Abstract: Uremic patients are prone to heart damage as a consequence of arteriovenous fistula (AVF) presence and hemodialysis treatment. Arteriovenous fistula induces hand ischemic syndrome and cardiac work increase, thus determining cardiac insufficiency in the medium to long term. This work investigates the cardiovascular mechanics evolution induced by the fistula presence. Twenty patients were enrolled; blood pressure, heart rate (HR), cardiac dimensions, and fistula flow were measured at scheduled intervals. A mathematical model of the cardiocirculatory system was implemented to simulate cardiovascular evolution. Input parameters were heart and vessel features; output of the model were cardiac performances indicators, partly reproducing measurable data and partly quantifiable only by using the model. Input and output variability and their long-term variations were analyzed. Blood pressure and peripheral resistance were found to be higher in uremic than in healthy subjects. Fistula tailoring showed increased cardiac fiber contractility and decreased peripheral resistances. Moreover, between 10 days and 3 months, an increased blood flow at the vascular access determined an increment in fiber contractility. In the same period, the 85% of the patients showed an increase in cardiac fiber stiffness. Similar but less pronounced trends were observed between 3 months and 1 year. The developed model reproduces the cardiovascular system in physiologic and pathologic conditions and allows description of the cardiovascular evolution for a uremic patient.
Abstract: Many experimental studies concerning nitric oxide (NO) release from endothelium and its vasodilative action are available in the literature, but no analytical description or modeling of these phenomena can be found. On the contrary, a large modeling literature is available concerning the other cardiovascular control mechanisms, such as the myogenic and metabolic control. In order to analytically describe these phenomena, a model of the endothelial control (defined in the Laplace domain and based on experimental data) was implemented and integrated with a lumped-parameter model of the systemic circulation, consisting of large artery segments and peripheral networks. The endothelial regulation model was based on the hypothesis proposed by Kuchan and Frangos, considering that NO release from the endothelium is generated by two parallel paths. The whole model was then applied to study the different vascular constriction or dilation under continuous or pulsatile perfusion, in order to better understand the clinical evidences of a poor organ perfusion in the presence of continuous with respect to pulsatile cardiopulmonary bypass. According to the experimental evidences, the main results obtained from the model revealed a widespread vascular constriction under continuous perfusion with respect to pulsatile. This result remains constant in the presence of different conditions of blood parameters and flow waveform.
Abstract: During the 6th International Symposium on Perfluorocarbon Application and Liquid Ventilation, a round table discussion on bioengineering was held in which different experts shared their opinions and experiences about the use of a total liquid ventilator design for clinical applications. To structure the discussion, all experts were invited to contribute their knowledge within the context of three matrixes related to the liquid ventilators: 1) function and technology, 2) ventilation modes, and 3) risk analyses. The outcome of this international conference recommends continued development of a total liquid ventilator toward clinical applications.
Abstract: ABSTRACT: BACKGROUND: This simulation study investigated potential modulations of total peripheral resistance (TPR), due to distributed peripheral vascular activity, by means of a lumped model of the arterial tree and a non linear model of microcirculation, inclusive of local controls of blood flow and tissue-capillary fluid exchange. RESULTS: Numerical simulations of circulation were carried out to compute TPR under different conditions of blood flow pulsatility, and to extract the pressure-flow characteristics of the cardiovascular system. Simulations showed that TPR seen by the large arteries was increased in absence of pulsatility, while it decreased with an augmented harmonic content. This is a typically non linear effect due to the contribution of active, non linear autoregulation of the peripheral microvascular beds, which also generated a nonlinear relationship between arterial blood pressure and cardiac output. CONCLUSION: This simulation study, though focused on a simple effect attaining TPR modulation due to pulsatility, suggests that non-linear autoregulation mechanisms cannot be overlooked while studying the integrated behavior of the global cardiovascular system, including the arterial tree and the peripheral vascular bed.
Abstract: Negative pressure generated during the expiratory phase of total liquid ventilation (TLV) may induce airway collapse. Evaluation of the effect of repeated airway collapse is crucial to optimize this technique. A total of 24 New Zealand White rabbits were randomly divided into four groups. Ventilation was performed for 6 hours with different strategies: conventional gas ventilation, TLV without airway collapse, and TLV with collapse induced in either 75 or 150 sequential breaths. In the treated groups, airway collapse was induced by increasing the perfluorocarbon drainage velocity while maintaining the minute ventilation constant. Airway pressure, gas exchange, and blood pressure were monitored at 30-minute intervals. At the end of the experiment, airway and lung parenchyma specimens were processed for light microscopy. No evidence of fluorothorax was noticed in any of the four groups at autopsy examination. Minimal signs of inflammation were noticed in all airway and lung parenchyma specimens, but no evident structural alteration was visible. Adequate gas exchange and systemic blood pressure were maintained during all the studies. Repeated airway collapse is not associated with structural changes in the respiratory system and does not alter the gas exchange ability of the lungs.
Abstract: BACKGROUND: Several factors are involved in the pathogenesis of dialysis discomfort interfering with optimal fluid removal and reducing the efficacy of the treatment; the most important one is a decrease in blood volume caused by an imbalance between ultrafiltration (UF) and plasmarefilling (PR) rates. OBJECTIVES: This study is aimed at devising a method to tailor the dialysis therapy to each individual patient, by analyzing the relationship between PR and UF during the sessions in stable patients and widening the knowledge of fluid exchanges during the treatment. METHODS: Thirty stable patients undergoing maintenance hemodialysis were enrolled. Three dialysis sessions were monitored for each patient; systemic pressure, blood composition, blood volume % variation, weight loss and conductivity were recorded repeatedly. A Plasma Refilling Index (PRI), defined and calculated by means of parameters measured throughout the dialysis, was introduced as a novel instrument to study plasma refilling phenomena. Results. The PRI provides understanding of patient response (in terms of plasma refilling) to the set UF. In the monitored sessions, the PRI trend is found to be characteristic of each patient; a PRI course that is at variance with the characteristic trend is a signal of inadequate or unusual dialysis scheduling. Moreover, statistical analysis highlights two different PRI trends during the first hour and during the rest of the treatment, suggesting the presence of different treatment phases. CONCLUSION: The main advantage of the PRI index is that it is non-invasive peculiar to each patient and easy to compute in a dialysis routine based on online data recorded by the monitor. A deviation from the characteristic trend may be a warning for the clinician. The analysis of the PRI trend also suggests how to modulate UF as a function of interstitial to intravascular fluid removal balance during dialysis.
Abstract: To quantify cardiac apex rotation (CAR), the authors recently proposed the use of a Coriolis force sensor (gyroscope) as an alternative to other complex techniques. The aim of this study was to evaluate the effects of right ventricular (RV) pacing on CAR. A sheep heart was initially paced from the right atrium to induce a normal activation sequence at a fixed heart rate (AAI mode) and then an atrioventricular pacing was performed (DOO mode, AV delay = 60 ms). A small gyroscope was epicardially glued on the cardiac apex to measure the angular velocity (Ang V). From AAI to DOO pacing mode, an increase (+9.2%, p < 0.05) of the maximum systolic twisting velocity (Ang VMAX) and a marked decrease (-19.9%, p < 0.05) of the maximum diastolic untwisting velocity (Ang VMIN) resulted. RV pacing had negligible effects (-3.1%, p = 0.09) on the maximum angle of CAR, obtained by integrating Ang V. The hemodynamic parameters of systolic (LVdP/dtMAX) and diastolic (LVdP/dtMIN) cardiac function showed slight variations (-3.8%, p < 0.05 and +3.9%, p < 0.05, respectively). Results suggest that cardiac dyssynchrony induced by RV pacing can alter the normal physiological ventricular twist patterns, particularly affecting diastolic untwisting velocity.
Abstract: Peripheral vasomotion, interstitial liquid exchange, and cardiovascular system behaviour are investigated by means of a lumped parameter model of the systemic and peripheral circulation, from the aortic valve to the venules. This modelling work aims at combining arterial tree hemodynamics description, active peripheral flow regulation, and fluid exchange. The arterial compartment is constructed with 63 RCL segments and 30 peripheral districts including myogenic control on arterioles, metabolic control on venules, and Starling filtration through capillary membrane. The arterial behaviour is characterised as to the long term stability of pressure/flow waves in the different segments. Peripheral districts show autoregulatory capabilities against pressure changes over a wide range and also self-sustained oscillations mimicking vasomotor activity. A preliminary study was carried out as to the model response to changes induced by cardiopulmonary bypass (CPB). Among the induced alterations, the system responds mainly to hemodilution, which increased peripheral fluid loss and oedema beyond the compensatory capabilities of local regulation mechanisms. This resulted in an overall increase total arterial resistance. Local transport deficits were assessed for each district according to the different metabolic demand. This study shows the requirement of a suitable description of both arteries and peripheral mechanisms in order to describe cardiovascular response non-physiological conditions, as well as assisted circulation or other pathological conditions.
Abstract: This study analyzes the structure and mechanical properties of the trachea of the striped dolphin Stenella coeruleoalba, one of the most common cetacean species. The cetacean trachea is made up of closed or semiclosed cartilaginous rings without a paries membranaceus. Our results indicate that the inner lining of the trachea contains erectile tissue in which several venous lacunae permeate the mucosa. We also observed and described the presence of peripheral neurons containing nitric oxide along the rim of the venous lacunae. Data obtained from compression and tensile tests and comparison with the pig and goat tracheas indicate a higher stiffness and a different, higher breaking point for the dolphin trachea. On the whole, our data suggest that the trachea of the striped dolphin possesses structural properties that allow rapid filling with blood, possibly in relation to dive activities, and also allow modifications due to increased pressure and immediate return to the original shape without risks of permanent bending or rupture, as would happen in a terrestrial mammal. As the organ undergoes intense pressure difference during descent to optimal foraging depth and subsequent rapid ascent to surface, especially in deep dives of hundreds of meters, the specific structural and biomechanical peculiarities of the trachea of the striped dolphin may represent an evolutionary adaptation to life in the water and to diving.
Abstract: A new model lung (ML), designed to reproduce the tracheal pressure vs. fluid flow relationship in animals undergoing total liquid ventilation (TLV) trials, was developed to be used as a mock bench test for neonatal TLV circuits. The ML is based on a linear inertance-resistance-compliance (LRC) lumped-parameter model of the respiratory system with different resistance values for inspiration (R insp ) or expiration (R exp ). The resistant element was set up using polypropylene hollow fibres packed inside a tube. A passive one-way valve was used to control the resistance cross-section area provided for the liquid to generate different values for R insp or R exp , each adjustable by regulating the active length of the respective fibre pack. The compliant element consists of a cylindrical column reservoir, in which bars of different diameter were inserted to adjust compliance (C). The inertial phenomena occurring in the central airways during TLV were reproduced by specifically dimensioned conduits into which the endotracheal tube connecting the TLV circuit to the ML was inserted. A number of elements with different inertances (L) were used to simulate different sized airways. A linear pressure drop-to-flow rate relationship was obtained for flow rates up to 5 l/min. The measured C (0.8 to 1.3 mL cmH2O (-1) kg(-1)), R insp (90 to 850 cmH2O s l(-1)), and R exp (50 to 400 cmH2O s l(-1)) were in agreement with the literature concerning animals weighing from 1 to 12 kg. Moreover, features observed in data acquired during in vivo TLV sessions, such as pressure oscillations due to fluid inertia in the upper airways, were similarly obtained in vitro thanks to the inertial element in the ML.
Abstract: Knowledge of the mechanical behaviour of immature tracheae is crucial in order to understand the effects exerted on central airways by ventilatory treatments, particularly of Total Liquid Ventilation. In this study, a combined experimental and computational approach was adopted to investigate the compliance and particularly collapsibility of preterm lamb tracheae in the range of pressure likely applied during Total Liquid Ventilation (-30 to 30 cmH2O). Tracheal samples of preterm lambs (n = 5; gestational age 120-130 days) were tested by altering transmural pressure from -30 to 30 cmH2O. Inflation (Si) and collapsing (Sc) compliance values were calculated in the ranges 0 to 10 cmH2O and -10 to 0 cmH2O, respectively. During the tests, an asymmetric behaviour of the DeltaV/V0 vs. P curves at positive and negative pressure was observed, with mean Si = 0.013 cmH2O(-1) and Sc = 0.053 cmH2O(-1). A different deformed configuration of the sample regions was observed, depending on the posterior shape of cartilaginous ring. A three-dimensional finite-element structural model of a single tracheal ring, based on histology measurements of the tested samples was developed. The model was parameterised in order to represent rings belonging to three different tracheal regions (craniad, median, caudal) and numerical analyses replicating the collapse test conditions were performed to evaluate the ring collapsibility at pressures between 0 and -30 cmH2O. Simulation results were compared to experimental data to verify the model's reliability. The best model predictions occurred at pressures -30 to -10 cmH2O. In this range, a model composed of median rings best interpreted the experimental data, with a maximum error of 2.7%; a model composed of an equal combination of all rings yielded an error of 12.6%.
Abstract: Tidal liquid ventilation (TLV) was proposed as an alternative to conventional mechanical ventilation in the case of surfactant-deficiency diseases, particularly for very premature subjects. Although many experimental studies have been conducted up to now, the effects of variations in ventilatory settings, such as frequency and tidal volume, on blood arterialization and lung mechanics have not been studied quantitatively. We developed a mathematical model simulating the breathing processes occurring during neonatal TLV treatments. The model integrates the description of O2 and CO2 transport, from the trachea to pulmonary capillary blood and vice versa, with the description of fluid mechanics within the airways and the saccules (the alveoli precursors). Gas transfer is described with a mono-dimensional model, accounting for convective and diffusive transport through the airways, coupled with a 3-compartment model, simulating gas diffusion between saccules, plasma and red blood cells, and chemical reactions dependent on the concentrations of gases and related chemical species. Mechanic loads on airways are calculated by means of a lumped-parameters approach. The model calculates mechanical stress and gas exchange as a function of the ventilatory settings. The integration of these results sheds light on possible ventilation strategies to allow for optimal management of blood arterialization and lung mechanical load.
Abstract: The vacuum-assisted venous drainage (VAVD) technique has been introduced with the utilization of small-bore venous cannulae to facilitate minimally invasive cardiac surgery and it has found widespread use for traditional surgical approaches. Although this technique was devised to increase venous return, it may cause a reduction of blood flow through a negative pressure effect on the raceway tubing. In this study, the potential of this system to increase the venous drainage was evaluated in vitro together with the measurements of delivered blood flow. The VAVD has been tested in association with normal gravitational drainage or as a substitute for gravitational drainage. The flow was calculated by multiplying the pump rate by the stroke volume and it was simultaneously measured by a magnetic flowmeter. A steady state maximal flow was defined as the flow that could maintain a constant level of fluid in the graduated canister used to act as the patient. Based on our results, the VAVD can increase venous drainage by as much as 50% above baseline levels. However, delivered blood flow may be overestimated, particularly when negative pressure values > 60 mmHg are employed. A 100 mmHg negative pressure may produce an overestimate of blood flow as great as 54% of the measured flow.
Abstract: The aim of this study was to investigate the effect of tidal liquid ventilation (TLV) compared to conventional mechanical ventilation (CMV) on oxidative lung damage in the setting of acute respiratory distress syndrome (ARDS). After repeated lung lavages, 10 minipigs were treated with CMV or TLV for 4 hr before the animals were sacrificed. Samples for blood gas analysis and bronchial aspirate samples were withdrawn before the induction of lung injury, and at 10 min, 2 hr, and 4 hr after the beginning of ventilatory support. To assess lung oxidative damage, total hydroperoxide (TH) and advanced oxidation protein product (AOPP) concentrations were measured in bronchial aspirate samples. After 2 and 4 hr of ventilatory support, partial oxygen tension (PaO(2)) and base excess (BE) were significantly higher in the TLV group than in the CMV group, while PaCO(2) was slightly higher, but with no statistical significance. In the CMV group, the AOPP level was significantly higher at 4 hr than at baseline. TH and AOPP bronchial aspirate concentrations were higher in the CMV group than in the TLV group at 2 and 4 hr of ventilation. We conclude that animals treated with TLV showed lower oxidative lung damage compared to animals treated with CMV.
Abstract: Conventional gas ventilation is often unsuccessful for premature neonatal patients suffering from respiratory distress syndrome (RDS). For such patients, liquid ventilation (LV) with perfluorocarbon (PFC) liquids has been proposed. By eliminating the air-liquid interface in saccules (the premature gas exchange structures), where scarce or absent surfactant production exists, pulmonary instability is avoided, lung compliance is improved, and atelectatic saccules are recruited, ultimately lowering the saccular pressure. Tidal LV involves administrating a liquid tidal volume to the patient at each respiratory cycle, and therefore requires a dedicated circuital setup to deliver, withdraw, and refresh the PFC during the treatment. We have developed a prototype liquid breathing system (LBS). The apparatus comprises two subcircuits managed by a personal computer based control system. The ventilation subcircuit performs inspiration/expiration with two sets of peristaltic pumps. A system to evaluate the true inspired/expired volumes was devised that consists of two reservoirs equipped with pressure transducers measuring the hydraulic head of the fluid therein. Volume accuracy was +/- 0.3 ml. The refresh subcircuit properly processes the PFC by performing filtration (DFA, Pall, NY), oxygenation, CO2 scavenge, and heat exchange (SciMed 2500, Life Systems, MN). The new apparatus has been used in preliminary animal tests on five newborn mini pigs with induced acquired RDS. The PFC used was RM-101 (Miteni, Milano, Italy). The animals were successfully supported for 4 hours each. Mean arterial O2 pressure was 131.4 mm Hg (range 79.0-184.2), and mean arterial CO2 pressure was 64.8 mm Hg (range 60.0-73.4).
Abstract: The partitioning of umbilical vein blood flow between fetal liver and ductus venosus may be an indicator of the fetal well-being, because the goal of the ductus venosus is to supply oxygen and nutrients to heart and brain. Both distribution and blood flow rate of the umbilical vein are functions of the local vascular impedances that, in turn, depend on the anatomical features of the related vessels. In order to investigate the venous blood flows in human fetuses during a normal gestation, a simple lumped parameter mathematical model was developed on the basis of some information achievable by ultrasonographic techniques. Particularly, the diameter and length of umbilical vein and ductus venosus and the volume of the liver were used to derive the vascular impedances. Three different impedance models were adopted for the umbilical vein, the ductus venosus and the hepatic circulation. A linear model described viscous hydraulic dissipations through the umbilical vein, while a quadratic pressure-flow relationship was used for the ductus venosus due to the irregular local hemodynamics at its inlet. Finally, the equivalent impedance of the whole hepatic network was related to the hepatic volume assuming a tree-like, symmetric and self-similar fractal geometry. The hepatic vascular resistances predicted according to the fractal analysis were quite consistent with some experimental measurements in fetal lambs. In agreement with clinical observations, the model predicted blood flows through the ductus venosus and umbilical vein increasing (from about 25 to 75 ml/min and from about 45 to 370 ml/min, respectively) throughout the gestation (20-40 weeks), while the flow fraction shunted via the ductus venosus diminishes (from about 50 to 20%).
Abstract: In order to move towards extracorporeal circulation (ECC) automation, a virtual simulation of the process was designed. The ECC model is composed of a virtual patient linked to a virtual ECC circuit. A user interface panel allows to set control parameters for the simulation and to visualize results. It is possible to switch between manual and automatic control. Meaningful hemodynamic and hematochemical variables are continuously shown along with a score (from 0 to 10). The virtual model can play a crucial role in educating and training the personnel devoted to the managing of the heart-lung machine.
Abstract: Tidal liquid ventilation (TLV) with perfluorocarbons (PFC) has been proposed to treat surfactant-deficient lungs of preterm neonates, since it may prevent pulmonary instability by abating saccular surface tension. With a previous model describing gas exchange, we showed that ventilator settings are crucial for CO(2) scavenging during neonatal TLV. The present work is focused on some mechanical aspects of neonatal TLV that were hardly studied, i.e. the distribution of mechanical loads in the lungs, which is expected to differ substantially from gas ventilation. A new computational model is presented, describing pulmonary PFC hydrodynamics, where viscous losses, kinetic energy changes and lung compliance are accounted for. The model was implemented in a software package (LVMech) aimed at calculating pressures (and approximately estimate shear stresses) within the bronchial tree at different ventilator regimes. Simulations were run taking the previous model's outcomes into account. Results show that the pressure decrease due to high saccular compliance may compensate for the increased pressure drops due to PFC viscosity, and keep airway pressure low. Saccules are exposed to pressures remarkably different from those at the airway opening; during expiration negative pressures, which may cause airway collapse, are moderate and appear in the upper airways only. Delivering the fluid with a slightly smoothed square flow wave is convenient with respect to a sine wave. The use of LVMech allows to familiarize with LV treatment management taking the lungs' mechanical load into account, consistently with a proper respiratory support.
Abstract: A new project is presented, the pumping oxygenator, functionally integrating pulsatile pumping and blood oxygenation in a single device. Solid, semipermeable silicone membranes allow gas exchange and simultaneously transfer energy from pressurized gas to blood thanks to their distensibility and to inlet and outlet 1-way valves. Two small-sized (1 m2 exchange surface area) prototypes were designed, constructed, hydraulically characterized, and subjected to gas transfer evaluation tests. Blood flow rates (Q(b)) up to 1,250 ml/min were obtained with 30 mm Hg static preload and 130 mm Hg afterload with 0.7 m upstream and 2.1 m downstream 3/8 inch pipes. Physiological oxygen transfer (VO2 = 5 ml/dl, ml of transferred O2/dl of treated blood) was delivered at Q(b) < 900 ml/min, about 4 ml/dl at Q(b) = 1,250 ml/min. VO2 also was significantly increased by increasing percent systolic time. CO2 transfer decreased regularly with increasing Q(b) from VCO2 = 4.8 ml/dl at Q(b) = 400 ml/min to VCO 2 = 2.1 ml/dl at Q(b) = 1,250 ml/min. The results confirm the possibility of integrating oxygenation and pulsatile pumping. The pumping oxygenator represents a promising project deserving further improvements.
Abstract: Fifteen elderly patients, 13 of them undergoing chronic haemodialysis, 1 acute and 1 coming from Continuous Ambulatory Peritoneal Dialysis (CAPD) either with no significant cardiovascular alteration or presenting various cardiovascular pathologies were studied to investigate the possibility of onset of hypotensive episodes during dialytic treatment depending on cardiac or vascular alteration in the patients. Monitoring of the arterial pressure on the contralateral arm and on the lower limbs by using the Takeda System, made it possible to compute the Windsor Index (WI). The figures obtained were correlated to the Ejection Fraction Index (EFI) to investigate the relation between WI alteration and haemodynamic variations in the patient. The results show that cardiothoracic recirculation is much more present in those patients with pathologies that affect EFI which worsens during dialysis due to the loss of fluid. Moreover the results obtained from the two patients with temporary access and no evident cardiovascular pathology show the constancy of the haemodynamic parameters throughout the dialytic treatment.
