Abstract: Iron is tightly connected to oxygen homeostasis and erythropoiesis. Our aim was to better understand how hypoxia regulates iron acquisition for erythropoiesis in humans, a topic relevant to common hypoxia-related disorders. Forty-seven healthy volunteers participated in the HIGHCARE project. Blood samples were collected at sea level and after acute and chronic exposure to high altitude (3400-5400 m above sea level). We investigated the modifications in hematocrit, serum iron indices, erythropoietin, markers of erythropoietic activity, interleukin-6, and serum hepcidin. Hepcidin decreased within 40 hours after acute hypoxia exposure (P < .05) at 3400 m, reaching the lowest level at 5400 m (80% reduction). Erythropoietin significantly increased (P < .001) within 16 hours after hypoxia exposure followed by a marked erythropoietic response supported by the increased iron supply. Growth differentiation factor-15 progressively increased during the study period. Serum ferritin showed a very rapid decrease, suggesting the existence of hypoxia-dependent mechanism(s) regulating storage iron mobilization. The strong correlation between serum ferritin and hepcidin at each point during the study indicates that iron itself or the kinetics of iron use in response to hypoxia may signal hepcidin down-regulation. The combined and significant changes in other variables probably contribute to the suppression of hepcidin in this setting.
Abstract: high-altitude adaptation leads to progressive increase in arterial Pa(O2). In addition to increased ventilation, better arterial oxygenation may reflect improvements in lung gas exchange. Previous investigations reveal alterations at the alveolar-capillary barrier indicative of decreased resistance to gas exchange with prolonged hypoxia adaptation, but how quickly this occurs is unknown. Carbon monoxide lung diffusing capacity and its major determinants, hemoglobin, alveolar volume, pulmonary capillary blood volume, and alveolar-capillary membrane diffusion, have never been examined with early high-altitude adaptation.
Abstract: Aims: Exposure to high altitude (HA) hypoxia decreases exercise performance in healthy subjects. Although β-blockers are known to affect exercise capacity in normoxia, no data are available comparing selective and nonselective β-adrenergic blockade on exercise performance in healthy subjects acutely exposed to HA hypoxia. We compared the impact of nebivolol and carvedilol on exercise capacity in healthy subjects acutely exposed to HA hypobaric hypoxia. Methods: In this double-blind, placebo-controlled trial, 27 healthy untrained sea-level (SL) residents (15 males, age 38.3 ± 12.8 years) were randomized to placebo (n = 9), carvedilol 25 mg b.i.d. (n = 9), or nebivolol 5 mg o.d. (n = 9). Primary endpoints were measures of exercise performance evaluated by cardiopulmonary exercise testing at sea level without treatment, and after at least 3 weeks of treatment, both at SL and shortly after arrival at HA (4559 m). Results: HA hypoxia significantly decreased resting and peak oxygen saturation, peak workload, VO(2) , and heart rate (HR) (P < 0.01). Changes from SL (no treatment) differed among treatments: (1) peak VO(2) was better preserved with nebivolol (-22.5%) than with carvedilol (-37.6%) (P < 0.01); (2) peak HR decreased with carvedilol (-43.9 ± 11.9 beats/min) more than with nebivolol (-24.8 ± 13.6 beats/min) (P < 0.05); (3) peak minute ventilation (VE) decreased with carvedilol (-9.3%) and increased with nebivolol (+15.2%) (P= 0.053). Only peak VE changes independently predicted changes in peak VO(2) at multivariate analysis (R= 0.62, P < 0.01). Conclusions: Exercise performance is better preserved with nebivolol than with carvedilol under acute exposure to HA hypoxia in healthy subjects.
Abstract: To investigate the effects of hypoxia during sleep on linear and self-similar components of heart rate variability (HRV) in eight healthy subjects at high altitude on Mount Everest.
Abstract: The management of high blood pressure (BP) is particularly inadequate in low-income countries, where the unavailability of a reliable, durable, and affordable BP-measurement device is a major obstacle to accurate diagnosis. Recognizing this, a World Health Organization committee was established to correct this deficiency by influencing manufacturers to produce a device according to predetermined criteria and to demonstrate the suitability of the device for low resource settings. A device, which fulfilled stipulated criteria in being inexpensive, semiautomated, and solar powered, was validated according to the International Protocol of the European Society of Hypertension; it was then subjected to field testing in 716 subjects from 2 centers in Uganda and 1 in Zambia. The Omron HEM-SOLAR having previously fulfilled accuracy criteria of the International Protocol for both systolic blood pressure (SBP) and diastolic blood pressure (DBP), fulfilled criteria for SBP, but not for DBP, when revalidated. In field testing, average SBPs and DBPs were 120.5 ± 21.6/74.6 ± 13.8 mm Hg and 122.3 ± 21.8/71.2 ± 14.0 mm Hg, respectively, with the auscultatory technique and the Omron HEM-SOLAR, respectively. Between-device agreement in defining SBP was 93.7%. The Omron HEM-SOLAR was favored over the mercury sphygmomanometer by both patients and investigators. In summary, considering the accuracy, robustness, relatively low cost, operational simplicity, and advantages such as solar power, the Omron HEM-SOLAR is likely to be a valuable device for improving BP measurement in low-resource settings with nonphysician health workers.
Abstract: It is unknown whether subclinical high-altitude pulmonary oedema reduces spontaneously after prolonged altitude exposure. Continuous positive airway pressure (CPAP) removes extravascular lung fluids and improves haemoglobin oxygen saturation in acute cardiogenic oedema. We evaluated the presence of pulmonary extravascular fluid increase by assessing CPAP effects on haemoglobin oxygen saturation under acute and prolonged altitude exposure.
Abstract: Immunophenotypic modulation is induced by steroids in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients during remission induction therapy.
Abstract: Seismocardiogram (SCG) is the recording of body vibrations induced by the heart beat. SCG contains information on cardiac mechanics, in particular heart sounds and cardiac output. In this paper we present a new wearable device for SCG recordings during long term monitorings, and the results of a validation test in 4 subjects. The system is based on the integration of the MagIC smart shirt (i.e., a textile-based wearable system for the assessment of ECG and respiratory movements), and an external triaxial MEMS accelerometer positioned on the left clavicle. SCG was estimated as the average of accelerations occurred in each heart beat. The SCG components due to the valve closure and to recoil forces following the heart contraction (ballistocardiogram) were extracted by high-pass (>18 Hz) and band-pass (0.6-20 Hz) filters respectively. Then the difference between the I and J waves of the ballistocardiogram (|I-J| index, possibly related to the cardiac output) was identified by an ad-hoc procedure and compared with the model flow indirect estimation of cardiac output. Validation on 4 volunteers showed that: 1) our wearable system provides statistically consistent estimates of both heart-sound related vibrations and recoil movements; 2) reliable estimates of the |I-J| index can be obtained by considering about 1 minute of SCG recording in stationary conditions; and 3) changes of the |I-J| index during exercise correlate well with changes of cardiac output estimated by the model flow.
Abstract: On the basis of indirect evidences it has been hypothesized that during space missions the almost complete absence of gravity might impair the baroreflex control of circulation. In the first part of this paper we report results obtained from a series of experiments carried out to directly verify this hypothesis during the 16-day STS 107 Shuttle flight. Spontaneous baroreflex sensitivity was assessed in four astronauts before flight (baseline) and at days 0-1, 6-7 and 12-13 during flight, both at rest and while performing moderate exercise. Our results indicate that at rest the baroreflex sensitivity significantly increased in the early flight phase, as compared to pre-flight values and tended to return to baseline in the mid-late phase of flight. During exercise, baroreflex sensitivity was lower than at rest, without any difference among pre-flight and in-flight values. These findings seem to exclude the hypothesis of an impairment of the baroreflex control of heart rate during exposure to microgravity, at least over a time window of 16 days. In the second part of the paper we propose a novel textile-based methodology for heart rate and other vital signs monitoring during gravity stress. The positive results obtained from its use during parachute jumps support the use of smart garments for the unobtrusive assessment of physiological parameters in extreme environments.
Abstract: Blood pressure (BP) fluctuations over time physiologically result from the complex interaction between environmental stimulation, genetic factors, and cardiovascular control mechanisms. Ambulatory BP-monitoring techniques, in particular systems providing beat-by-beat BP recording, have allowed a detailed description of the different components contributing to overall BP variability (BPV) over 24 hours, including short-lasting and more sustained BP changes. In hypertension, BPV increases with increasing BP levels, and evidence is available that its magnitude correlates closely with target-organ damage and with the incidence of cardiovascular events, independent of absolute BP levels. It has been suggested that drugs capable of providing smooth 24-hour BP control, reducing BPV, may confer additional target-organ protection. Mathematic indices, such as the trough-to-peak ratio and the smoothness index, represent useful measures of the homogeneity of the antihypertensive effect over 24 hours. Further studies are still needed to confirm that, in humans, interventions that can reduce BPV can also reduce the rate of cardiovascular events.
Abstract: Assessment of minimal residual disease (MRD) by flow cytometry is considered to be based on the reproducibility of the leukemic immunophenotype detected at diagnosis. However, we previously noticed modulation of surface antigen expression in acute lymphoblastic leukemia (ALL) during the early treatment. Hence, we investigated this in 30 children with B-cell precursor ALL consecutively enrolled in the AIEOP-BFM ALL 2000 protocol. Quantitative expression of seven antigens useful in MRD monitoring was studied at diagnosis and compared to that measured at different time points of remission induction therapy. Downmodulation in the expression of CD10 and CD34 occurred at follow-up. By contrast, upmodulation of CD19, CD20, CD45RA, and CD11a was observed, while the expression of CD58 remained stable. Despite this, we could unambiguously discriminate leukemic cells from normal residual B cells. This holds true when bone marrow (BM) samples from similarly treated T-ALL patients, but not from healthy donors, were used as reference. Our results indicate that immunophenotypic modulation occurs in ALL during the early phases of BFM-type protocols. However, the accuracy of MRD detection by flow cytometry seems not negatively affected if adequate analysis protocols are employed. Investigators should take this phenomenon into account in order to avoid pitfalls in flow cytometric MRD studies.
Abstract: Hemodialysis (HD) is associated with cardiovascular structural modifications; moreover, during HD, rapid electrolytic changes occur. Both factors may favor the onset of atrial fibrillation.
Abstract: We studied responses of endothelial and epithelial cells in the thin portion of the air-blood barrier to a rise in interstitial pressure caused by an increase in extravascular water (interstitial edema) obtained in anesthetized rabbits receiving saline infusion (0.5 ml.kg(-1).min(-1) for 3 h). We obtained morphometric analyses of the cells and of their microenvironment (electron microscopy); furthermore, we also studied in lung tissue extracts the biochemical alterations of proteins responsible for signal transduction (PKC, caveolin-1) and cell-cell adhesion (CD31) and of proteins involved in membrane-to-cytoskeleton linkage (alpha-tubulin and beta-tubulin). In endothelial cells, we observed a folding of the plasma membrane with an increase in cell surface area, a doubling of plasmalemma vesicular density, and an increase in cell volume. Minor morphological changes were observed in epithelial cells. Edema did not affect the total plasmalemma amount of PKC, beta-tubulin, and caveolin-1, but alpha-tubulin and CD-31 increased. In edema, the distribution of these proteins changed between the detergent-resistant fraction of the plasma membrane (DRF, lipid microdomains) and the rest of the plasma membrane [high-density fractions (HDFs)]. PKC and tubulin isoforms shifted from the DRF to HDFs in edema, whereas caveolin-1 increased in DRF at the expense of a decrease in phosphorylated caveolin-1. The changes in cellular morphology and in plasma membrane composition suggest an early endothelial response to mechanical stimuli arising at the interstitial level subsequently to a modest (approximately 5%) increase in extravascular water.
