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The possibility of using intermittent hypoxic training for stimulation of physiological mechanisms underlying the compensatory hemodynamic reactions to orthostatic load was studied in animal experiments. Intermittent hypoxic training had a favorable impact on circulatory reactions, which manifested in stabilization of blood pressure and heart filling pressure and in a decrease in orthostatic hypotension during the initial period of orthostasis. We hypothesized that the positive effect of intermittent hypoxic training on the correction of negative hemodynamic shifts is determined by the training effect aimed at the increase in the vascular tone and venous return to the heart. These results can serve as validation for preventive use of intermittent hypoxic training for reducing blood draining in the lower part of the body, correction of the compensatory orthostatic reaction of the circulatory system, and hence, for improvement of orthostatic resistance.

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The ventilatory response to isocapnic hypoxia was studied using rebreathing techniques in anesthetized and tracheostomized rats both in supine and in head-down tilt position (HDT-30 degrees). Hypoxic responses were calculated by the slope of ventilation against end tidal P(A)O2. The end-tidal P(A)CO2 was kept constant by varying expired gas flow through a CO2-absorbing bypass. The rebreathing was continued until P(A)O2 had fallen to between 70 +/- 3 and 50 +/- 2 mm Hg. The obtained results demonstrated that the maximal minute lung ventilation was 269 +/- 30 % during rebreathing test in supine position and 117 +/- 21% in the head-down tilt. It was also shown that the slopes of the relationship between minute ventilation and the decrease of end tidal P(A)O2 was 3-fold greater in supine than in HDT. The body position seems to affect the ventilatory response to isocapnic progressive hypoxia. In general, it may be a result of hemodynamic conditions alteration which increased respiratory resistive loads, changed the functional condition of carotid hemoreceptors and baroreceptor activity that modulate ventilatory response to chemoreceptor stimulation.

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The role of lung receptors in respiratory control during acute head-down tilt (AHDT, -30 degrees) was investigated in anesthetized, tracheostomized rats. The results show that AHDT increased the mechanical respiratory load, slowed inspiratory flow, reduced the end expiratory lung volume, tidal volume and minute ventilation. On the other hand, during AHDT a significant rise in inspiratory swings of oesophageal pressure was recorded indicated a compensatory increase in inspiratory muscle contraction force. These effects were reduced after transaction of the vagus nerve. It was also shown that respiratory response on added mechanical load was reduced during AHDT as compared with the value in horizontal position. This deference disappeared after vagotomy. The data obtained suggested that afferent information from lung receptors take part in compensation of respiratory effects of AHDT. The cause of reduction in respiratory response to loading during AHDT involves weakness of lung reflexes evoked by volume changes.

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Cardiorespiratory responses induced by upright tilt before and after intermittent hypoxia during head-down tilt, were investigated in rabbits. Arterial blood pressure, heart rate, central venous pressure, transmural filling pressure of the heart (calculated as the product of esophageal and central venous pressure), breathing frequency, esophageal pressure were measured in supine (baseline), head-down and upright posture. Our results indicate a reduction in orthostatic responses in cardiovascular system after intermittent hypoxia.

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In ground-based model of the hemodynamics effects of weightlessness, the intersystem relation of breathing and circulation was investigated during inspiration and expiration separately in anesthetized catz. It's shown that the dynamics of central venous pressure, esophageal pressure and filling pressure of the heart during inspiration in supine and head-down tilt position has obvious similarity to those which hypothetically can be present in microgravity. The results suggest that intrathoracic hemodynamics during inspiration in supine and head-down position may be an adequate ground model for investigation of weightlessness influences on intrathoracic circulation.

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The effects of long-term (21 days) head-down (-30 degrees) hypokinesia (HDH) on respiratory system and a functional state of diaphragm were investigated in rats. Minute ventilation, oesophageal and abdominal pressure, integrated electrical activity of diaphragm were measured in control and experimental group (after 21 days of HDH) of animals. The measurements were made in several body positions atresting and in occlusion breathing. The results indicate that HDH causes reduction in minute ventilation of lungs, decrease in orthostatic stability and functional reserve of the respiratory system capacity. It was established that the basic mechanism of HDH respiratory effects is contractile failure of diaphragm related to damage in excitation-contraction coupling in its muscular fibres.

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A new method for mitigation of the negative consequences of blood shift toward the cranial end as a result of simulation of the hemodynamic effects of microgravity (head-down tilt at -6 degrees) combines the lower body negative pressure (LBNP) and negative pressure respiration (NPR) to accelerate blood outflow from cerebral vessels and, additively, to restrain blood inflow from the lower body. The longitudinal hydrostatic pressure gradient is thus reproduced but main hemodynamic parameters assume values characteristic of the vertical posture. The objective was to compare the strength of LBNP and LBNP + NRP training in preventing orthostatic disorders following 7-d HDT. Subjects were 6 male volunteers aged 24 to 40 yrs. In the control experiment, every subject experienced episodes of orthostatic disorders. In the second experiment (LBNP), 4 subjects were afflicted; in the third experiment (LBNP + NPR), orthostatic disorders were minor, if at all. Absence of profound hemodynamic, autonomic or pre-syncope symptoms leads to the conclusion that combination LBNP + NPR is a more favorable preventive method than discrete LBNP.

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The focus was placed on the physiological mechanisms of correction of the blood redistribution during the head-down tilt (HDT) with a discrete or complex use of the methods of negative pressure respiration (NPR) and lower body negative pressure (LBNP). It was evidenced that rise in the intracranial hydrostatic pressure in HDT (-6 degrees) can be compensated by NPR within a range of -10 to -15 cm of water column causing decrease in the intrasternal pressure from -5.04 to -7.74 cm w.c. Bioimpedance and ultrasonic investigations led to the conclusion that the decreased transpulmonary pressure is responsible for blood outflow from the intracranial venous system till the level adequate to the horizontal position of the body. The results were verified in experiments with unconscious cats: pressure in the exterior jugular vein and v. cava superior during HDT (-30 degrees) with NRP at -5 cm w.c. decreased by 3.2. and 4.3. w.c., respectively. Experiments with human subjects also demonstrated that the complex use of NPR and LBNP produces an additive hemodynamic effect and can be considered a new method for correcting the adverse consequences of redistribution of the local blood volumes toward the head end.

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Changes in the ratio between intrathoracic and central venous pressure were studied in narcotized cats under conditions of constant positive or negative pressure ventilation. Transformation of elastic characteristics in the respiratory system caused by changes in intrathoracic pressure led to inversion of the ratio between transpulmonary intrathoracic and central venous pressure determining right atrial filling pressure.

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Abdominal and thoracic functional reserves of respiration and level of their involvement in spontaneous breathing were investigated in 10 male volunteers aged 20 to 22 put in horizontal head-down (-7 degrees and -30 degrees) or orthostatic (+70 degrees) position. The thoracic-abdominal functional reserves of respiration dependent on the spatial positioning of the body were found to be the factor that determines magnitude of contribution of the thorax and diaphragm in the breathing volume.

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In experiments with anesthetized cats effects of breathing under negative pressure (BNP, -5 cm of water column) combined with lower body negative pressure (LBNP, -20 cm of water column) on the cardiorespiratory reactions to postural simulation of the hemodynamic shifts in microgravity were studied. Evidence was obtained that this complex barometric exposure of tilted animals (-30 degrees) imitated the central and peripheral hemodynamics characteristic of tilt at the calculated inclination of +6 degrees up to +12 degrees. Extrapolation of the experimental data on the orthodox physiological model of microgravity (HDT, -6 degrees) allows an assumption that the protocol of complex barometric exposure tested in this experiment transforms the hemodynamic parameters under study to the levels close to those in the vertical body. Results of the investigation infer an additive character of the complex barometric exposure (LBNP + BNP) and its utility as a model of orthostatic g-loads.

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Proposed is a modified method to counteract the headword redistribution of local blood volumes in microgravity by discrete or combined exposure to respiration at negative pressure (RNP) and lower body negative pressure (LBNP). Physically and physiologically substantiated levels of the barometric influences on the central and peripheral hemodynamics to approximate the normal gradients of blood hydrostatic pressure along the body axis are given. Discrete RNP applied to test-subjects during HDT was shown to return the cerebral and cervical hemodynamic parameters to levels determined in horizontal position. Combination of RNP and LBNP had additive character as it advantaged the recovery of values characteristic of the orthostatic position. There are technical possibilities to integrate the LBNP and RNP devices for the benefit of scientific, certification, predictive, and training objectives of space biomedicine.

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To improve methods of offsetting the hemodynamic shifts in microgravity, applicability of breathing at negative pressure (BNP, pressure relief by -5.0 cm of water column) during inspiration and expiration was assessed in acute experiments with unconscious cats tilted head-down (-30 degrees). Direct measurement of pressure in v. cava superior and v. jugularis externa using a catheter revealed a concurrent significant (p < 0.05) growth of the parameter which should be considered a sign of impeded venous outflow from the craniocervical vessels. BNP added to the sucking effect of the thoracic cavity (the siphoning effect) and led to more massive venous outflow from cephalic vessels as evidenced by pressure drop in the jugular vein and v. cava superior to the values determined in the basic horizontal position. However, BNP did not significantly alter arterial hemodynamics, respiration pattern or gas exchange. Data of the investigation attest effectiveness of this method of moderating blood flow to the cat's head during HDT and possibility to apply it in the zero-g environment.

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In anaesthetised cats, antiorthostatic posture of the body with an inclination angle of 30 degrees increased pressure in the vena cava superior and in jugular vein. The rest of the cardio-respiratory parameters were changed insignificantly. Physical and physiological mechanisms of the blood regional redistribution in alteration of the body gravitation orientation, are discussed.

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Validity of the hypothesis for the role of the respiratory muscles in deterioration of physical work capacity following long-term hypokinesia was tested. Experiments were performed with participation of 8 female subjects aged from 27 to 36 years in the 120-day head-down bed rest. Physical performance and functional status of the respiratory muscles have been determined during incremental loading on bicycle ergometer with normal respiration and breathing against additional external resistance. Functional deficit of the respiratory muscles due to long-term bed rest was shown not to allow adequate ventilation and gas exchange at submaximal loads. This resulted in dyspnea, hypoventilation-induced decrease in oxygen consumption and carbon dioxide release, hypercapnia, and lowered threshold of anaerobic metabolism which, in parallel with the deconditioning of the cardiovascular system and the skeletal anti-g musculature, were responsible for degradation of aerobic physical work capacity.

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According to the previous study [2], simulation of the physiological effects of weightlessness leads to deconditioning of the respiratory muscles which, in its turn, may be a factor impacting the aerobic working capacity. In the present work the experimental findings laid the basis for a physiological concept for medical/engineering requirements to countermeasures against deconditioning of the respiratory muscles, designing and laboratory and physiological testing of a prototype of training loading vest Elastik-R. The vest was shown to enhance speed and force qualities of the respiratory muscles in training athletes, to improve ventilation and gas-exchange functions of the lung, and to increase physical performance and aerobic capacity. Recommendations on utilization of the Elastik-R vest during space flight have been issued.

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Literature data and results of our own studies into an effect of micro- and macro-gravity on an external respiration function of man are presented. It is found that in cosmonauts following the 7-366 day space missions there is an enhanced tendency associated with an increased flight duration toward a decrease in the lung volume and breathing mechanics parameters: forced vital capacity of the lungs FVC) by 5-25 percent, peak inspiratory and expiratory (air) flows (PIF, PEF) by 5-40 percent. A decrease in FVC appears to be explained by a new balance of elastic forces of the lungs, chest and abdomen occurring in microgravity as well as by an increased blood filling and pulmonary hydration. A decline of PIF and PEF is probably resulted from antigravitational deconditioning of the respiratory muscles with which a postflight decreased physical performance can in part be associated. The ventilation/perfusion ratios during orthostasis and +Gz and +Gx accelerations are estimated. The biophysical nature of developing the absorption atelectases on a combined exposure to accelerations and 100% oxygen breathing is confirmed. A hypothesis that hypervolemia and pulmonary congestion can increase the tendency toward the development of atelectases in space in particular during pure oxygen breathing is suggested. Respiratory physiology problem area which is of interest for space medicine is defined.

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