementary structural and functional vascular parameters that associate aging-related changes and are considered markers of sub-clinical atherosclerosis. Traditional CV risk factors were assessed. The subjects (n=281) were submitted to non-invasive vascular studies to evaluate: 1) Common carotid artery (CCA) intima-media thickness and diameter waveforms, 2) CCA stiffness, 3) aortic stiffness (pulse wave velocity) and 4) peripheral and central pressure pulse wave derived parameters. Age groups: 21-30, 31-40, 41-50, 51-60, and 61-70 years-old. Age-related profiles were obtained for the different vascular parameters, and their utility to assess vascular changes in young, middle-aged and old subjects was evaluated. The work has the strength of being the first that uses, in Latin-America an integrative approach to characterize vascular aging-related changes.

Abstract: Intra-aortic balloon pump (IABP) benefits could depend on variations in the cardiovascular biomechanical properties associated with blood flow-induced endothelium-dependent changes. However, if IABP results in changes in the peripheral artery biomechanics and if the endothelium plays a role in these potential changes remains unknown. The aim of this study is to characterize acute IABP effects on peripheral artery biomechanics in control and acute heart failure (AHF) states and the role of the endothelium in IABP effects on peripheral artery biomechanics. Pressure and diameter were recorded in sheep (n= 7) iliac arteries (IAs), before and during 1:2 IABP, during four states: (i) control with intact IA; (ii) AHF with intact IA; (iii) control with de-endothelialized (DE) (mechanical rubbing) IA; and (iv) AHF with DE IA. Arterial distensibility, elastic modulus, and conduit function (CF) (1/characteristic impedance) were calculated. The results of this study include: (i) during control conditions, IABP resulted in intact IA dilatation, stiffness reduction, and CF increase; (ii) AHF induction determined a reduction in intact IA diameter and CF, and a stiffness increase. These changes reverted during IABP; (iii) the increase in IA stiffness observed after DE remained unchanged during IABP; (iv) in DE IA, AHF did not result in diameter or stiffness changes; and (v) IABP during AHF did not associate changes in diameter or stiffness in the DE IA. In conclusion, during control and AHF states, IABP results in IA dilatation and stiffness reduction. The integrity of the endothelial layer would be critical for the IABP-associated changes in IA biomechanics.

Abstract: Flow-mediated dilatation (FMD) is the most accepted technique for the evaluation of endothelial function. However, it has been show a great inter-subject variability limiting its clinical use. Carotid-radial pulse wave velocity (PWVcr) was proposed as an alternative tool for the evaluation of endothelial function. At the present, there is no doubt that PWVcr reduces its values in response to reactive hyperemia test (RHT) in healthy subjects. Aims: a) to determine simultaneously the temporal profile of FMD, PWVcr and shear rate in response to RHT and b) to describe and analyze how subjects "FMD responders" or "non-responders" behave regards to PWVcr changes. Methods: 34 healthy young subjects were included. The PWVcr (strain gauge mechanotransducers), brachial diameter (B-Mode ultrasound and blood flow velocity (Doppler ultrasound) were measured before (baseline) the cuff was inflated and after its deflation (5 minutes). 10(th) percentiles FMD and PWVcr changes in the population were used for the definition of the subjects ("responders and non-responders"). Results: Changes in PWVcr, brachial arterial diameter and shear rate were evidenced after the cuff release (p<0.05). There were differences in the PWV and FMD temporal profiles. Within "FMD responders" there were "PWV responders and non-responders". Conclusion: Assessing RHT-related changes in PWVcr in the context of a FMD evaluation, could be useful as a discriminator of intrinsic wall alterations giving additional information of vascular dynamics.

Abstract: Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness. However, the absence of standardized methodologies of study and lack of normal and references values have limited wider implementation of PWV in clinical practice. In this work normal PWV levels were determined in a Uruguayan population and the obtained values were analyzed taking into account data from other populations. The differences between the ´real´ PWV levels and the PWV calculated using different wave detection algorithms and path lengths were assessed, and compared the taking into account the changes in PWV with aging. Results: The Uruguayan population showed a rate of PWV increase comparable to that reported previously in non-hypertensive European subjects, although overall, PWV values were approximately 2 m/s higher in the Uruguayan population. The different approaches used to calculate the PWV showed differences in their availability to follow aging-variations in 'adjusted' (or 'real') PWV.

Abstract: This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes.

Abstract: Simultaneous measurement of pressure and diameter in blood vessels or vascular prosthesis is of great importance in cardiovascular research. Knowledge of diameter changes as response to intravascular pressure is the basis to estimate the biomechanical properties of blood vessel. In this work a new method to quantify arterial diameter based in high resolution ultrasonography is proposed. Measurements on an arterial phantom placed on a cardiovascular simulator were performed. The results were compared to sonomicrometry measurements considered as gold standard technique. The obtained results indicate that the new method ensure an optimal diameter quantification. This method presents two main advantages respect to sonomicrometry: is noninvasive and the vessel wall strain can be measured directly.

Abstract: An increasing number of intermediate risk asymptomatic subjects benefit from measures of atherosclerosis burden like coronary artery calcification studies with non-contrast heart computed tomography (CT). However, additional information can be derived from these studies, looking beyond the coronary arteries and without exposing the patients to further radiation. We report a semi-automatic method that objectively assesses ascending, arch and descending aorta dimension and shape from non-contrast CT datasets to investigate the effect of aging on thoracic aorta geometry. First, the segmentation process identifies the vessel centerline coordinates following a toroidal path for the curvilinear portion and axial planes for descending aorta. Then, reconstructing oblique planes orthogonal to the centerline direction, it iteratively fits circles inside the vessel cross-section. Finally, regional thoracic aorta dimensions (diameter, volume and length) and shape (vessel curvature and tortuosity) are calculated. A population of 200 normotensive men was recruited. Length, mean diameter and volume differed by 1.2 cm, 0.13 cm and 21 cm(3) per decade of life, respectively. Aortic shape uncoiled with aging, reducing its tortuosity and increasing its radius of curvature. The arch was the most affected segment. In conclusion, non-contrast cardiac CT imaging can be successfully employed to assess thoracic aorta 3D morphometry.

Abstract: Gender-related difference in cardiovascular diseases is one of the most investigated and still unsolved issues. Finding an explanation to this topic might have important implications for the understanding of the differences between men and women in diseases and possibly lead to the development of gender-specific strategies for its management. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The pressure waveform can be explained in terms of a reservoir pressure related to arterial compliance and an "excess" or wave-related pressure associated with traveling waves. Gender-differences in the ascending aorta pressure waveform reservoir and excess components are to be characterized. The aim of this study was to evaluate, by means of a mathematical approach, gender-related differences in the central aortic pressure waveform components. Central aortic pressure waveform was non-invasively obtained in 22 healthy subjects (Age: 20 years old; 11 female). Males and females showed differences in the level and time to maximal excess pressure component, but no gender-related differences were found in the reservoir one.

Abstract: In several clinical and experimental circumstances, it is widely necessary to characterize the bio-mechanical changes induced by atherosclerosis to the arterial wall. In this context, the purpose of this paper is twofold. Firstly, to propose a low cost ultrasound setup to improve artery radii determination in elasticity experiments, based on two transducers using a single channel ultrasound hardware. Secondly, to present an in vitro artificial heart system developed in our laboratory, which provides a wide range of hemodynamic parameters in arterial elasticity assessment experiments. It can be used in a liquid, stand alone mode or blowing air to a Jarvik device. This system will be integrated in future works with the proposed ultrasound setup to provide real time elasticity measurements.

Abstract: Atherosclerotic plaque complication is a major cause of vascular accidents. Although a variety of factors have been proposed as key factors in these process, the mechanism that contribute to this problem remain to be characterized. Previously we demonstrated that changes in arterial wall viscous and elastic properties and/or in the filtering function (FF) could be part of the arterial wall alterations basis. If these properties are altered in arteries with atherosclerotic plaques remains to be analyzed. Our aims were 1) to analyze the arterial wall visco-elasticity and FF of carotid and femoral segments with atherosclerotic plaques, 2) to compare them with the mechanical behavior of segments without plaques (from the same artery) and of healthy arteries studied non-invasively. To this end, in each arterial segment, pressure and diameter signals were obtained, in vitro (circulation mock) and in vivo (non-invasive recordings). In atherosclerotic arteries recordings were performed on plaques and near regions without plaques. In each segment, the elasticity, the viscosity, and the wall FF were quantified. Atherosclerotic vessels, and particularly plaque regions, showed a reduced viscosity and FF. At the light of our results, hypothetical links between plaque events and changes in visco-elasticity and FF were discussed.

Abstract: Although a variety of factors have been proposed as key factors of the atherosclerotic plaque vulnerability, the mechanisms that contribute to this problem are not yet fully characterized. In previous works we demonstrated that changes in arterial wall viscosity and elasticity and/or in the filtering function (FF) could be in the basis of arterial wall alterations. If these properties are altered in arterial wall with atherosclerotic plaques remain to be analyzed. Our aims were to analyze, the arterial wall visco-elasticity and FF of human carotid arteries with atherosclerotic plaques. To this end, instantaneous arterial diameter waveforms were obtained non-invasively (B-Mode Echography), in five sites (S1-S5) on the carotid artery. After that, diameter waveform obtained in S1 (first segment of the common carotid artery) was calibrated using pressure values, and used to quantify the pressure-diameter relationship for each segment. From pressure-diameter relationships, viscosity, elasticity and FF were quantified. Central portions of atherosclerotic plaques showed a reduced FF. At least in theoretical terms, the FF reduction could be related with the plaque vulnerability.

Abstract: This study uses linear and nonlinear viscoelastic models to describe the dynamic distention of the aorta induced by time-varying arterial blood pressure. We employ an inverse mathematical modeling approach on a four-parameter (linear) Kelvin viscoelastic model and two five-parameter nonlinear viscoelastic models (arctangent and sigmoid) to infer vascular biomechanical properties under in vivo and ex vivo experimental conditions in ten and eleven male Merino sheep, respectively. We used the Akaike Information Criterion (AIC) as a goodness-of-fit measure. Results show that under both experimental conditions, the nonlinear models generally outperform the linear Kelvin model, as judged by the AIC. Furthermore, the sigmoid nonlinear viscoelastic model consistently achieves the lowest AIC and also matches the zero-stress vessel radii measured ex vivo. Based on these observations, we conclude that the sigmoid nonlinear viscoelastic model best describes the biomechanical properties of ovine large arteries under both experimental conditions considered in this study.

Abstract: This study aimed to characterize the following: (i) in chronically hemodialyzed subjects (CHDSs), with and without diabetic nephropathy (DN), and in healthy subjects (non-CHDSs) different arterial pathways stiffness to determine potential pathology-dependent, etiology- and/or pathway-dependent differences; and (ii) the biomechanical mismatch (BM) between arteries from non-CHDSs or CHDSs (with and without DN) and arterial cryografts, venous cryografts, and synthetic prosthesis to determine arterial pathway, pathology, and/or etiology-related differences in the substitute of election in terms of BM. Carotid-femoral and carotid-brachial pulse wave velocity (PWV) were measured in 30 non-CHDSs and 71 CHDSs (11 with DN). In addition, PWV was measured in arterial (elastic and muscular) and venous cryografts and in expanded polytetrafluorethylene prosthesis. The arterial pathways regional differences and the subjects' arterial pathways-substitutes BM were calculated. Arterial stiffness levels and regional differences were higher in CHDS than in non-CHDS. Among CHDS, those with DN showed higher stiffness in the aorto-femoral pathway and larger regional differences. Cryografts showed always the least BM. Non-CHDS and CHDS differed in the cryograft of election. In CHDS, the BM was related with the cryograft type, arterial pathway, and renal disease etiology. The BM could be minimized, selecting the most adequate cryograft type, taking into account the recipient specific characteristic (i.e., arterial pathway and renal disease etiology).

Abstract: The analysis of carotid-radial pulse wave velocity (PWVcr) changes in response to forearm transient ischemia (TI) has been proposed as an alternative approach to evaluate endothelial function. Consider flow mediated dilatation tests, PWVcr changes are characterized after 5 minutes of TI. It is unknown if lower TI times could be used and if different TI times would result in different PWVcr responses (levels and/or kinetics). Objective: To determine PWVcr changes associated with the reactive hyperemia in response to 1, 3 or 5 minutes of forearm TI. Methods: We measured left PWVcr change using mechano-transducers in healthy volunteers (22 ± 2 years old) before (basal) and after 1 (n=14), 3 (n=14) and 5 (n=15) minutes of TI (forearm cuff inflation), respectively. The change of level and rate in PWVcr were recorded at 15, 30, 45 and 60 seconds after cuff release. Right brachial pressure was measured. Results: There were no changes in heart rate or blood pressure during the studies. Regardless of the occlusion length, TI resulted in PWVcr reduction (p < 0.05). The groups showed similar maximum PWVcr reduction. However, there were differences in the immediate PWVcr changes (-4.9 ± 0.2%; -6.8 ± 0.3% and -8.3 ± 0.5% for 1, 3 and 5 minutes of TI, respectively) (p < 0.05). Then, the immediate rate of PWVcr change differed (p < 0.05) among the different ischemia times considered. Thereafter, the differences diminished and a minute after TI the groups showed similar levels and mean rate of PWVcr reduction. Conclusion: Similar maximum PWVcr responses can be obtained after 1, 3, or 5 minutes of TI. Different TI times resulted in dissimilar immediate, but not later, PWVcr changes.

Abstract: The ambulatory arterial stiffness index (AASI) is claimed to be a new estimator for arterial rigidity. It was recently defined as one minus the slope of the linear regression of systolic to diastolic ambulatory pressure during 24 h. Although several reports testify its clinical relevance, the explanation of how this new index is conceptually associated with arterial stiffness remains controversial. In this work we hypothesize that nonlinear arterial elasticity is behind AASI physiological principles. To that end, random number generators were used to emulate arterial cross-sectional area (CSA) during 24 h. Pressure values were calculated using linear and nonlinear elasticity models for rigid and compliant arteries. The AASI was calculated from simulated pressures and also analytically predicted for each model. Additionally, invasive aortic pressure and CSA were continuously measured in a conscious sheep during 24 h to test the nonlinear model. We found that analytical solutions agreed with simulation outcomes; for the nonlinear model, the AASI was higher in rigid arteries with respect to compliant arteries (0.51 versus 0.38) and the linear model systematically predicted AASI = 0. For in vivo pressure measurements, AASI was 0.31. Using the measured pulsatile CSA and an estimation of the elastic constant for the nonlinear model, the AASI was accurately predicted with errors below 5%. We conclude that the AASI is higher in stiffer arteries due to the nonlinear behavior of the arterial wall. With a nonlinear arterial function, the slope of the linear regression of diastolic to systolic pressures during 24 h depends on the product of an elastic constant by the pulsatile CSA. As the elastic constant dominates the product, the reported associations between the AASI and arterial stiffness indices now have a consistent explanation.

Abstract: Assessing the individual geometry of the coronary arteries in a patient can help to explain diffuse artery disease. Some allometric functions, relating arterial length and volume, were verified in porcine arteries and human autopsies but not in vivo. In this work we use skeletonization methods on MSCT images to render the whole coronary tree in healthy and cardiovascular patients. Twenty patients with and without coronary artery disease were recruited. The coronary was segmented with minimum user intervention. Vessels were separated and measured. A 3D coronary map was individually calculated. The allometric length-volume function L=k(v)V(β) was evaluated in each patient and plotted in a Log-Log scale. The coefficient k(v) ranged 1.00 ± 0.35. Slopes ranged β = 0.69-0.88 and seemed to overlap in the scatter Log plot. The analysis of covariance verified this perception and concluded that lines were parallel. In other words, the allometric function stood for all patients. Values were not different from other studies in humans and pigs. The combination of multislice CT with morphological extraction algorithms was effective to extract allometric functions from coronary arteries in patients and can be easily applied in the clinic.

Abstract: Atherosclerotic plaques form at specific sites of the arterial tree, an observation that has led to the "geometric risk factor" hypothesis for atherogenesis. It is accepted that the location of atherosclerotic plaques is correlated with sites subjected to low abnormal values of wall shear stress (WSS), which is in turn determined by the specific geometry of the arterial segment. In particular, the left coronary artery (LCA) is one of the most important sites of plaque formation and its progression may lead to stroke. However, little is known about hemodynamics and WSS distributions in the LCA. The purpose of this work is to set up a method to evaluate flow patterns and WSS distributions in the human LCA based on real patient-specific geometries reconstructed from medical images.

Abstract: This paper is intended to mention some organizations detailing the type of activities being carried out and the action strategies; to analyze the situation in our country and, finally, to publicize our proposal to this problem. Capitalizing the experience gained in other parts of the world by different entities in order to promote the engineering humanitarian in our country, democratizing access to health, technology and the resources necessary to all the community, we will intend to promote that engineers and engineering students can take a part of the problem both domestically and worldwide, because we are part of the solution and we fit to take charge of the obligations as professionals and human beings.

Abstract: Dr. René Gerónimo Favaloro (12 July 1923 to 29 July 2000) was an Argentinian cardiovascular surgeon who revolutionized the field with his pioneering contributions, the most remarkable being the standardization of the coronary artery bypass surgery, performed for the first time in 1967. This technique, today one of the most commonly performed major operations, improved and saved the lives of countless patients with ischemic heart disease throughout the world and gained him international recognition.

Abstract: The aims were to characterize in muscular arteries (a) the passive and active effects of the adventitia on vessel biomechanical properties and conduit function (CF), and (b) potential differences between the adventitial role in elastic and muscular arteries.

Abstract: The value of mean arterial pressure (MBP) is of clinical importance, and is required for peripheral resistance calculation as well as for central blood pressure calibration procedures. MBP is usually estimated at the upper arm using systolic and diastolic sphygmomanometers pressure values, as 33% of pulse pressure (PP) above diastolic pressure. In a previous work, we proposed to use 38%. The aim of this study was to investigate the validity of the proposed formula to calculate MBP, when assessing subjects with a wide range of blood pressure and pulse wave velocity (PWV) levels. In 73 volunteers (56 ± 10 years, range: 27-82; pulse pressure: 59 ± 12 mmHg, range: 43-86; PWV: 10 ± 2 m/s, range: 8-17) arterial pressure waveforms were obtained at the left brachial artery by applanation tonometry. Diastolic (DBP) and systolic (SBP) brachial pressure were obtained with oscillometric device. Brachial-radial PWV was obtained at the same arm using mechano-transducers. MBP computed as 38% of PP above diastolic pressure, introduces an error of only 0.1% in brachial MBP estimation, independent of pressure and PWV levels.

Abstract: In this present paper, we showed that wavelet analysis (WA) has the potential for extracting specific features from measured arterial diameter and pressure waveforms. The fifth detail of the Daubechies 4 (Db4) wavelet appears to be the most appropriate level for application, in order to analyze artery waveforms and was used to characterized arterial de-endothelization (DE). Raises in smooth muscle tone induced by (DE) tended to increase arterial stiffness and therefore that WA details embed the information of the diameter and pressure pulse that contains the signature of effects of wave travel and reflection affected by arterial stiffness.

Abstract: BACKGROUND: Application of coronary artery calcium (CAC) for stratifying coronary heart disease (CHD) risk may change the proportion of subjects eligible for risk reduction treatment and decrease cost-effectiveness of primary prevention. We therefore aimed to analyze the impact of CAC on CHD risk categorization. METHODS: We measured CAC with electron beam computed tomography in 500 asymptomatic untreated hypercholesterolemic men and re-calibrated 10-year Framingham CHD risk by adding CAC score information (post CAC test risk) via an algorithm integrating relative risk and expected distribution of CAC in the population tested. Proportions of low (<10%), intermediate (10-20%) and high (>20%) risk categories, and of eligibility for lipid-lowering treatment, were compared between Framingham risk and post CAC test risk. RESULTS: In the overall population, post CAC test risk calculation changed risk categorization defined by Framingham assessment alone, with 10% more low risk and 10% less intermediate risk (p<0.01). Risk reclassifications were bidirectional since 30% of high and 30% of intermediate Framingham risk were downgraded to intermediate and low risk categories respectively, while 11% of low and 14% of intermediate Framingham risk were upgraded to intermediate and high-risk categories respectively. Post CAC test risk did not change the proportion of Framingham-based lipid-lowering treatment eligibility in the overall population but decreased it by 8% in intermediate Framingham risk subgroup (p<0.05). CONCLUSIONS: Addition of CAC to risk prediction resulted rather in downgrading than in upgrading risk and did not change treatment eligibility, except in intermediate risk subjects, less frequently eligible for treatment.

Abstract: The early detection of biomechanical modifications in the arterial wall could be used as a predictor factor for various diseases, for example hypertension or atherosclerosis. In this work a transient elastography technique is used for the in vitro evaluation of the arterial wall elasticity. The obtained Young modulus is compared with the one obtained by a more classical approach: pressure-diameter relationships. As a sample an arterial phantom made of PolyVinyl Alcohol (PVA) gel was used. Diameter variation due to pressure variation inside the phantom was recorded by means of ultrasound. Through both techniques similar Young modulus estimations are obtained showing in this way the feasibility of applying transient elastography for the arterial wall elasticity assessment.

Abstract: Type 2 Diabetes Mellitus (DM), or adult-onset diabetes, is being considered as a new pandemic. Cardiovascular disease is the major cause of morbidity and mortality in type 2 DM, due to arterial structure and functional changes. Assessment of arterial structure and biomechanics, by non-invasive methods and parameters, can be used to detect early alterations related to DM. Three markers of vascular disease may help to a better evaluation of vascular dysfunction in type 2 DM patients: carotid intimamedia thickness (IMTc), arterial stiffness, assessed by pulse wave velocity (PWV), and endothelial function, evaluated through the brachial artery flow-mediated dilation (FMD). Among these parameters, IMTc is considered a marker of structural vessel wall properties, and arterial stiffness reflects functional wall properties. Endothelial function represents the arterial way to actively regulate its diameter (smooth muscle-dependent actions) and its visco-elastic properties (wall elasticity and viscosity). IMTc is increased in patients with type 2 DM and other independent risk factors, such as: age, hyperlipidemia and duration of DM. Subjects with DM have shown increased arterial stiffness. Type 2 DM is associated with reductions in FMD (endothelial dysfunction), which has already been reported to be inversely and strongly related to the extent of hyperglycemia. The underlying patho-physiological mechanisms are complex and remain to be fully elucidated. A complete understanding of the association between arterial alterations and early detection, and type 2 DM, may be critical for the primary prevention of DM-related macro-vascular disease.

Abstract: Arterial behavior analysis requires an accurate and dynamic knowledge of the stimuli and reactions involved. Belonging parameters quantification is performed by a data acquisition process and the application of existing models. However, it turns essentially to analyze the adjustment degree of the aforementioned models in terms of the arterial tree. Blood flow behavior as well as wall shear rate and the arterial compliance are anatomic location dependent. The main objective of the present work is to analyze the existing functional relationships between arterial wall and blood flow, in a particular place (brachial artery), in order to asses the specific model applicability, in cases such Poiseuille or Womersley models. In addition, due to the characteristic of the study, gender differential dynamic responses will be evaluated.

Abstract: Current methods used to evaluate the endothelial function have limitations. The analysis of the pulse wave velocity (PWV) response to transient ischaemia could be an alternative to evaluate the endothelial dynamics. Aims: To analyze (a) the carotid-radial PWV temporal profile during flow mediated dilatation test, and (b) the PWV changes considering its main vascular geometrical (diameter) and intrinsic (elastic modulus) determinants. Methods: Sixteen healthy young adults were included. The carotid-radial PWV (strain gauge mechano-transducers), wall thickness and brachial diameter (B-Mode ultrasound) were measured before (basal state), during a forearm cuff inflation (5 minutes) and after its deflation (10 minutes). The PWV, brachial diameter and elastic modulus changes and temporal profile were analyzed (basal state, 15, 30, 45, and 60 seconds after cuff deflation). Results: Transient ischaemia was associated with arterial stiffness changes, evidenced by carotid-radial PWV variations. The PWV and diastolic diameter changes, and temporal profiles differed. The arterial stiffness changes could not be explained only by geometrical (diameter) changes. Conclusion: The carotid-radial PWV analysis, evaluated using robust and simple available techniques, could be used in the clinical practice to study the vascular response to transient ischaemia and the endothelial function.

Abstract: There is evidence that wall shear stress (WSS) is associated with vascular disease. In particular, it is widely accepted that vascular segments with low or oscillatory values of WSS are more probable to develop vascular disease. It is then necessary to establish a realistic model of the blood flow in blood vessels in order to determine precisely WSS. We proposed a numerical 1D model which takes into account the pulsatile nature of blood flow, the elasticity of the vessel, and its geometry. The model allows the calculation of shear stress. It was validated for stationary situations. Then, we computed the time-dependent WSS distribution from experimental data in the sheep thoracic aorta. Results showed that mean WSS calculated through steady flow and rigid walls models is overestimated. Peak WSS values for pulsatile flow must be considered since they resulted to be at least one order higher than mean values. Oscillations in shear stress in a period showed to be approximately of 40%. These findings show that the proposed model is suitable for estimating time-dependent WSS distributions, and confirm the need of using this kind of model when trying to evaluate realistic WSS in blood vessels.

Abstract: Biomechanical and functional properties of tissue engineered vascular grafts must be similar to those observed in native vessels. This supposes a complete mechanical and structural characterization of the blood vessels. To this end, static and dynamic mechanical tests performed in the sheep thoracic and abdominal aorta and the cava vein were contrasted with histological quantification of their main constituents: elastin, collagen and muscle cells. Our results demonstrate that in order to obtain adequate engineered vascular grafts, the absolute amount of collagen fibers, the collagen/elastin ratio, the amount of muscle cells and the muscle cells/elastic fibers ratio are necessary to be determined in order to ensure adequate elastic modulus capable of resisting high stretches, an adequate elastic modulus at low and normal stretch values, the correct viscous energy dissipation, and a good dissipation factor and buffering function, respectively.

Abstract: In several physiological, pathological, and therapeutic circumstances, the arterial blood flow is acutely modified, increasing, in some vascular segments the reversal (SSR) and oscillatory (SSO) components of the shear stress. Recently, in an in vivo model we found a relationship between acute changes in SSR and SSO, and variations in the arterial viscoelasticity. As the arterial viscoelasticity and diameter are the main determinants of the arterial buffering (BF) and conduit (CF) functions, changes in those functions could be expected associated with variations in SSR and SSO. The aim was to analyze the association between acute increases in SSR and SSO, and changes in the aortic CF and BF. Aortic flow, pressure, and diameter were measured in 16 sheep under basal and high reversal and oscillatory flow conditions (high SSR and SSO). Aortic BF and CF were quantified, and their potential association with the SSR and SSO components were analyzed. During high reversal flow rate conditions, a smooth muscle contraction-pattern was evidenced, with an increase in BF and a decrease in CF. Changes in BF and CF were associated with the changes in SSR and SSO. The acute effects on the arterial wall biomechanics of variations in SSR and SSO could contribute to comprehend their chronic effects, and the meaning of the acute vascular effects of changes in SSR and SSO would depend on the situation. Increases in SSR and SSO could be associated with smooth muscle tone increase-dependent changes in arterial BF and CF.

Abstract: Ergometric exercise stress tests (EST) give important information about the cardiovascular (CV) response to increased demands. The expected EST-related changes in variables like blood pressure and heart rate are known, but those in the arterial biomechanics are controversial and incompletely characterized. Aims: a) to characterize the regional and local arterial biomechanical behavior in response to EST, and its temporal profile in the post-EST recovery phase and (b) to compare different arteries biomechanical response to EST. Methods: In 16 non-trained healthy young subjects the carotid-femoral pulse wave velocity and the carotid, femoral and brachial arterial distensibility were non-invasively evaluated before (Rest) and after EST. Post exercise recordings were obtained 0-1, 4-5, and 9-10 minutes after exercise. Results: The EST resulted in an early increase in the arterial stiffness, evidenced by regional and local parameters. There were quali-quantitative differences among the arterial local stiffness response to EST, when analyzing conjunctly the different postEST recovery stages. The biomechanical changes could not be explained only by blood pressure variations.

Abstract: In this paper, we analyze how elastic and viscoelastic properties differ across seven locations along the large arteries in 11 sheep. We employ a two-parameter elastic model and a four-parameter Kelvin viscoelastic model to analyze experimental measurements of vessel diameter and blood pressure obtained in vitro at conditions mimicking in vivo dynamics. Elastic and viscoelastic wall properties were assessed via solutions to the associated inverse problem. We use sensitivity analysis to rank the model parameters from the most to the least sensitive, as well as to compute standard errors and confidence intervals. Results reveal that elastic properties in both models (including Young's modulus and the viscoelastic relaxation parameters) vary across locations (smaller arteries are stiffer than larger arteries). We also show that for all locations, the inclusion of viscoelastic behavior is important to capture pressure-area dynamics.

Abstract:

Abstract: Native vessels-grafts biomechanical mismatch (BM) is related to graft failure. The BM could be reduced using human cryopreserved/defrosted arteries (cryografts), but post-thaw cryografts' recovery could be associated with an impaired biomechanical behavior. In vitro, we demonstrated that our cryopreservation methods do not affect arteries' biomechanics, but only post-implant studies would allow determining the cryografts' biomechanical performance. AIM: To characterize the biomechanical properties of implanted cryografts, and to compare them with cryografts pre-implant, recipients' native arteries, and arteries from subjects with characteristics similar to those of the recipients and multiorgan donors (MOD) whose arteries were cryopreserved. METHODS: Native femoral arteries anastomosed to cryografts, implanted cryografts, and arteries from subjects, recipient-like and MOD-like, were studied. In vitro (pre-implant cryografts) and in vivo non-invasive studies were performed. Arterial pressure, diameter, and wall thickness were obtained to quantify local and regional biomechanical parameters, and to evaluate the arterial remodeling. CONCLUSION: Implanted cryografts were remodeled, with an increased wall thickness, wall-to-lumen ratio, and wall cross-sectional area. The proximal-distal gradual transition in stiffness remained unchanged. Implanted cryografts were stiffer than MOD-like arteries, but more compliant than recipients' arteries. The cryografts-native arteries biomechanical differences were lesser than those described for venous grafts or expanded polytetrafluoroethylene.

Abstract: The cardiac resynchronization therapy (CRT) effects on the arterial load components, the mechanisms (i.e. haemodynamic changes-dependence) involved in the load reduction and the factors (i.e. basal load conditions) associated with the load changes after CRT, are to be evaluated. Aims: a) to analyze the potential changes in the arterial load components (peripheral resistances, arterial compliance and impedance) associated with the CRT, b) to determine if the load components changes are associated with variations in haemodynamic variables (pressure, heart rate or blood flow), c) to analyze the relationship between the load components basal state and their changes after CRT. To fulfill these aims cardiac and arterial structural and mechanical parameters were non-invasively evaluated in 8 heart failure patients, pre- and post-CRT (23+/-8 days). The main results were that short-term after CRT: 1) there were changes in the static and dynamic determinants of the arterial load; 2) the changes in the load components were not associated with heart rate or pressure variations, but with blood flow changes, and 3) the load components basal levels and their changes after CRT were associated.

Abstract: Medical prevention consists to identify as soon as possible apparently healthy individuals who develop a disease and to engage them for active preventive treatment. Several cross-sectional studies of general populations or high cardiovascular risk have shown that coronary calcium score (coronary artery calcium, CAC) was positively associated with traditional risk factors (hypertension, dyslipidemia, diabetes, and smoking) and some new risk factors (fibrinogen). In this work, we first calculated, among 618 men, the risk of 10-years cardiovascular heart disease (CHD) according to the Framingham risk model, and then we calculated the probability that the CAC score of an individual falls in all four CAC categories (0, 1-100, 101-400 and > 400). We obtained risk factors adjusted relative risk (RR) estimates from a meta-analysis comparing the risk of coronary heart disease in individuals with CAC scores of 1-100 (RR = 1.7), 101 - 400 (RR = 3.0) and > 400 (RR = 4.3) with the risk of a person with a CAC score zero. The new model for the risk of CHD for each CAC score category were then calculated assuming an average 1-year risk of CHD and risk assessment of the four CAC score categories, weighted by the probability that scores fall into each category. The combination of modeling the CCA with the modeling of conventional risk factors allows obtaining a remarkable predictive value that can improve the assessment of overall risk Framingham through the reclassification of the risk of CHD to an extent which may be clinically important.

Abstract: The cardiac resynchronization therapy (CRT)effects on the arterial load components, the mechanisms (i.e.haemodynamic changes-dependence) involved in the load reduction and the factors (i.e. basal load conditions) associated with the load changes after CRT, are to be evaluated. Aims: a)to analyze the potential changes in the arterial load components(peripheral resistances, arterial compliance and impedance)associated with the CRT, b) to determine if the load components changes are associated with variations in haemodynamic variables (pressure, heart rate or blood flow), c) to analyze the relationship between the load components basal state and their changes after CRT. To fulfill these aims cardiac and arterial structural and mechanical parameters were non-invasively evaluated in 8 heart failure patients, pre- and post-CRT (23+/-8 days). The main results were that short-term after CRT: 1)there were changes in the static and dynamic determinants of the arterial load; 2) the changes in the load components were not associated with heart rate or pressure variations, but with blood flow changes, and 3) the load components basal levels and their changes after CRT were associated.

Abstract: The geometry of coronary arteries affects regional atherogenic processes. Accurate images can be assessed using multislice computer tomography (MSCT) to estimate bifurcations angles. We propose a three-dimensional (3D) method to measure true bifurcation angles of coronary arteries and to determine possible correlations between plaque presence and angulations. The left main (LM) coronary artery, left anterior descendent (LAD) and left circumflex artery (LCX) were imaged in 40 atherosclerotic and 35 healthy patients, using 64-rows MSCT. This Y-junction was simplified fitting a 3D cylinder to each vessel to estimate true bifurcation angles and diameters. The method was tested in phantoms and interobserver variability was assessed. Geometrical results were compared between groups using an unpaired t-test. The cylinders fitted reasonably well with mean distances to measured points below 0.4 mm. LAD-LCX bifurcation angles were wider in the atherosclerotic group (p < 0.01). LAD (p < 0.01) and LCX (p < 0.05) diameters were also larger. In phantoms mean absolute difference between true and estimated angles (N = 27) was 0.44 +/- 0.54 degrees . Interobserver mean difference (N = 135) was 1.8 +/- 5.8 degrees . Simplifying coronary bifurcation with cylinders results in a reliable technique to assess coronary artery geometry in 3D, avoiding planar projections and decreasing interobserver variability. Geometrical risk factors should be incorporated to properly predict atherosclerosis processes.

Abstract: PURPOSE: Intra-aortic balloon pumping (IABP) may modify arterial biomechanics; however, its effects on arterial wall properties during acute cardio-depression have not yet been fully explored. This dynamical study was designed to characterize the effects of IABP on aortic wall mechanics in an in vivo animal model of acute heart failure. METHODS: Aortic pressure, diameter and blood flow were measured in six anesthetized sheep with acute cardio-depression by halothane (4%), before and during IABP (1:2). Aortic characteristic impedance and aortic wall stiffness indexes were calculated. RESULTS: acute experimental cardio-depression resulted in a reduction in mean aortic pressure (p<0.05) and an increase in the characteristic impedance (p<0.005), incremental elastic modulus (p<0.05), stiffness index (p<0.05) and Peterson elastic modulus (p<0.05). IABP caused an increase in the cardiac output (p<0.005) and a reduction in the systemic vascular resistances (p<0.05). In addition, the aortic impedance, incremental elastic modulus, stiffness index and Peterson modulus were significantly reduced during IABP (p<0.05). CONCLUSIONS: Our findings show that IABP caused changes in aortic wall impedance and intrinsic wall properties, improving the arterial functional capability and the left ventricular afterload by a reduction in both. Systemic vascular resistances and aortic stiffness were also improved by means of smooth muscle-dependent mechanisms.

Abstract: While the situation of tissue donation and transplantation differs between Latin American and European countries, a common problem is tissue deficiency. Hence, at present, there is a pressing need to generate alternatives so as to increase the possibilities of obtaining the requested materials. Consequently, it would be of significant interest to establish an intercontinental network for tissue exchange, to improve international cooperation, and to help patients that need tissue transplantation, and to evaluate the feasibility of using an intercontinental network for the exchange of cryopreserved arteries (cryografts), preserving the arterial distensibility and ensuring a reduced native artery-cryograft biomechanical mismatch. Distensibility was studied in ovine arteries divided into three groups: intact (in vivo tests, conscious animals), fresh control (in vitro tests immediately after the artery excision, Uruguay), and cryografts (in vitro tests of cryopreserved-transported-defrosted arteries, Spain). Histological studies were performed so as to analyze changes in the endothelial layer and elastic components. The comparison between fresh control and cryografts showed that neither the cryopreservation nor the exchange network impaired the distensibility, despite the expected histological changes found in the cryografts. The comparison between intact and cryografts showed that the cryografts would be capable of ensuring a reduced biomechanical mismatch. The cryopreservation and the intercontinental network designed for artery exchange preserved the arterial distensibility. It could be possible to transfer cryografts between Latin America and Europe to be used in cardiovascular surgeries and/or for tissue banking reprocessing, with basic biomechanical properties similar to those of the fresh and/or native arteries.

Abstract: Echographic studies of the composition of atheromatous plaque make use of the median gray level, which provides an overall measure of echogenicity. We propose adding an additional dimension to this approach by dividing the lesion into layers and generating a curve that shows the variation in echolucency with depth.

Abstract: Background: Vascular access (VA) dysfunction is a common cause of hospitalization in chronically hemodialyzed patients (CHP) limiting the improvement in health and has been largely studied in order to decrease the morbidity events that involves both the artery and the vein used in the construction of the fistula. In parallel, patients in end-stage renal failure show an increase in arterial stiffness. Aim: The aims of this work were: (a) to evaluate arterial stiffness through pulse wave velocity (PWV) measurements in the carotid-brachial pathway where the arteriovenous fistulae (AVF) was constructed, and (b) to determine possible differences in arterial stiffness between the carotid-brachial pathway with and without VA. Methods: PWV, clinical and biochemical parameters were measured in 38 CHP. PWV was obtained in the carotid-femoral, and in the left and right carotid-brachial pathway. Results: Carotid-brachial PWV determination in upper limbs with AVF (10.07 +/- ;2.43 m/s) showed significantly lower values than those observed in the contra-lateral arm without VA (11.55 +/- ;2.27 m/s). Curiously, the PWV value observed in arms with an AVF was significantly lower in diabetic than in non-diabetic hemodialyzed patients (NDHP) (8.00 +/- ;2.86 m/s and 10.38 +/- ;2.33 m/s; respectively). Measurements of PWV in the carotid-femoral pathway in CHP showed a mean value of 14.09 +/- ;3.12 m/s. Carotid-femoral PWV in NDHP (14.06 +/- ;2.44 m/s) was significantly lower than that observed in the diabetic patients (16.87 +/- ;3.42 m/s). Conclusions: Carotid-brachial PWV values obtained in the upper limbs, in which VAs were constructed, were significantly lower than that measured in intact arteries in the contra-lateral pathway in CHP.

Abstract: INTRODUCTION AND OBJECTIVES: The incidence of cardiovascular events is related to the sleep-wakefulness cycle. In particular, the magnitude and speed of the changes in hemodynamic variables that occur during transitions between wakefulness and sleep and between sleep and wakefulness are regarded as factors that either predict or determine target organ damage and cardiovascular risk. Although increased arterial stiffness (AS) is associated with the development of cardiovascular abnormalities, it is not known whether there exist any changes in AS that are associated with circadian variations in the incidence of cardiovascular events. The aims of this study were to assess AS in healthy subjects over a 24-hour period, to characterize any differences that occur between sleep and wakefulness, and to investigate any changes in AS that occur during the transition from wakefulness to sleep or from sleep to wakefulness. METHODS: Twenty healthy volunteers with a dipper circadian blood pressure pattern underwent 24-hour ambulatory monitoring of blood pressure, heart rate and AS. In practice, AS was determined using the aorta-brachial pulse transit time and fractional pulsatility indices. Myocardial oxygen consumption was quantified using the double product (DP). An average was calculated for all variables for periods of sleep (23:00 to 06:00) and wakefulness (8:00 to 21:00) and for transitions from wakefulness to sleep (20:00 vs. 02:00) and from sleep to wakefulness (06:00 vs. 10:00 hours). RESULTS: In complete contrast to DP, AS was greater during sleep than wakefulness (P< .05). Moreover, the changes in AS that occurred during transitions from wakefulness to sleep and from sleep to wakefulness were the opposite of those observed in DP (P< .05). CONCLUSIONS: Arterial stiffness was greater during sleep than wakefulness, increased during the transition from wakefulness to sleep, and decreased during the transition from sleep to wakefulness.

Abstract: INTRODUCTION AND OBJECTIVES: The structural and functional changes observed in the left ventricle in professional soccer players could cause alterations in ventricular rotation (Rv) and ventricular torsion (Tv). Our aim was to characterize the changes in Tv that occur in professional soccer players. METHODS: In total, 17 professional soccer players and 10 healthy volunteers who had not undergone training (control subjects) were investigated by M-mode, B-mode and Doppler echocardiography. Left ventricular systolic and diastolic functional and structural parameters were measured. Basal and apical Rv, and Tv were determined using specially developed software (EchoPAC, GE Medical Systems). In addition, Tv was characterized in the time domain. RESULTS: In all subjects, left ventricular structural and functional parameters were within the normal ranges. Both left ventricular ejection fraction and shortening were greater in soccer players (P< .05). The magnitude of apical and basal Rv and the magnitude and velocity of Tv were all lower in soccer players (P< .05). In soccer players, there were negative correlations between the maximum Tv achieved and left ventricular shortening and ejection fraction (P< .05). CONCLUSIONS: The magnitude and velocity of Tv were lower in soccer players. A reduction in Tv might take place under certain physiological conditions and could represent an adaptive response that contributes to increased ventricular efficiency.

Abstract: Intra-aortic balloon pumping (IABP) could modify the arterial biomechanics; however, its effects on arterial wall properties have not been fully explored. This dynamical study was designed to characterize the pressure-dependent and smooth muscle-dependent effects of IABP on aortic wall energetics in an in vivo animal model. Intra-aortic balloon pumping (1:2) was performed in six anesthetized sheep in which aortic pressure and diameter signals were measured in basal, augmented (during balloon inflation), and assisted (postaugmented) beats. Energy dissipation values in augmented and assisted beats were significantly higher than those observed in basal state (p < 0.05). Assisted beats showed a significant increase of wall damping with respect to basal and augmented beats (p < 0.05). Intra-aortic balloon pumping resulted in a significant increase of pulse wave velocity (p < 0.05) in augmented beats with respect to basal state (6.3 +/- 0.8 vs. 5.2 +/- 0.5 m x s(-1)); whereas values observed in assisted beats were significantly (p < 0.05) lower than those observed in augmented beats (4.9 +/- 0.5 vs. 6.3 +/- 0.8 m x s(-1)). Our findings show that IABP determined the pressure and smooth muscle-dependent changes in arterial wall energetics and damping properties in this animal model.

Abstract: AIMS: The intra-aortic balloon pumping (IABP) changes pressure and increases the aorta shear stress reversal (SS(R)) and oscillatory (SS(O)) components. Hence, IABP-dependent changes in aortic biomechanics would be expected, because of vascular smooth muscle (VSM) tone (i.e. flow-induced endothelium-dependent response, related to SS(R) and SS(O) variations) and/or pressure changes. To characterize: (i) the IABP effects on the aortic and global (systemic circulation) biomechanics, analysing their dependence on pressure and VSM basic tone changes and (ii) the relation between the SS(R) and SS(O) and the aortic biomechanical changes associated with the VSM tone variations. METHODS: Aortic flow, pressure and diameter were measured in eight sheep during basal, augmented and assisted beats (1 : 1 and 1 : 2 IABP modalities). Calculations: (i) aortic effective and isobaric elasticity, viscosity, circumferential stress, pulse wave velocity, shear stress and buffer and conduit functions, (ii) peripheral resistance, global compliance, reflection coefficient and wave propagation times and (iii) the relation between SS(R) and SS(O) and biomechanical changes associated with variations in the aortic VSM tone. RESULTS: Augmented and assisted beats showed: global VSM relaxation pattern (reduced peripheral resistance and reflection coefficient; increased propagation times) and local VSM contraction pattern (increased viscosity; reduced diameter, elasticity and circumferential stress), associated with SS(R) and SS(O), levels and changes. The vascular changes reduced the ventricle afterload determinants, increased the vascular buffer performance and kept the conduit capability. CONCLUSION: In addition to pressure-dependent changes, IABP determined biomechanical changes related to variations in the VSM tone. The increased SS(R) and SS(O) were associated with the aortic VSM contraction pattern and biomechanical changes.

Abstract: There is a pressing need to obtain adequate vascular substitutes for arterial by-pass or reconstruction. Since the performance of venous and commercially prosthetic grafts is not ideal and the availability of autologous arteries is limited, the use of cryopreserved arteries has emerged as a very attractive alternative. In this sense, the development of an inter-continental network for cryopreserved tissue exchange would improve international cooperation increasing the possibilities of obtaining the requested materials. In this work, the effects of an inter-continental shipment, which includes cryopreservation, on the biomechanical properties of sheep aortas were evaluated by means of the arterial complex elastic modulus. It is shown that these properties were preserved after the shipment. The actual possibilities of establishing a network for arterial exchange for the international cooperation are discussed.

Abstract: OBJECTIVES: Mechanisms underlying the circadian profile of cardiovascular events (CE) are not totally understood. Whether circadian changes in arterial stiffness (AS) could be related to the circadian profile of CE remains to be investigated. As yet, there is no accepted way to measure circadian profiles or nocturnal-related and/or morning-related changes in cardiovascular variables. The aim of this study was to characterize the circadian pattern and day-night and night-day changes of AS in untreated hypertensive (HG) and healthy subjects (NG), using a recently developed non-symmetrical six-parameter double-logistic model. METHODS: Seven hypertensive and seven normotensive subjects underwent 24 hour ambulatory recordings of blood pressure (BP), heart rate (HR) and aorto-brachial pulse transit time (PTT(AB)) and pulse transit velocity index (PTV(AB)). PTT(AB) and PTV(AB) are inversely and directly related to AS, respectively. The circadian profile and transitional periods (day-night and night-day) were analyzed using a model described by a six-parameter double logistic equation. CONCLUSIONS: The model was adequate to characterize the circadian pattern of AS. We provide the first evidence that AS in humans follows an asymmetric circadian pattern and that this differs between NG and HG. In both NG and HG, AS had a circadian profile, with the highest levels in the night. HG showed larger levels of AS, larger BP variations and rate of change and minor changes in AS during transitional periods.

Abstract: Viscoelastic models can be used to better understand arterial wall mechanics in physiological and pathological conditions. The arterial wall reveals very slow time-dependent decays in uniaxial stress-relaxation experiments, coherent with weak power-law functions. Quasi-linear viscoelastic (QLV) theory was successfully applied to modeling such responses, but an accurate estimation of the reduced relaxation function parameters can be very difficult. In this work, an alternative relaxation function based on fractional calculus theory is proposed to describe stress relaxation experiments in strips cut from healthy human aortas. Stress relaxation (1 h) was registered at three incremental stress levels. The novel relaxation function with three parameters was integrated into the QLV theory to fit experimental data. It was based in a modified Voigt model, including a fractional element of order alpha, called spring-pot. The stress-relaxation prediction was accurate and fast. Sensitivity plots for each parameter presented a minimum near their optimal values. Least-squares errors remained below 2%. Values of order alpha = 0.1-0.3 confirmed a predominant elastic behavior. The other two parameters of the model can be associated to elastic and viscous constants that explain the time course of the observed relaxation function. The fractional-order model integrated into the QLV theory proved to capture the essential features of the arterial wall mechanical response.

Abstract: BACKGROUND: The characterization of the dynamic process of veins walls is essential to understand venous functioning under normal and pathological conditions. However, little work has been done on dynamic venous properties. AIM: To characterize vein compliance (C), viscosity (eta), peak-strain (W St) and dissipated (W(D)) energy, damping (zeta), and their regional differences in order to evaluate their role in venous functioning during volume-pressure overloads. METHODS: In a mock circulation, pressure (P) and diameter (D) of different veins (anterior cava, jugular and femoral; from 7 sheep), were registered during cyclical volume-pressure pulses. From the P-D relationship, C, W(St) and zeta (at low and high P-D levels), eta and W(D) were calculated. RESULTS: For each vein there were P-dependent differences in biomechanical, energetics, and damping capability. There were regional-differences in C, eta), W(St) and W(D) (p<0.05), but not in zeta. CONCLUSION: The regional-dependent differences in dynamics and energetics, and regional-similitude in damping could be important to ensure venous functioning during acute overloads. The lower C and higher W(St) and W(D) found in back-limb veins (femoral), commonly submitted to high volume-pressure loads (i.e. during walking), could be considered relevant to ensure adequate venous system functionality and venous wall protection simultaneously.

Abstract: The aim of this study was to characterize and compare human great saphenous veins (HGSVs), HGSV cryoallografts, expanded polytetrafluoroethylene (ePTFE) segments, and elastic and muscular arteries' biomechanics, so as to identify if the biomechanical coupling and the HGSV advantages with respect to ePTFE depend on the arterial type and/or on the biomechanical property considered. Pressure and diameter were measured in vitro, under arterial hemodynamic conditions, in elastic and muscular arteries, and in vascular substitutes: fresh and cryopreserved HGSV and ePTFE segments. The wall's dynamics (compliance, viscosity, and inertia), energy dissipation, and buffering were calculated. The coupling was quantified for each biomechanical parameter. Cryopreservation preserved HGSV biomechanics. The HGSV cryoallografts' dynamics, energetics, and buffering were lesser with respect to both arteries, but were higher than the ePTFE. The coupling differed, depending on the arterial type and property considered. The biomechanical coupling depended on the artery and property considered. HGSV cryoallograft advantages over ePTFE were arterial type and property independent.

Abstract: Arterial viscoelasticity can be described with a complex modulus (E*) in the frequency domain. In arteries, E* presents a power-law response with a plateau for higher frequencies. Constitutive models based on a combination of purely elastic and viscous elements can be represented with integer order differential equations but show several limitations. Recently, fractional derivative models with fewer parameters have proven to be efficient in describing rheological tissues. A new element, called "spring-pot", that interpolates between springs and dashpots is incorporated. Starting with a Voigt model, we proposed two fractional alternative models with one and two spring-pots. The three models were tested in an anesthetized sheep in a control state and during smooth muscle activation. A least squares method was used to fit E*. Local activation induced a vascular constriction with no pressure changes. The E* results confirmed the steep increase from static to dynamic values and a plateau in the range 2-30 Hz, coherent with fractional model predictions. Activation increased E*, affecting its real and imaginary parts separately. Only the model with two spring-pots correctly followed this behavior with the best performance in terms of least squares errors. In a context where activation separately modifies E*, this alternative model should be considered in describing arterial viscoelasticity in vivo.

Abstract: Recently, it has been proposed the use of speckle-tracking echography (STE) to study the left ventricle (LV) torsion dynamics, which would make LV torsion assessment more available in clinical and research cardiology. LV torsion has been described during exercise and in some sportsmen, but so far, its dynamics has not been studied in soccer players. The aims were to characterize and to compare LV apical and basal rotation, and to analyze LV torsion in professional soccer players using STE, and to determine the main differences in torsion between soccer players and age-matched non-trained individuals. The STE allowed characterizing LV rotation and torsion in both groups. LV torsion level and velocities were lesser in soccer players than in non-trained individuals. Changes in torsion in soccer players could represent physiological adaptations to training.

Abstract: While the effects of increases in forward blood flow on the arterial diameter and elasticity are known, the effects of reversal flow on the arterial properties remain to be characterized. The intra-aortic balloon pumping (IABP), the device most frequently used in circulatory support, acts generating changes in aortic flow (i.e. increasing reversal flow). Recently, in vitro studies showed that flow reversion reduces the endothelial release of relaxing factors. Hence, vascular smooth muscle (VSM) dependent changes in the aortic properties would be expected during IABP. The aim was to analyze the changes in flow during IABP and to characterize the potential effects of reversal blood flow on the aortic biomechanics. Pressure, flow and diameter were measured in sheep, before and during IABP circulatory support. Potential effects of IABP-dependent high reversal flow conditions on viscous and elastic aortic modulus were analyzed, using isobaric analysis. Flow and pressure waveforms were analyzed in the time domain, and the contribution of oscillatory forward and backward waves to the IABP-dependent changes in flow patterns were evaluated. We found that IABP changed mainly diastolic blood flow, with an increase in the reversal flow, secondary to an increase in the oscillatory backward wave amplitude. The acute increase in reversal flow during IABP was associated with vasoconstriction and changes in the aortic mechanics, possibly due to VSM activation.

Abstract: The ideal arterial graft must share identical functional properties with the host artery. Surgical reconstruction of the common carotid artery (CA) is performed in several clinical situations, using expanded polytetrafluoroethylene prosthesis (ePTFE) or saphenous vein (SV) grafts. At date there is interest in obtaining an arterial graft that improves the results of that nowadays available. The use of a fresh or cryopreserved/defrosted artery appears as an interesting alternative. However, if the fresh and cryopreserved/defrosted arteries allow an adequate viscoelastic and functional matching with the host arteries needs to be established. The aims were to compare the viscoelastic and functional performance of: (1) conduits used in CA reconstruction (SV and ePTFE) with those of the fresh and cryopreserved/ defrosted CA and femoral arteries (FA), and (2) normotensive and hypertensive patients' arteries with those of the arterial substitutes in vitro analyzed. Pressure, diameter and wall thickness of the CA were recorded in 15 normotensive and 15 hypertensive patients (in vivo studies), and in SV, fresh and cryopreserved/defrosted CA and FA (obtained from 15 donors), and ePTFE segments (in vitro studies). From stress-strain relationship we calculated elastic and viscous modulus, and the characteristic impedance. The local buffer and conduit functions were quantified as the viscous/elastic quotient and the inverse of the characteristic impedance. Fresh and cryopreserved/defrosted CA and FA were more alike, both in viscoelastic and functional levels, respect to normotensive and hypertensive patients' arteries, than the ePTFE and SV grafts. CA and FA cryografts could be considered an important alternative for carotid reconstruction.

Abstract: Right ventricular adaptation to pulmonary hypertension (PH) is an important prognostic factor. Pulmonary artery (PA) smooth muscle activation attenuates arterial dysfunction during acute PH. We investigated the role of the pulmonary artery vascular smooth muscle activation on the right ventricular-vascular coupling during acute PH. PA flow, pressure, and diameter, right ventricular and aortic pressures were recorded in six anesthetized sheep. Acute PH was induced by phenylephrine (APH) and PA mechanical constriction (PPH). We calculated the PA buffering function, the incremental elastic modulus and pulmonary vascular compliance. Pulmonary vascular impedance and right ventricular hydraulic power were calculated through Fourier approach. We also quantified the magnitude and timing of the reflected wave. Right ventricular-vascular coupling was assessed by the energy transmission ratio. Pulmonary buffering function and vascular compliance increased (P<0.05) and arterial wall stiffness decreased (P<0.05) during APH with respect to PPH. Although total input resistance increased and reflected wave came back earlier during PH states (P<0.05), only PPH produced a rightward shift of the pulmonary impedance and a more prominent reflected wave. Accordingly, APH determined a minor increase of total hydraulic power with a smaller pulsatile to total power ratio and energy transmission ratio (P<0.05). In conclusion, isobaric PA vasoconstriction prevents the pulsatile hydraulic load to increase by preserving the PA buffering function and the reflected wave magnitude. Thus, vascular smooth muscle activation of the main PA improves the energy transfer from the right ventricle to the hypertensive pulmonary circulation, and this may play relevant role in the right ventricular adaptation to acute PH.

Abstract: The causes of the regional differences in venous grafts patency rates are partially understood. Differences in vein dynamics during physiological situations could determine differences in veins' capability to face arterial conditions and could contribute to the dissimilar performance of veins as arterial grafts. In vitro pressure and diameter were measured in four different veins during physiological and arterial (graft) pressure conditions. A diameter-pressure transfer function was designed. Compliance, viscous and inertial properties; circumferential stresses and deformation; and buffering function were calculated. Regional differences in veins' dynamics, but not in buffering function were found during physiological and arterial conditions. The back vein (femoral) showed the least changes when submitted to arterial conditions. Arterial conditions represent different changes in vein dynamics depending on the segment considered. The regional differences in vein dynamics, both at physiological and graft conditions, could contribute to explain the dissimilar results of venous grafts.

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Abstract: INTRODUCTION AND OBJECTIVES: Ventricular dynamic afterload depends on arterial viscoelastic and geometric properties. Vasoactive factors produced in the adventitia modulate arterial tone. However, it is still not known whether the adventitia is involved in determining the magnitude of the dynamic afterload. The aim of this study was to investigate the role played by the adventitia, via smooth muscle-dependent mechanisms, in determining dynamic afterload. METHODS: The diameter, pressure and flow in brachiocephalic trunks from sheep were measured before and after removal of the adventitia, both in vivo with muscular reactivity preserved (n=8) and in vitro with muscular reactivity abolished (n=8). All studies were performed under similar hemodynamic conditions. Dynamic afterload was determined from elastic and viscous arterial responses, elastic and viscous work, arterial characteristic impedance, and pulse wave velocity. Comparison of in vivo and in vitro findings enabled smooth muscle-dependent changes to be evaluated. RESULTS: Only in vivo, did removal of the adventitia lead to a reduction in vessel diameter (17.32 [2.02] vs 15.46 [1.28] mm) and to increases in elastic (7.21 [1.39] vs 15.59 [3.00] x 10(6) dyn.cm(-2)) and viscous (5.16 [2.04] vs 9.87 [2.00] x 10(5) dyn.s.cm(-2)) arterial responses, elastic (6.15 [1.08] vs 9.20 [0.76] x 10(-2) J/m2) and viscous work (11.61 [2.25] vs 15.20 [2.37] x 10(-3) J/m2), impedance (223.97 [136.11] vs 396.33 [182.27] dyn x s x cm(-3)), and pulse wave velocity (397.70 [31.21] vs 598.78 [28.04] cm.s(-1)) (P<.05). The reduction in diameter and the increases in elastic and viscous responses are evidence of muscular activation. CONCLUSIONS: The adventitia may contribute to the control of ventricular dynamic afterload by means of mechanisms dependent on muscular tone.

Abstract: Each artery conduces blood (conduit function, CF) and smoothes out the pulsatility (buffering function, BF), while keeping its wall protected against the high oscillations of the pulse waves (damping function, ksi). These functions depend on each segment visco-elasticity and capability to store and dissipate energy. When a graft/prosthesis is implanted, the physiological gradual transition in the visco-elasticity and functionality of adjacent arterial segments is disrupted. It remains to be elucidated if the cryografts would allow keeping the physiological biomechanical transition. Aim: to evaluate the cryografts capability to reproduce the functional, energetic and reflection properties of patients' arteries and fresh-homografts. Common carotid's pressure, diameter and wall-thickness were recorded in vivo (15 patients) and in vitro (15 cryografts and 15 fresh-homografts from donors). Calculus: elastic (E(pd)) and viscous (V(pd)) indexes, CF, BF, dissipated (W(D)) and stored (W(PS)) energy and ksi. The graft-patient's artery matching was evaluated using the reflection coefficient (gama) and reflected power (W(gama)). Cryografts did not show differences in E(pd), V(pd), BF, CF, W(D), W(PS), and ksi, respect to fresh-homografts and patients' arteries, ensuring a reduced gama and W(gama). Cryografts could be considered alternatives in arterial reconstructions since they ensure the gradual transition of patients' arteries biomechanical and functional behavior.

Abstract: INTRODUCTION: The prosthesis nowadays used in the vascular access for haemodialysis have low patency rates, mainly due to the luminal obstruction, determined by the intimal hyperplasia. Several factors have been related to de development of intimal hyperplasia and graft failure. Among them are the differences in the biomechanical properties between the prosthesis and the native vessels. In the searching for vascular prosthesis that overcomes the limitations of the currently used, the cryopreserved vessels (cryografts) appear as an alternative of growing interest. However, it is unknown if the mechanical differences or mismatch between prosthesis and native vessels are lesser when using cryografts. OBJECTIVE: To characterize and compare the biomechanical behaviour of native vessels used in vascular access and cryografts. Additionally, segments of expanded polytetrafluoroethylene (ePTFE) were also evaluated, so as to evaluate the potential biomechanical advantages of the cryografts respect to synthetic prosthesis used in vascular access. METHODS: Segments from human humeral (n = 12), carotid (n = 12) and femoral (n = 12) arteries, and saphenous vein (n = 12), were obtained from 6 multiorgan donors. The humeral arteries were studied in fresh state. The other segments were divided into two groups, and 6 segments from each vessel were studied in fresh state, while the remaining 6 segments were evaluated after 30 days of criopreservation. For the mechanical evaluation the vascular segments and 6 segments of ePTFE were mounted in a circulation mock and submitted to haemodynamic conditions similar to those of the in vivo. Instantaneous pressure (Konigsberg) and diameter (Sonomicrometry) were measured and used to calculate the viscous and elastic indexes, the compliance, distensibility and characteristic impedance. For each mechanical parameter studied, the mismatch between the prosthesis and the native vessel was evaluated. RESULTS: The ePTFE was the prosthesis with the higher mechanical mismatch (p < 0.05). The venous and arterial cryografts showed the least mismatch with native veins and arteries, respectively. The prosthesis with the least mechanical mismatch was different, depending on the native vessel evaluated, and for a native vessel, on the parameter considered. CONCLUSION: The mechanical mismatch between the native vessel and the vascular prosthesis used in a vascular access could be reduced using cryografts.

Abstract: The viscoelastic and inertial properties of the arterial wall are responsible for the arterial functional role in the cardiovascular system. Cryopreservation is widely used to preserve blood vessels for vascular reconstruction but it is controversially suspected to affect the dynamic behaviour of these allografts. The aim of this work was to assess the cryopreservation's effects on human arteries mechanical properties. Common carotid artery (CCA) segments harvested from donors were divided into two groups: Fresh (n = 18), tested for 24-48 h after harvesting, and Cryopreserved (n = 18) for an average time of 30 days in gas-nitrogen phase, and finally defrosted. Each segment was tested in a circulation mock, and its pressure and diameter were registered at similar pump frequency, pulse and mean pressure levels, including those of normotensive and hypertensive conditions. A compliance transfer function (diameter/pressure) derived from a mathematical adaptive modelling was designed for the on line assessment of the arterial wall dynamics and its frequency response. Assessment of arterial wall dynamics was made by measuring its viscous (eta), inertial (M) and elastic (E) properties, and creep and stress relaxation time constant (tauC and tauSR, respectively). The frequency response characterization allowed to evaluate the arterial wall filter or buffer function. Results showed that non-significant differences exist between wall dynamics and buffer function of fresh and cryopreserved segments of human CCA. In conclusion, our cryopreservation method maintains arterial wall functional properties, close to their fresh values.

Abstract: Damping is the conversion of mechanical energy of a structure into thermal energy, and it is related to the material viscous behavior. To evaluate the role of damping in the common carotid artery (CCA) wall in human hypertension and the possible improvement of angiotensin-converting enzyme (ACE) inhibition, we used noninvasive CCA pressure (tonometry) and diameter (B-mode echography) waveforms in normotensive subjects (NT group; n=12) and in hypertensive patients (HT group; n=22) single-blind randomized into HT-placebo (n=10) or HT-treated (ramipril, 5 to 10 mg/d during 3 months; n=12). Vascular smooth muscle (VSM) null tonus condition was achieved from in vitro pressure and diameter waveforms (Konigsberg microtransducer and sonomicrometry) measured in explanted human CCA (n=14). Arterial wall dynamics was described by viscous (eta), inertial (M), and compliance (C) parameters, mean circumferential wall stress, viscous energy dissipation (WD), peak strain energy (WSt), damping ratio (xi=WD/WSt), and modeling isobaric indexes CIso and WSt(Iso). The lack of VSM tonus isobarically increased wall stress and reduced eta, CIso, and damping (P<0.01). Wall stress, eta, and WD were greater in HT than in NT (P<0.015) and arrived near normal in HT-treated (P<0.032 respect to HT), with no changes in HT-placebo. Whereas CIso increased in HT-treated (P<0.01) approaching the NT level, xi did not vary among groups. During hypertension, because of the WSt increase, the arterial wall reacts increasing WD to maintain xi. ACE inhibition modulates VSM activation and vessel wall remodeling, significantly improving wall energetics and wall stress. This protective vascular action reduces extra load to the heart and maintains enhanced arterial wall damping.

Abstract: Arteries are viscoelastic materials. Viscoelastic laws are fully characterized by measuring a complex modulus. Arterial mechanics can be described using stress-strain dynamic measurements applied to the particular cylindrical geometry. Most materials show an energy loss per cycle that increases steadily with frequency. By contrast, the frequency modulus response in arteries presents a frequency independence describing a plateau above a corner frequency near 4Hz. Traditional methods to fit this response include several spring and dashpot elements to model integer order differential equations in time domain. Recently, fractional derivative models proved to be efficient to describe rheological tissues, reducing the number of parameters and showing a natural power-law response. In this work a fractional derivative model with 4-parameter was selected to describe the arterial wall mechanics in-vivo. Strain and stress were measured simultaneously in an anaesthetized sheep. A fractional model was applied. The order resulted alpha=0.12, confirming the manifest elastic response of the aorta. The fractional derivative model proved to naturally mimic the elastic modulus spectrum with only 4 parameters and a reasonable small computational effort.

Abstract: AIM: An adventitia dependent regulation of the vascular smooth muscle tone has been described. However, if the adventitia plays an active role on arterial wall biomechanical behaviour and functions remains to be established. Our aim was to characterize the influence of adventitia on arterial wall mechanical properties and the arterial conduit and buffer functions. METHODS: Ovine brachiocephalic arteries were studied in vivo (n = 8) and in vitro (with null tone) in a circulation mock (n = 8). Isobaric, isoflow and isofrequency studies were performed. In each segment, pressure and diameter waves were assessed before and after adventitia removal. From the arterial stress-strain relationship, we derived the elastic and the viscous modulus. The buffering and conduit functions were calculated using the Kelvin-Voigt's time constant and the inverse of the characteristic impedance, respectively. RESULTS: In in vivo studies arterial diameter decreased after adventitia removal (P < 0.05). Elastic and viscous modulus in in vivo studies were significantly higher in adventitia-removed arteries, compared with values in intact vessels (P < 0.05). This behaviour was not observed in in vitro experiments. An impairment of buffer and conduit functions was observed in vivo after adventitia removal (P < 0.05), while both functions remain unchanged in in vitro studies (P > 0.05). CONCLUSIONS: Arterial wall viscosity and elasticity were influenced by adventitia removal in in vivo studies, possibly by a smooth muscle-dependent mechanism, since it was not present in in vitro experiments. Adventitia would be involved in a physiological mechanism of arterial wall viscous and elastic properties regulation, that could influence arterial buffering and conduit functions.

Abstract: Factors that explain the different results among veins, and causes of the superior performance of vein grafts for small arterial reconstructions, remain unclear. The aim was to compare the biomechanical behavior of veins and arteries from different regions and sizes under arterial conditions. In vitro pressure and diameter were measured in four different veins and three different ovine arteries. A diameter-pressure transfer function was designed, and compliance, viscous, and inertial indexes, and viscous energy and buffering function were calculated. Regional differences in vein mechanical behavior and energy dissipation were found. Veins and arteries vary in mechanical properties and buffering, but the differences were lesser when considering the smallest artery. The differences among veins' viscosity, compliance, and energy dissipation, but not in the buffering capability, could be related to different performances of veins when used as arterial grafts. The major biomechanical matching could contribute to explain veins with better results in small arteries reconstruction.

Abstract: The surgical options in arterial reconstruction are: the use of autologous arteries; autologous veins; or expanded polytetrafluoroethylene (ePTFE) grafts. However, the development of intimal hyperplasia when using veins or ePTFE grafts has been associated with graft failure. Since autologous arteries are not always available, the use of cryopreserved arteries has to be considered. The aims of this study were: (a) to compare the viscoelastic properties of stored cryopreserved arteries and fresh arteries by in vitro analysis; and (b) to compare the viscoelastic properties of arteries measured non-invasively in normotensive patients, with fresh arteries, cryopreserved arteries, and ePTFE segments. The viscoelastic studies were performed in normotensive patients using stress-strain analysis with non-invasive measurement of pressure and diameter in the common carotid artery, and in vitro measurements of pressure and diameter in arteries and prostheses. The in vitro studies showed that the elastic modulus (E), viscous modulus (eta), Stiffness Index (SI), Peterson modulus (Ep), and the pulse wave velocity (PWV) values for human cryopreserved carotid arteries were similar to the values obtained non-invasively in normotensive subjects (P>0.05) and to human fresh vessels (P>0.05). In vitro, the SI, Ep, PWV, and E values of ePTFE were significantly higher than the observed values in subjects and with fresh and cryopreserved arteries (P<0.05); on the other hand the ePTFE eta values were the lowest (P<0.05). We concluded that cryopreserved arteries have similar viscoelastic properties to those obtained in vivo in the arteries of normotensive subjects and in vitro in fresh arteries. Consequently, we conclude that the cryopreservation procedure does not modify the mechanical properties of the arterial wall.

Abstract: INTRODUCTION AND OBJECTIVES: It is not yet known whether cryopreservation enables vessels to retain their viscoelastic properties or whether cryopreserved homografts are biomechanically more like native arteries than currently used vascular prostheses. The study objectives were: a) to determine whether our cryopreservation methodology enables arterial and venous homografts to retain their viscoelastic and functional properties; and b) to assess similarities between patients' femoral arteries, homografts, and other vascular prostheses in common use. METHODS: The pressure and the diameter and parietal thickness of 15 muscular (femoral) arteries were measured in patients using tonometry and echography, both noninvasive techniques. In addition, the pressure in and diameter and parietal thickness of 15 fresh and 15 cryopreserved human muscular (femoral) artery segments, saphenous veins, and 15 expanded polytetrafluoroethylene (ePTFE) vascular prostheses were measured in vitro under hemodynamic conditions similar to those in patients. A Kelvin-Voigt model of the segment wall was used to derive elastic (Epd, mm Hg/mm) and viscous (Vpd, mm Hg x s/mm) pressure-diameter indices, the buffering function (Vpd/Epd), and the conduit function (1/Zc, where Zc is the characteristic impedance). The incremental Young modulus, the pressure-strain elastic modulus, and pulse wave velocity were also calculated. RESULTS: No difference was observed between either the viscoelastic or functional properties of fresh and cryopreserved homografts. Arterial homografts were the most similar to the patient's arteries. CONCLUSIONS: Cryopreservation enabled venous and arterial homografts to retain their viscoelastic and functional properties. Of all the grafts investigated, arterial homografts were most similar, both biomechanically and functionally, to the patient's femoral arteries.

Abstract: The aim was to evaluate our cryopreservation method effects on the mechanical properties and filtering function of human superficial femoral arteries (SFA). SFA segments from 10 multiorgan donors were divided into two groups: fresh, tested 24-48 h after harvesting, and cryopreserved/defrosted, tested after 1 month of cryopreservation. The cooling process was carried out in three steps: 2 degrees C/min until -40 degrees C; 5 degrees C/min until -90 degrees C and finally a rapid cooling by transferring the bag to vapour phase of liquid nitrogen (-142 degrees C). Thawing was made in two steps, a slow warming time by exposing the bag to 20 degrees C during 20 min, followed by a rapid warming by immersion in a 40 degrees C warm bath until defrost. In a circulation mock, arterial pressure [Pressure signal (P)] and diameter [Diameter (D)] were registered at similar stretch-frequency, P and flow levels. A compliance transfer function (D/P) was used for the on-line assessment of the arterial wall elastic (E), viscous (eta), and inertial (M) properties. To evaluate the arterial wall filter function, the arterial wall D/P frequency response was characterized, the cut-off frequency (fc) was quantified, and the viscous energy dissipation (Weta) was calculated. After cryopreservation, there were not significant changes in E, eta, M, Weta, and fc.

Abstract: BACKGROUND: Wall shear stress, arterial wall elasticity, and intimal hyperplasia are related. The aim of this study was to investigate the in vitro mechanical properties of ovine femoral arteries, jugular veins, and expanded polytetrafluoroethylene conduits, and to evaluate postoperative intimal hyperplasia. METHODS: Arterial, venous, and ePTFE mechanical properties were studied in a circulating loop at isobaric systemic pressures. Histological studies of intimal hyperplasia in ePTFE-bypassed femoral arteries with and without Miller cuffs were performed at the 40th and 120th day. RESULTS: The incremental elastic modulus of veins was significantly higher than that of femoral arteries (P < 0.05), but significantly lower than that of ePTFE graft conduits (P < 0.05). Intimal hyperplasia was significantly less in Miller-cuff-bypassed arteries both at the 40th and 120th day (P < 0.01). CONCLUSIONS: The Miller cuff acts as a mechanical adapter enhancing wall shear stress and the elastic matching between ePTFE and the native artery, resulting in an early decrease of intimal hyperplasia.

Abstract: The Favaloro University initiated the academic path in biomedical sciences in Buenos Aires, Argentina. As a very promising area, the biomedical world offers the integration between several domains, complementing medicine with engineering topics. The profile of the graduated students proved to be very versatile, allowing their instantaneous incorporation to the competitive market in this vast field. The university strategy is to concentrate basic science in the first 3 years and add the specific biological/medical concepts in the last 2 years. The students achieve a bachelor degree that integrates their knowledge in basic sciences. Afterwards, they attend a professional 2 year cycle, choosing between biomedical, physics and medical computing branches. The results proved to be effective in terms of professional and academic quality, market insertion and even the creation of promising seeds for future enterprises.

Abstract: INTRODUCTION AND OBJECTIVES: Regional variations in the incidence of vascular diseases have been related to regional differences in arterial viscoelasticity. The aim of this study was to characterize the differences in the elastic and viscous modulus and in wall buffering function between central and peripheral systemic arteries, through a time-series analysis of the pressure-diameter relationship. MATERIAL AND METHOD: Pressure and diameter were measured in seven arterial segments (carotid, brachiocephalic trunk, ascending aorta, proximal, middle and distal descending thoracic aorta, and femoral artery) from six sheep. Each segment was mounted on an in vitro mock circulatory system and perfused with Tyrode solution, with a pulse frequency of 1.8 Hz and systemic pressure levels. We used the Kelvin-Voigt model to calculate the pressure-diameter elastic (Epd, mmHg/mm) and viscous (Vpd, mmHg.s/mm) modulus, and to quantify the local wall buffering function (Vpd/Epd). We also calculated the incremental Young's and pressure-strain elastic modulus and pulse wave velocity for each segment. RESULTS: The elastic and viscous modulus increased from proximal to distal segments. The wall buffering function did not differ significantly between arteries. The lower rigidity of the central arteries compared to the distal ones may indicate that the systolic arterial compliance function is concentrated in the central arterial segments. On the other hand, the greater viscosity in the distal segments may indicate that viscous energy loss is concentrated in these segments. CONCLUSIONS: Arterial elasticity and viscosity can be interpreted as properties that are dependent on the region of the vessel, whereas wall buffering function can be considered region-independent.

Abstract: Acute pulmonary hypertension (PH) may arise with or without an increase in vascular smooth muscle (VSM) tone. Our objective was to determine how VSM activation affects both the conduit (CF) and wall buffering (BF) functions of the pulmonary artery (PA) during acute PH states. PA instantaneous flow, pressure, and diameter of six sheep were recorded during normal pressure (CTL) and different states of acute PH: 1) passively induced by PA mechanical occlusion (PPH); 2) actively induced by intravenous administration of phenylephrine (APH); and 3) a combination of both (APPH). To evaluate the direct effect of VSM activation, isobaric (PPH vs. APH) and isometric (CTL vs. APPH) analyses were performed. We calculated the local BF from the elastic (EPD) and viscous (etaPD) indexes as etaPD/EPD and the characteristic impedance (ZC) from pressure and flow to evaluate CF as 1/ZC. We also calculated the absolute and normalized cross-sectional pulsatility (PCS and NPCS, respectively), the dynamic compliance (CDYN), the cross-sectional distensibility (DCS), and the pressure-strain elastic modulus (EP). The isobaric analysis showed increase of CF, BF, and etaPD (P < 0.01) and decrease of EPD (P < 0.05) during APH in respect to PPH (concomitant with isobaric VSM activation-induced vasoconstriction, P < 0.01). The isometric analysis showed increase of E(PD) and etaPD (P < 0.01), nonsignificant difference in BF (even in the presence of a significant mean PA pressure rise, from 14 (SD 6) to 25 (SD 8) mmHg, P < 0.01), and decrease in CF (P < 0.01) during APPH respect to CTL. Mechanical occlusions (PPH and APPH) reduced BF (P < 0.01) and increased EPD (P < 0.05) with regard to their previous steady states (CTL and APH). Nonsignificant differences were found in EPD between PPH and APPH. VSM activation (APH and APPH) increased etaPD (P < 0.01) respect to their previous passive states (CTL and PPH), but no significant differences were found within similar levels of VSM activation. In conclusion, VSM plays a relevant role in main pulmonary artery function during acute pulmonary hypertension, because isobaric vasoconstriction induced by VSM activation improves both BF and CF, mainly due to the increase in etaPD concomitant with the arterial compliance. CDYN and DCS were the more pertinent clinical indexes of arterial elasticity. Additionally, the etaPD-mediated preservation of the BF could be evaluated by the geometric related indexes (PCS and NPCS), which appear to be qualitative markers of arterial wall viscosity status.

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Abstract: The viscoelastic properties of the arterial wall are responsible for their functional role in the arterial system. Cryopreservation is widely used to preserve blood vessels for vascular reconstruction but is controversially suspected to affect the dynamic behaviour of these allografts. The aim of this study was to determine whether differences in the dynamic behaviour exist or not between fresh and cryopreserved human common carotid arteries (CCA). Using a previously developed mock circulation system, dynamic pressure-diameter tests were performed on segments of human fresh (n=10) and cryopreserved arteries (n=7). A diameter-pressure transfer function was designed to evaluate the wall dynamics. An adaptive model was fit to obtain its frequency response. Three models were tested. Results show that non-significant differences exist between wall dynamics of fresh and cryopreserved segments of human CCA.

Abstract: AIM: We determined the wall mechanical response of the pulmonary artery (PA) to acute pulmonary hypertension induced pharmacologically and by an occlusion maneuver, to study the vascular response of the local segment and its influence in the whole pulmonary circulation. METHODS: Pulmonary pressure and diameter were measured in six anaesthetized sheep under steady-state conditions. Transient hypertension in the PA was induced by phenylephrine (PHE) and a high pressure (HP) mechanical occlusion aimed at producing the same pulse and mean pressure responses. A viscoelastic arterial wall model was applied and the elastic (E(pd)) and viscous (micro) indexes were obtained. The micro/E(pd) ratio was adopted to quantify the damping performance of the arterial wall segment. The diastolic time constant was used as an indicator of the whole pulmonary buffering function. The systemic pressure was always measured. RESULTS: The pulmonary mean, systolic and pulse pressure increases (P < 0.05) were similar during PHE and HP, with respect to control. PHE also induced a systemic pressure rise (P < 0.05). The E(pd) elastic index increased during HP (P < 0.05) and tended to increase during PHE with respect to control. The viscous index micro only increased with PHE (P < 0.05) with respect to control and occlusion. The diastolic time constant increased with PHE with respect to control (P < 0.05). CONCLUSIONS: A pressure rise in the PA, induced by an occlusion maneuver, increased local stiffness. Similar pressure rises with smooth muscle activation (PHE), produced both a stiffness and viscous index increase. In PHE resistance increases more than compliance decreases so that the global net effect is a longer decay time. Smooth-muscle activation enhances the local damping effect (micro/E(pd)), concomitant with the buffering function improvement.

Abstract: Compliance is not linear within the physiological range of pressures, and linear modeling may not describe venous physiology adequately. Forearm and calf venous compliance were assessed in nine subjects. Venous compliance was modeled by using a biphasic model with high- and low-pressure linear phases separated by a breakpoint. This model was compared with a linear model and several exponential models. The biphasic, linear, and two-parameter exponential models best represented the data. The mean coefficient of determination for the biphasic model was greater than for the linear and exponential models in the calf (biphasic 0.94 +/- 0.04, exponential 0.81 +/- 0.16, P = not significant; and linear 0.54 +/- 0.05, P < 0.05) and forearm (biphasic 0.83 +/- 0.17, exponential 0.79 +/- 0.15, P = not significant; and linear 0.51 +/- 0.06, P < 0.05). The breakpoint pressure in the biphasic model was higher in the calf than the forearm, 34.4 +/- 3.9 vs. 29.1 +/- 4.5 mmHg, P < 0.05. A biphasic model can describe limb venous compliance and delineate differences in venous physiology at high and low pressures. The steep low-pressure phase of the compliance curve extends to higher pressures in the calf than in the forearm, thereby enlarging the range of pressures over which hemodynamic regulation by the calf venous circulation occurs.

Abstract: The goal of this study was to determine the in vivo pulmonary arterial buffering function (BF) during acute and moderate pulmonary hypertension achieved by phenylephrine-induced smooth muscle activation. Pulmonary pressure (Konigsberg P7) and diameter (sonomicrometry) were measured in nine anesthetized sheep. Transit pulmonary arterial hypertension was induced by mechanical occlusion of the pulmonary artery (HP) and by phenylephrine infusion (5 microg/kg/min) (PHE). A viscoelastic Kelvin-Voigt model was used. By increasing the values of the viscous modulus, the pressure-diameter hysteresis area was reduced to a minimum in order to obtain the purely elastic pressure-diameter relationship. The elastic index (E) was calculated as the first derivative of the exponential model of the purely elastic pressure-diameter relationship at the mean pressure point. Systolic, diastolic, mean and pulse pressures were similar during HP and PHE, but significantly higher with regard to control steady state. In HP, E and arterial diameter (both its minimum and maximum values) increased significantly. In contrast, when pulmonary hypertension was induced by VSM activation, E was maintained concomitantly with pulmonary artery vasoconstriction. Pulmonary hypertension produced by occlusion of the pulmonary artery increases elasticity. Smooth muscle activation may offset the deleterious effect of pulmonary hypertension on arterial wall elasticity by reducing E and impeding arterial dilatation and collagen recruitment, maintaining BF during pulmonary hypertension.

Abstract: INTRODUCTION AND OBJECTIVES: To characterize the viscoelastic properties of the aorta and pulmonary arteries and the effects of vascular smooth muscle activation on arterial buffering function. MATERIAL AND METHOD: Aortic and pulmonary artery pressure and diameter were measured in six anesthetized sheep under baseline conditions, and during arterial hypertension induced by mechanical vascular occlusion (passive), and i.v. phenylephrine (active). Arterial wall elasticity and viscosity were calculated, and buffering function was characterized: a) locally as the viscosity/elasticity ratio, and b) globally for each circuit, as the time-constant of ventricular relaxation. RESULTS: Viscoelasticity was higher in the aorta than in the pulmonary artery (p < 0.05), however, parietal buffering function was similar in both. Global buffering function was highest in the systemic circuit (p < 0.05). During passive hypertension, elasticity was significantly increased with no change in viscosity; this led to a significant reduction in local buffering function, and in global buffering function in each circuit. During active hypertension, viscosity increased (p < 0.05), while local and global buffering functions returned to baseline values. CONCLUSIONS: The viscosity/elasticity ratio was higher in the aorta than in the pulmonary artery, and arterial wall buffering function was similar in both vessels. Systemic global buffering function was higher than pulmonary circuit buffering function. Elasticity depends on intravascular pressure, whereas viscosity is a marker of the degree of smooth muscle activation. Smooth muscle activation may benefit the cardiovascular system by maintaining local and global buffering functions.

Abstract: AIM: To characterize the buffering function of the pulmonary artery in vivo and to determine the role of vascular smooth muscle (VSM) activation in vessel wall elasticity. MATERIAL AND METHOD: Pulmonary artery pressure and diameter were measured in 9 anesthetized sheep. Pulmonary artery hypertension was induced by mechanical occlusion of the pulmonary artery and by phenylephrine infusion (5 microg/kg/min) (PHE). Once the pressure-diameter loop was obtained, hysteresis was reduced to a minimum by increasing the modulus of viscosity. Elasticity was calculated as the first derivative of mean diastolic pressure assuming a purely elastic relation. Pulse wave velocity (PWV) and time constant (tau) were also obtained. RESULTS: Systolic, diastolic, mean and pulse pressures were similar during pulmonary artery hypertension and PHE infusion, but significantly higher in comparison to baseline conditions. Elasticity and diameter of the pulmonary artery increased significantly. In contrast, during VSM activation elasticity remained unchanged and diastolic diameter was reduced. PWV increased during both pulmonary artery hypertension and PHE infusion (p < 0.05); however, the increase during PHE infusion was smaller (15%) than during induced hypertension (33%). tau was significantly reduced during hypertension, but did not change during VSM activation. CONCLUSIONS: VSM activation may offset the deleterious effect of pulmonary artery hypertension on arterial wall stiffness by reducing elasticity and PWV. The VSM may modulate the Windkessel function in the pulmonary artery, preserving elasticity indexes during pulmonary artery hypertension.

Abstract: The role of blood viscosity on arterial wall elasticity before and after deendothelization (DE) was studied. Seven ovine brachiocephalic arteries were studied in vitro under physiological pulsatile flow conditions achieved by a mock circulation loop. Instantaneous pressure and diameter signals were assessed in each arterial segment. Incremental elastic modulus (E(inc)) was calculated using the slope of the pure elastic stress-strain relationship. There was no significant difference between E(inc) values before and after DE (3.11 vs. 3.16 10(7) dyn/cm(2)) at a blood viscosity of 2.00 mPa. s. Increases in blood viscosity (2.50, 3.00, 3.50, and 4.00 mPa. s) always resulted in decreases of E(inc) before DE; inversely, increases in blood viscosity resulted in increases of E(inc) after DE. These values of E(inc), for identical levels of blood viscosity, were always significantly lower (P < 0.05) before DE than those obtained after DE. Arterial wall elasticity assessed through E(inc) was strongly influenced by blood viscosity, probably due to presence or absence of endothelium relaxing factors or to direct shear smooth muscle activation when endothelial cells are removed.

Abstract: Viscoelastic properties determine the dynamic behaviour of the arterial wall under pulsatile pressure and flow, suggesting time- or frequency-dependent responses to changes in wall stress and strain. The objectives of the present study were: (i) to develop a simplified model to derive simultaneously the elastic, viscous and inertial wall moduli; (ii) to assess Young's modulus as a function of frequency, in conscious, chronically instrumented dogs. Parametric discrete time models were used to characterise the dynamics of the arterial system based on thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements in control steady state and during activation of smooth muscle with the alpha-adrenoceptor agonist phenylephrine (5 microg kg(-1) min(-1), I.V.), in eight conscious dogs. The linear autoregressive model and a physically motivated non-linear model were fitted to the input-output (stress-strain) relationship. The aortic buffering function (complex Young's modulus) was obtained in vivo from the identified linear model. Elastic, viscous and inertial moduli were significantly increased from control state ((44.5 +/- 7.7) x 10(4) Pa; (12.3 +/- 4.7) x 10(4) Pa s; (0.048 +/- 0.028) x 10(4) Pa s(2) ) to active state ((85.3 +/- 29.5) x 10(4) Pa, P < 0.001; (22.4 +/- 8.3) x 10(4) Pa s, P < 0.05; (0.148 +/- 0.060) x 10(4) Pa s(2), P < 0.05). These moduli, obtained using the linear model, did not present significant differences compared with those derived using the non-linear model. In control conditions, the magnitude of the normalised complex Young's modulus was found to be similar to that reported in previous animal studies ranging from 1 to 10 Hz. During vascular smooth muscle activation, this modulus was found to be increased with regard to control conditions (P < 0.01) in the frequency range used in this study. The frequency-dependent Young's modulus of the aortic wall was obtained for the first time in conscious, unsedated dogs. The parametric modelling approach allows us to verify that vascular smooth muscle activation increases the elastic, viscous and inertial moduli with the advantage of being able to track their time evolution. Furthermore, under activation, the aortic wall remains stiff in the physiological frequency range, suggesting the impairment of the arterial buffering function. Experimental Physiology (2001) 86.4, 519-528.

Abstract: The aim of this study was to compare the mechanical and intrinsic effects of an angiotensin converting enzyme inhibitor, vs a beta-blocker, on brachial arterial compliance. In a double blind study, 34 essential hypertensive patients were treated for 3 months with either ramipril 2.5-5.0 mg daily (n = 17, age 57 +/- 7 y, 11 males) or atenolol 50-100 mg daily (n = 17, age 53 +/- 8 y, 11 males). Blood pressure (BP), brachial artery diameter (D), brachial-radial pulse wave velocity (PWV) and effective compliance (Ceff), were measured before and at the end of the study. Isobaric evaluation (Ciso) was performed in the entire population studied at an average mean BP of 110 mmHg. Ramipril significantly reduced BP from 155 +/- 16/94 +/- 6 mmHg to 140 +/- 15/85 +/- 7 mmHg (p < 0.001) without affecting heart rate (HR; 74 +/- 10 vs. 75 +/- 12 bpm). In addition, it significantly improved both PWV (18%; p < 0.001) and arterial compliance (45%; p < 0.001), from which 35% was related to a pressure independent effect (p < 0.01). Atenolol also induced a reduction in both BP (159 +/- 17/96 +/- 10 to 133 +/- 13/81 +/- 8 mmHg; p < 0.001) and HR (76 +/- 10 to 57 +/- 7 bpm; p < 0.001). In a similar way, PWV (11%; p < 0.05) and Ceff (30%; p < 0.05) were significantly improved without significant change in Ciso. This suggests that blood pressure reduction was responsible for compliance improvement. In conclusion, it is suggested that atenolol induces only hemodynamic changes, mediated mainly by BP reduction. In contrast, the improved brachial buffering function observed after ramipril involves not only hemodynamic changes, but also changes mediated by other mechanisms, such as modification of wall structures.

Abstract: Effects of antihypertensive treatment on large arteries may be influenced by the type of drug and concomitant risk factors such as blood cholesterol. To explore these possibilities we investigated the common carotid artery of 20 subjects with low cholesterol and 19 subjects with high cholesterol, all with essential hypertension, randomly allocated to 3 months of treatment with nitrendipine (20 mg/d) or trandolapril (2 mg/d). Carotid parameters were determined by recording instantaneous pressure (applanation tonometry) and diameter (echotracking device) and by modeling the pressure-diameter loop to obtain the Peterson modulus, stiffness index, measured and isobaric compliances, and wall viscosity. Effects of drugs on carotid parameters did not differ, except on systolic and diastolic diameters (p < 0.01), which increased insignificantly under nitrendipine but decreased (p < 0.01) under trandolapril. Blood cholesterol status did not influence carotid effects of trandolapril, whereas patients with low and high cholesterol treated with nitrendipine exhibited significant differences in drug effects on (a) systolic and pulse pressures (p < 0.05), which decreased in patients with low cholesterol (p < 0.01, p < 0.05) but not in those with high cholesterol; (b) diastolic diameter (p = 0.05), which increased insignificantly in patients with low cholesterol but was unchanged in those with high cholesterol; and (c) wall viscosity (p < 0.01), which decreased in patients with low cholesterol (p < 0.05) but increased insignificantly in those with high cholesterol. Also, wall viscosity change under nitrendipine was positively related to the baseline blood cholesterol ( r = 0.64, p < 0.01). Thus, nitrendipine and trandolapril show noteworthy differences in their effects on the carotid artery, in particular with respect to the status of blood cholesterol, but these differences should be confirmed by larger studies.

Abstract: OBJECTIVES: We sought to investigate wall shear rate (WSR) and brachial artery diameter (BAD) changes simultaneously and to determine whether any gender differences exist in arterial reactivity. BACKGROUND: Wall shear rate/stress and arterial reactivity are rarely assessed at the same time. Furthermore, flow-mediated vasoconstriction has received less attention than flow-mediated vasodilation in humans. METHODS: A new noninvasive evaluation of WSR in the brachial artery, using multigated, pulsed Doppler velocimeter and a double-transducer probe moved and fixed by a robotic system, was developed. RESULTS: The validity of the system was tested in vitro with calibrated tubes and showed a high correlation (r = 0.98, p < 0.001). In 10 men and 10 women of similar age, induction of low and high shear rates by forearm occlusion produced significant vasoconstriction and vasodilation, respectively. The time lag for maximal BAD changes was 3 min for vasoconstriction and 1 min for vasodilation. A greater half-time for vasodilation (96 +/- 6 for men and 86 +/- 12 s for women) than for shear rate (31 +/- 5 s for men and 34 +/- 4 s for women) was observed after discontinuation of occlusion. Relative BAD was correlated with WSR changes, showing a significantly higher slope in women than in men (p < 0.01). Moreover, a larger normalized arterial diameter per shear rate was observed for vasoconstriction (p < 0.01) and vasodilation (p < 0.01) in women than in men. CONCLUSIONS: Shear-mediated arterial vasodilation and vasoconstriction were more pronounced in women than in men, suggesting different gender-related sensitivity in the regulation of large-artery vascular tone.

Abstract: A new automated computerized system (IôTEC) that assesses concomitantly the instantaneous temporal arterial diameter and intimal media thickness (IMT) obtained from B-mode ultrasound (US) images was validated by sonomicrometry in sheep, by an echo-tracking system in humans, and by a Lucite phantom in vitro. Differences between methods for diameter measurements did not vary in any systematic way, with no significant differences in the lower frequency range. Ultrasonic measurements of the true phantom gap sizes showed high correlation (r2 = 0.98,p < 0.001) with no systematic errors. Carotid and femoral arteries in humans were strongly related between IôTEC and echo-tracking device (r2 = 0.94 carotid; R2 = 0.88 femoral, p < 0.001), with a Gaussian distribution of the errors. This new method showed high intra- and interobserver repeatability of arterial diameter and IMT, allowing consistent characterization of arterial dynamics in humans.

Abstract: OBJECTIVE: The aim of this study is to evaluate the relationship between carotid intima-media thickness (IMT) and arterial wall inertial behaviour. METHODS: The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. The common carotid artery of eleven normotensive subjects (NTA) and eleven mild-to-moderate essential hypertensive patients (HTA) were measured noninvasively using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure (P) and diameter (D) loops. A linear discrete time model was used to estimate the inertial index (K(M)) using a system modelling-identification approach. RESULTS: In NTA K(M) was 0.333+/-0.256 (mmHg x s2/mm) and IMT 0.643+/-0.061 (mm), whereas in HTA K(M) was 0.798+/-0.590 (P < 0.05) and IMT 0.760+/-0.034 (P < 0.025). When all data of K(M) versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r = 0.61 (P < 0.05) was obtained. CONCLUSION: Wall inertia increase was associated with a higher IMT, suggesting that the intima-media thickening might be partially related to vascular hypertrophy manifested as increase of inertial behaviour.

Abstract: Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (eta) using the hysteresis loop elimination criteria. In NTA, eta was 2.73+/-1.66 (mm Hg x s/mm) and IMT was 0.58+/-0.08 (mm), whereas in HTA, eta was 5.91+/-2.34 (P<.025) and IMT was 0.70+/-0.12 (P<.025), respectively. When all data of eta versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r=.71 (P<.05) was obtained. Partial correlation between eta and IMT holding constant pressure was r=.59 (P<.05). In conclusion, wall viscosity increase was associated with a higher IMT even maintaining blood pressure fixed, suggesting that the intima-media thickening might be related to smooth muscle alterations manifested as an increase in viscous behavior.

Abstract: The effects of high blood pressure on arterial vessels has become an important topic of research. These effects can be evaluated by analyzing three major components: systemic vascular resistance, arterial compliance and wave reflection. The increase in systemic vascular resistance and arterial stiffness produces modifications of left ventricular afterload and morphologic changes of pressure and flow waves. These effects can eventually cause structural changes of the left ventricle, an increase in oxygen consumption and a decrease in coronary perfusion. Until recently, invasive methods were the only means to evaluate arterial function. The aim of this review is to assess the usefulness of non invasive methods to determine the components of arterial impedance in order to evaluate the hemodynamic changes due to high blood pressure.

Abstract: The influence of the renin-angiotensin system (RAS) on the aortic wall mechanical properties under angiotensin I converting enzyme inhibition (enalaprilat, 0.3 mg/kg iv) or angiotensin II receptor (AT1) blockade (E-3174, 1 mg/kg iv) was examined in eight normotensive and eight renovascular hypertensive conscious dogs. Aortic diameter (D; sonomicrometry)-pressure (P; microtransducer) hysteresis loops during steady state and during rapid distal aortic occlusion allowed (after hysteresis elimination) calculation of the aortic wall viscosity index, the purely elastic P-D relationship, and derivation into compliance-pressure curves. At the early stage ofrenovascular hypertension when activation of RAS is more pronounced, aortic wall stiffness and wall viscosity were increased as compared with normotensive states. Blood pressure remained unchanged in normotensive animals and was reduced during hypertension after antihypertensive treatments. In hypertensive animals, enalaprilat and E-3174 decreased viscosity index and shifted the compliance-pressure curve upward with respect to pretreatment conditions. In normotensive dogs, whereas E-3174 did not change the compliance-pressure curve and viscosity index, enalaprilat increased compliance and reduced viscosity index. We concluded that in normotensive dogs converting enzyme inhibition modifies arterial viscoelastic parameters by angiotensin-independent mechanisms that contribute to the modulation of the buffering function of large arteries.

Abstract: Knowledge about the viscoelastic behaviour of the arterial wall has been proved to have physiological importance and clinical usage. Our purpose was to study the changes of the systemic arterial wall's elastic properties non-invasively, in patients with established essential and with borderline hypertension, and to evaluate its possible determinants. Three groups of normotensive, borderline and established essential hypertensive patients were evaluated. Arterial pulse wave velocity (PWV) was measured and arterial compliance (Cm) was derived in all patients. Pulse wave velocity was obtained from the pressure values of digitized carotid and radial arteries. Arterial compliance (Cm = dD/dP with P pressure and D diameter) was calculated using a formula derived from the Bramwell and Hill equation: Cm = (1,334 x D)/(2 rho x PWV2), where for D humeral diameter was used as measured by high resolution echograph, and rho is the blood density (rho = 1.06). Pulse wave velocity was significantly higher in established essential hypertensive patients with respect to normotensive patients (p < 0.05). Arterial compliance was significantly diminished in established and in borderline hypertensive patients with respect to normotensive patients (p < 0.05), which implies early alterations in hypertensive cardiovascular disease. Multiple regression analysis of the cofactors showed that age and diastolic pressure are independent determinants of Cm. Impairment of the arterial wall's intrinsic elastic properties was demonstrated in established essential hypertension, independent of age and diastolic pressure.

Abstract: We compared the properties of common carotid and femoral arteries of 16 normotensive and 14 hypertensive men. Arterial pressure and diameter were recorded noninvasively in each vessel by tonometric and echotracking devices. The x-y composition of pressure and diameter waves provided the diameter-pressure hysteresis loop. The elastic diameter-pressure curve and wall viscosity index were deduced after hysteresis elimination. The compliance-pressure and distensibility-pressure curves were derived from the diameter-pressure curve, allowing the calculation of effective compliance and distensibility at the prevailing pressure of each subject and isobaric compliance and distensibility at the same standard pressure in all subjects. Systolic, diastolic, mean, and pulse pressures and diameters in each vessel were higher in the hypertensive than the normotensive group, except carotid pulse diameter, which did not differ. The carotid diameter-pressure, compliance-pressure, and distensibility-pressure curves did not differ between groups. In the carotid artery hypertensive patients had isobaric compliance and distensibility values similar to those of normotensive subjects, despite lower effective compliance (P < .05) and distensibility (P < .01). The femoral diameter-pressure curve was higher (P < .05) and the femoral compliance-pressure and distensibility-pressure curves were lower (P < .01) in the hypertensive than the normotensive group. Hypertensive patients had effective and isobaric femoral compliance and distensibility values lower than to those of normotensive subjects (P < .001). In both arteries, viscosity index was higher in the hypertensive than the normotensive group (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract:

Abstract: To evaluate arterial physiopathology, complete arterial wall mechanical characterization is necessary. This study presents a model for determining the elastic response of elastin (sigma E, where sigma is stress), collagen (sigma C), and smooth muscle (sigma SM) fibers and viscous (sigma eta) and inertial (sigma M) aortic wall behaviors. Our work assumes that the total stress developed by the wall to resist stretching is governed by the elastic modulus of elastin fibers (EE), the elastic modulus of collagen (EC) affected by the fraction of collagen fibers (fC) recruited to support wall stress, and the elastic modulus of the maximally contracted vascular smooth muscle (ESM) affected by an activation function (fA). We constructed the constitutive equation of the aortic wall on the basis of three different hookean materials and two nonlinear functions, fA and fC: sigma = sigma E + sigma C + sigma SM + sigma eta + sigma M = EE. (epsilon - epsilon 0E) + EC.fC.epsilon + ESM.fA.epsilon + eta. [equation: see text] + M.[equation: see text] where epsilon is strain and epsilon 0E is strain at zero stress. Stress-strain relations in the control state and during activation of smooth muscle (phenylephrine, 5 micrograms.kg-1.min-1 IV) were obtained by transient occlusions of the descending aorta and the inferior vena cava in 15 conscious dogs by using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements. The fC was not linear with strain, and at the onset of significant collagen participation in the elastic response (break point of the stress-strain relation), 6.02 +/- 2.6% collagen fibers were recruited at 23% of stretching of the unstressed diameter. The fA exhibited a skewed unimodal curve with a maximum level of activation at 28.3 +/- 7.9% of stretching. The aortic wall dynamic behavior was modified by activation increasing viscous (eta) and inertial (M) moduli from the control to active state (viscous, 3.8 +/- 1.3 x 10(4) to 7.8 +/- 1.1 x 10(4) dyne.s.cm-2, P < .0005; inertial, 61 +/- 42 to 91 +/- 23 dyne.s2.cm-2, P < .05). Finally, the purely elastic stress-strain relation was assessed by subtracting the viscous and inertial behaviors.

Abstract: A description of the arterial wall elastic properties comprehends both collagen and elastin, clearly shown in a biphasic stress-strain relationship. From chronically instrumented conscious dogs, aortic pressure-diameter curves can be obtained in a single beat, which is impossible to perform in human beings. In control conditions, the collagen fibers are almost not distended and the resistance to stretch is mainly supported by the elastin fibers. Therefore, the mechanical properties of the aorta are almost purely elastic in the basal beat to beat conditions. In this study we propose and test five indexes, which include as variables: systolic, diastolic and mean arterial pressure and diameter; besides, arterial compliance and pressure-strain elastic modulus as suggested to evaluate the elastic behaviour of the elastic fibers. This data can be easily obtained by non-invasive methods, such as Doppler-ultrasound techniques and auscultative esphygmomanometrical measurements, while the indexes evaluated can be retrieved from a single beat evaluation. Of three measurements performed in chronically instrumented conscious dogs on different days, one of these indexes, the ME5 = [formula: see text] x Rdias proved to be an accurate and reliable parameter to evaluate the mechanical behaviour of arteries. This kind of parameter may be useful for research and evaluation of several diseases that markedly alter the arterial wall compliance.

Abstract: Early investigators found contradictory evidence that vascular smooth muscle activation reduces the elastic modulus of the arterial wall under isotonic conditions but increases it under isometric conditions, concomitant with increased pulse-wave velocity. We examined the individual contributions of aortic constituents to the elastic modulus of the aortic wall to determine if isobaric analysis produces an accurate assessment of vascular smooth muscle activation. We used a modified Maxwell model assuming an incremental elastic modulus (Einc) composed of the elastic modulus of elastin fibers (EE), the elastic modulus of collagen fibers (EC) affected by the fraction of collagen fibers (fC) recruited to support wall stress, and the elastic modulus of the vascular smooth muscle (ESM) according to the following formula: Einc = EE+EC x fC+ESM.Einc was assessed in eight conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements. Stress-strain relations in the control state and during activation of smooth muscle by continuous administration of phenylephrine (5 micrograms.kg-1 x min-1) were obtained by transient occlusions of the descending aorta and inferior vena cava. Results were as follows: EE was 4.99 +/- 1.58 x 10(6) dynes/cm2 (mean +/- SD), and EC was 965.8 +/- 399.8 x 10(6) dynes/cm2, assessed during the control state. Phenylephrine administration increased the theoretical pulse-wave velocity (Moens-Korteweg equation) from 5.25 +/- 1.03 m/s during the control state to 7.57 +/- 2.53 m/s (P < .005). Active muscle exhibited a unimodal stress-strain curve with a maximum stress of 0.949 +/- 0.57 x 10(6) dynes/cm2 at a corresponding strain value of 1.299 +/- 0.083. The maximum value observed corresponded, on the pressure-diameter curve of the active artery, to a pressure of 234.28 +/- 46.6 mm Hg and a diameter of 17.94 +/- 1.6 mm. The maximum ESM derived from the stress-strain relation of the active muscle was 8.345 +/- 7.56 x 10(6) dynes/cm2 at a strain value of 1.283 +/- 0.079. This point was located at 208.01 +/- 40.8 mm Hg and 17.73 +/- 1.41 mm on the active pressure-diameter curve. During activation of vascular smooth muscle, Einc decreased (P < .05) when plotted against internal pressure but increased (P < .05) when plotted against strain, over the operative range.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract: OBJECTIVE: The aim was to assess the influence of the renin-angiotensin system on the geometrical and elastic properties of the aorta in conscious dogs, using a model of renovascular hypertension, and to examine the effects of inhibition of the system by the angiotensin converting enzyme inhibitor spirapril. METHODS: The aortic elastic behaviour in response to renovascular hypertension was studied in 15 conscious dogs instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. Renovascular hypertension was induced by surgical occlusion of one renal artery and stenosis of the other. One day after renal surgery, dogs were randomly assigned to two groups receiving for two months either the new angiotensin converting enzyme inhibitor spirapril (n = 8) or a placebo capsule (n = 7). The two groups of dogs were compared to a control group of normotensive dogs (n = 7). After two months of treatment the elastic properties of the aorta were studied by computation of the beat to beat pressure-diameter hysteresis loops obtained during transient increase of pressure induced by bolus doses of angiotensin. The aortic pressure-diameter (P-D) relationship, obtained over a wide range, was fitted by an exponential fit (P = alpha.e beta D), where beta is the stiffness index. A decomposition of the P-D curve according to a biphasic model of the parallel arrangement of elastin and collagen enabled two pressure-diameter elastic moduli to be obtained, one representing the resistance to stretch at low pressure levels (elastic fibres and smooth muscle), and the other representing the resistance to stretch at the highest pressures (collagen fibres). RESULTS: The pressure-diameter curve of the placebo group was shifted to the left compared to the curves of the control and spirapril groups, showing that renovascular hypertension was associated with isobaric reduction of aortic diameter. The stiffness index beta was higher (p < 0.05) in the placebo group [0.605(SD 0.304) mm-1] than in either the control group [0.362(0.126) mm-1] or the spirapril group [0.348(0.083) mm-1], suggesting that renovascular hypertension was associated with aortic stiffening. The biphasic analysis showed that the collagen pressure-diameter elastic modulus was unaffected by spirapril, whereas the elastin pressure-diameter elastic modulus was significantly reduced by converting enzyme inhibitor with respect to the placebo (p < 0.05). CONCLUSIONS: Chronic converting enzyme inhibition by spirapril prevents the isobaric aortic diameter reduction induced by renovascular hypertension in conscious dogs and decreases aortic stiffness, in particular by changing the elastic behaviour of the elastin fibres rather than of the collagen fibres.

Abstract: We studied the aortic elastic behavior in response to vitamin D3-induced accelerated calcinosis in conscious dogs chronically instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. The two functional phases of the elastic segmental properties of the aorta in vivo were discriminated by computation on a beat-by-beat basis from the phasic pressure-diameter (P-D) hysteresis loops in basal conditions and during the transient state of a wide range of pressures obtained mechanically (aortic occlusion) or pharmacologically (angiotensin bolus). The overall P-D curve formed by all P-D hysteresis loops was comprised of two linear relations according to a model that assumes that only elastin is stretched at lower pressures, whereas both elastin and collagen are stretched at higher pressures. The slope of the first linear portion of the P-D curve was considered as the elastin P-D elastic modulus, and the slope of the curve obtained by subtraction between the P-D curve and the extrapolation of the elastin straight line was assumed to be the collagen P-D elastic modulus. After vitamin D3-induced calcinosis, the elastin elastic modulus was unaffected, whereas the collagen elastic modulus decreased significantly during occlusion maneuvers (58.6%, p less than 0.01) and during bolus injections of angiotensin (37.2%, p less than 0.05). The collagen elastic modulus correlated with the serum calcium concentration (r = -0.65, p less than 0.001) and with the aortic pulse pressure (r = 0.51, p less than 0.01), and this relation persisted at constant heart rate. Histopathologic analysis evidenced calcium-depositing elastic lamina, focal disappearance of collagen, and rupture of elastic fibers. The present study shows that accelerated, severe, experimental calcinosis-inducing calcium deposition inside the large artery walls is accompanied by a clear-cut paradoxical reduction in arterial rigidity that is mainly due to functional and structural modification of collagen elasticity.

Abstract: The elastic behavior of total elastin (EE) and collagen (EC) and the recruitment of collagen fibers (FC) supporting wall stress at a given transmural pressure level were assessed in seven conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometer) measurements. Stress-strain relationships values calculated at control and during bolus administration of angiotensin and nitroglycerin enabled quantification of angiotensin and nitroglycerin enabled quantification of elastic moduli of elastin (EE = 4.868 +/- 1.753 x 10(6) dyn/cm2; means +/- SD) and collagen (EC = 1,306 +/- 637 x 10(6) dyn/cm2) according to a biphasic model of elastin and collagen parallel arrangement. The FC was found to be 6.1 +/- 2.6% at a pressure level of 118 +/- 16 mmHg. Values for EE and EC were similar to those reported in in vitro studies and showed scarce variability. This approach provides a quantitative evaluation of elastin and collagen moduli in conscious animals and also permits the evaluation of FC, which may be of interest in studies of connective tissue diseases involving the aortic wall.

Abstract: Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall.

Abstract: Laser beam constitutes a potential therapy in modern cardiology. Although its myocardial effects are known, they have been insufficiently evaluated at the surviving myocytes zone surrounding the evaporated crater. In order to assess myocyte cellular and organelar damage, we studied 8 isolated canine hearts radiated with different intensities by a CO2He laser beam 2.4, 3.5, 5, 15, 25, 30 and 40 Watts, varying the exposition time from 1 to 6 sec. Color photographs from the post-radiated lesions on front and depth were obtained. Their volumes were measured applying the cylinder and the cut out-conus formulas according to the shape of the lesions and then the involved tissues were embedded in paraffin for histological studies. Previously, samples of the lesions were fixed in glutaraldehyde for ultrastructural studies. Volumes of the craters were from 0.0004 to 19.57 mm3. Three layers were observed: a) a carbonized internal lining which measured x 15 microns in thickness; b) a coagulation necrotic zone ("gruyere cheese-like"), 70 microns thickness; c) finally more peripherally, a layer consisting of myocytes with patchy homogeneous cytoplasm, and scare positivity for the Barbeito López Trichome Stain (a positive technique in cases of myocardial damage). Ultrastructurally, crater peripherical cells showed cytosol and mitochondrial edema without membrane disruptions. These findings suggest that myocytes surrounding the laser beam crater, show reversible lesions. Therefore laser beam apperrs a safe procedure to be used in myocardium.

Abstract: To determine the effects of parasympathetic blockade and beta-blockade on the elastic response of aortic stiffness to vasopressive interventions, we studied 5 unanesthetised adult mongrel dogs by means of a pressure microtransducer and two ultrasonic crystals positioned at opposing sites in the proximal descending thoracic aorta which were used for diameter measurements. Systolic and diastolic changes in pressure and diameter were used to calculate Peterson and incremental elastic moduli. Acute hypertension was induced using infusions of epinephrine during the control period and later propranolol (1.5 mg/kg) plus atropine (0.2 mg/kg). Percent variations of mean aortic diameter were correlated to percent variations in mean aortic pressure in the control period and after autonomic blockade (P less than .001). The slopes of these correlations in the control group were higher than after autonomic blockade (P less than .05). Correlations were also found between Peterson and incremental elastic moduli and mean pressure in the control group and after autonomic blockade (P less than .001). The slopes of the correlations of incremental elastic modulus and Peterson's modulus versus mean aortic pressure were lower in the control group than after blockade (P less than .001). We conclude that in conscious dogs, autonomic blockade with propranolol and atropine decreased the distension and increased the stiffness of the aortic wall in response to acute hypertension mediated by epinephrine.

Abstract: A telemetric method has been designed for continuous measurement of intra-arterial aortic blood pressure in the unrestrained dog. The system used a Konigsberg P7 transducer, a temperature-compensated voltage-controlled oscillator, an FM transmitter, and an FM tuner to convert the signal received into a voltage proportional to aortic blood pressure. The method was validated by comparison with a standard direct method (using cables for transmission). Over a wide range of blood pressure obtained by hypotensive and hypertensive drugs (in total about 2500 data points, ranging from 40 to 200 mmHg), the telemetric method gave almost the same result as the direct method. Absolute error (telemetric measure minus standard measure) was normally distributed, with a mean value of -0.44 mmHg, and a standard deviation of 3.37 mmHg. The telemetric method was designed for future studies on the chronobiology of blood pressure in normal condition, in stress conditions and under drugs.

Abstract: Effects of experimental calcinosis induced by daily overdose of 500.000 IU Vit D3 during 10 days were studied in 6 mongrel conscious dogs chronically instrumented with intra-aortic Konigsberg microtransducer and two ultrasonic piezo-electric crystals diametrically opposed in the adventitia of the descending thoracic aorta. Simultaneous recording of instantaneous aortic pressure and diameter waves in basal state and during transient acute hypertension induced by intravenous angiotensin bolus (0.1 microgram/kg) allowed to obtain the pressure (y) diameter (x) relationship of the aorta according to an exponential regression: P = expo (beta D + A), with a highly significant correlation coefficient in all animals (r greater than 0.99). (table; see text) Anatomopathological studies of aortas revealed abnormal calcium deposition, ruptures of elastic fibers and disorganization of collagen. Thus, a striking decrease in aortic rigidity is observed after calcinosis in relation with structural changes of elastic materials and responsible in part for a reduction in pulsatile pressure; moreover this unexpected phenomena might represent an initiative process of development of aortic aneurysms.

Abstract: The aortic elastic behavior has been studied in conscious dogs chronically instrumented with a pressure microtransducer and two ultrasonic crystals. Pressure and diameter measurements were analyzed in terms of their mean values and systolic-diastolic variations, enabling calculation of Peterson elastic modulus, and were displayed in the x-y form to obtain pressure diameter hysteresis loops. After recovery from surgery and under autonomic blockade, intravenous perfusions of angiotensin, norepinephrine, and epinephrine were made at incremental steps of doses until steady-state pressure-diameter changes were achieved. The slopes of the positive pressure-diameter correlations obtained at each dose of the same vasoactive substance were higher for angiotensin than norepinephrine (p less than 0.01) and epinephrine (p less than 0.001) and were higher for norepinephrine than epinephrine (p less than 0.05). Similarly, the slopes of the elastic modulus to mean pressure relation were significantly lower for angiotensin than for norepinephrine (p less than 0.05) and epinephrine (p less than 0.001) and were significantly lower for norepinephrine than epinephrine (p less than 0.001). Thus, at the same transmural pressure, the distension and stiffness of the aorta were lower and higher with epinephrine than with norepinephrine, respectively, and with norepinephrine than with angiotensin suggesting different potencies of these drugs in terms of smooth muscle activation in the aorta.

Abstract: The elasticity of the thoracic aorta was studied in nine dogs instrumented with a pressure microtransducer and two ultrasonic crystals diametrically fixed in the adventitia. Systolic and diastolic changes in pressure and diameter were used to calculate Peterson and incremental elastic moduli. Acute hypertension was induced by infusions of angiotensin performed 1) during the control period, 2) after propranolol (1.5 mg/kg), 3) after atropine (0.2 mg/kg), and 4) after propranolol plus atropine. Absolute and percent variations of mean diameter were correlated to pressure in the control period and after autonomic blockade (p less than 0.01). The slopes of these correlations were not different between propranolol and control groups, but were lower with atropine (p less than 0.01) and with atropine plus propranolol (p less than 0.001) than in the control period. Correlations were also found between Peterson and incremental elastic moduli and mean pressure in the control period and after blockade (p less than 0.001). No differences of slopes existed between propranolol and control groups, but the slope of the correlation relative to the incremental elastic modulus was higher with atropine than in the control period (p less than 0.05), and the slopes of the correlations relative to the Peterson and the incremental elastic moduli were respectively higher with atropine plus propranolol than in the control period (p less than 0.05, p less than 0.05). Thus, atropine decreased the distention and increased the stiffness of the aorta in response to acute angiotensin-mediated hypertension.

Abstract: The elastic response of the thoracic aorta to increasing steps of angiotensin was studied in chronic instrumented conscious dogs with and without parasympathetic blockade by atropine. A pressure microtransducer and two ultrasonic crystals diametrically opposed and fixed in the adventitia enabled to determine the mean and systolic-diastolic changes of pressure (P) and diameter (D). By computing these measurements two representative indexes of dynamic elastic modulus in vivo were calculated; the elastic modulus of Peterson (Ep) Ep = delta P/D.D and the incremental elastic modulus (Ei) Ei = 0.75 EP/gamma, gamma being the ratio of the thickness to the external radius. A positive correlation (p less than 0.01) was obtained between pressure and diameter variations in the presence or absence of atropine but the slope of these relationship were lower with atropine than in controls. The slope of the positive correlations observed between Peterson and incremental elastic modulus and the increase in mean arterial pressure in response to angiotensin (p less than 0.01) was higher in the presence of atropine (p less than 0.05). These observations indicate that in response to angiotensin mediated high blood pressure, the cholinergic blockade of muscarinic receptors with atropine induce a contraction and increasing rigidity of the aorta.

Abstract: The viscoelastic behaviour of the aorta has been studied in 7 adult non-anesthesized mongrel dogs, chronically instrumented with a microtransducer pressure (Konigsberg P7) implanted inside the aortic lumen, and 2 ultrasonic crystals diametrically opposed and fixed in the adventitia of the thoracic aorta. Pressure and diameter were analysed in terms of mean values and of systolic diastolic variations, enabling to calculate the elastic modulus of Peterson. After recovery from surgery, and under autonomic blockade by atropine and propranolol, perfusions of angiotensin and norepinephrine were performed at incremental steps of doses. In individual dogs, instantaneous pressure-diameter relationships were formed by the different pressure diameter hysteris loops obtained at each dose of the same drug; the relationships obtained with the two drugs were curvilinear and were mixed at lower pressure ranges, but at highest levels of pressures it was found, that comparatively to angiotensin curve, that of norepinephrine had shifted toward lower diameter. The percent increase in mean diameter from baseline obtained at each dose of the same drug, was positively correlated to the corresponding per cent increase in mean pressure, with angiotensin (r = 0.83 P less than 0.001), and for norepinephrine (r = 0.82 P less than 0.001), but the slope of the relation was lower with angiotensin (22.3 +/- 3.2) than with norepinephrine (12.8 +/- 1.9) (P less than 0.001); likewise, the elastic modulus, for each dose of a same drug, was positively correlated to the corresponding mean pressure for angiotensin (r = 0.53 P less than 0.01), norepinephrine (r = 0.69 P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: We tested the ability of the slope (Emax) and the volume intercept (Vo) of the end-systolic pressure-volume relationship (ESPVR) to indicate contractility changes in conscious dogs instrumented with sonomicrometers measuring left ventricular diameter in three orthogonal axes and a left ventricular pressure microtransducer. ESPVRs were generated by inferior vena caval occlusion under control conditions (C1 and C2) and during enhanced (I+) and depressed (I-) inotropic states achieved by infusion of dobutamine and injection of propranolol, respectively. No significant difference between the first control (C1) and I+ or between the second control (C2) and I- were found for either Emax (C1, 5.31 +/- 1.68 mm Hg/ml, mean +/- SD; I+, 5.37 +/- 1.44; C2, 5.20 +/- 1.62; I-, 4.18 +/- 1.32) or Vo (C1, 10.3 +/- 9.6 ml; I+, 7.3 +/- 9.1; C2, 9.9 +/- 9.0; I-, 12.7 +/- 12.5), despite significant changes in other indexes of contractility. Comparison of changes in Emax in individual animals in response to I+ and I- revealed that 63% were nonsignificant, 28% were significant and expected, and 9% were significant and paradoxical. Within defined volume limits and irrespective of individual changes in Emax and Vo, in all animals I+ shifted the ESPVR above and to the left of C1 and I- shifted the ESPVR below and to the right of C2. We thus integrated the changes in Emax and Vo by measuring the area beneath each ESPVR between defined limits of end-systolic volume. The values for area were: C1, 612 +/- 150 mm Hg.ml; I+, 745 +/- 191 (p less than .001); C2, 520 +/- 198; I-, 420 +/- 139 (p less than .001). We conclude that (1) neither Emax nor Vo are individually reliable indexes of changed contractility, and (2) the area beneath the ESPVR between defined end-systolic volume limits is a consistent indicator of variations in inotropic state.

Abstract: Using three intraventricular diameter signals obtained from ultrasonic distance gauges and applying the general ellipsoid model to the left ventricle, it was possible to obtain the left ventricular volume signal. Implanting a miniature transducer in the left ventricle the pressure signal was attained. With these two signals the pressure-volume diagrams were constructed on line, and ventricular function during load manoeuvres could be studied from them. Because the whole process was done on line, using a microcomputer, the performance of the left ventricle to load manoeuvres in different conditions could be seen instantly.

Abstract: In order to correlate the percent of coronary lumen reduction measured by cineangiography and by pathology, we reviewed the coronary trees of 12 patients who died of coronary heart disease. The 36 arterial segments were divided in two groups: group I showing a good correlation in its 24 segments (less than 15% difference between both methods, r = 0.90), and group II (12 segments) with a poor correlation. No significant differences were found every time there was a greater than 70% stenosis. Milder lesions have a higher rate of discrepancies, due to pathology overestimation because of collapse of the vessel and tissue shrinkage, and to the angiographic underestimation that appears when comparing the stenotic segment with a remaining presumably normal artery.

Abstract: We describe a technique for the production of acute progressive right ventricular failure in experimental animals that mimics the hemodynamic characteristics of right ventricular failure found in some patients being weaned from extracorporeal circulation after surgical repair of left ventricular abnormalities. The technique combines three alterations of right ventricular state: excision of the tricuspid valve, ventriculotomy, and ligation of the right coronary artery. Seven control dogs died within 3 hours after this intervention. Death was due to low cardiac output as a result of low left atrial and pulmonary arterial pressures. Right atrial pressure was high. Use of a right ventricular assist device in an additional seven dogs to pump blood from the right atrium to the pulmonary artery confirmed good preservation of left ventricular function by reestablishing adequate left ventricular filling pressure. All seven dogs survived for more than 3 hours. The validity of the technique in restricting failure principally to the right ventricle was thus demonstrated.

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