Ventilatory response to hypercapnia during head-down tilt

The effect of hypercapnic ventilatory response was examined in anaesthetized spontaneously breathing rats by using rebreathing techniques both at supine and -30 degrees head-down tilt positions. No significant differences were found in the minute ventilation response between the supine and head-down positions during hypercapnic stimulations. In contrast, we found that hypercapnia-stimulated breathing affected the relationship between deltaPoes and deltaP(ET), CO2. This study demonstrates that higher peak deltaPoes was developed in order to maintain the same ventilation in the supine and head-tilt position. The higher deltaPoes/deltaP(ET), CO2 head-down ratio than the supine was a result of increased airflow impedance of the total respiratory system while head-down. It is concluded that ventilation at head-down is regulated in such a way as to maintain the pH and Paco, despite mechanical loading imposed by the environment. Hence, during hypercapnic stimulation the ventilatory response in head-down position is shaped by interaction of chemical drives and mechanical afferent information arising.     

Dynamic cerebral autoregulation is preserved during acute head-down tilt.

Complete ganglion blockade alters dynamic cerebral autoregulation, suggesting links between systemic autonomic traffic and regulation of cerebral blood flow velocity. We tested the hypothesis that acute head-down tilt, a physiological maneuver that decreases systemic sympathetic activity, would similarly disrupt normal dynamic cerebral autoregulation. We studied 10 healthy young subjects (5 men and 5 women; age 21 +/- 0.88 yr, height 169 +/- 3.1 cm, and weight 76 +/- 6.1 kg). ECG, beat-by-beat arterial pressure, respiratory rate, end-tidal CO2 concentration, and middle cerebral blood flow velocity were recorded continuously while subjects breathed to a metronome. We recorded data during 5-min periods and averaged responses from three Valsalva maneuvers with subjects in both the supine and -10 degrees head-down tilt positions (randomized). Controlled-breathing data were analyzed in the frequency domain with power spectral analysis. The magnitude of input-output relations were determined with cross-spectral techniques. Head-down tilt significantly reduced Valsalva phase IV systolic pressure overshoot from 36 +/- 4.0 (supine position) to 25 +/- 4.0 mmHg (head down) (P = 0.03). Systolic arterial pressure spectral power at the low frequency decreased from 5.7 +/- 1.6 (supine) to 4.4 +/- 1.6 mmHg2 (head down) (P = 0.02), and mean arterial pressure spectral power at the low frequency decreased from 3.3 +/- 0.79 (supine) to 2.0 +/- 0.38 mmHg2 (head down) (P = 0.05). Head-down tilt did not affect cerebral blood flow velocity or the transfer function magnitude and phase angle between arterial pressure and cerebral blood flow velocity. Our results show that in healthy humans, mild physiological manipulation of autonomic activity with acute head-down tilt has no effect on the ability of the cerebral vasculature to regulate flow velocity.     

Renal responsiveness to aldosterone during exposure to head-down tilt bedrest

The kidneys represent a fundamental organ system responsible in part for the control of vascular volume. A 10% to 20% reduction in plasma volume is one of the fundamental adaptations during exposure to low gravity environments such as bedrest and space flight. Bedrest-induced hypovolemia has been associated with acute diuresis and natriuresis. Elevated baseline plasma renin activity and aldosterone levels have been observed in human subjects following exposure to head-down tilt and spaceflight without alterations in renal sodium excretion. Further, attempts to restore plasma volume with isotonic fluid drinking or infusion in human subjects exposed to head-down bedrest have failed. One explanation for these observations is that renal distal tubular cells may become less sensitive to aldosterone following exposure to head-down tilt, with a subsequent reduction in renal capacity for sodium retention. We hypothesized that elevated sodium and water excretion observed during prolonged exposure to bedrest and the subsequent inability to restore body fluids by drinking might be reflected, at least in part, by reduced renal tubular responsiveness to aldosterone. If renal tubular responsiveness to aldosterone were reduced with confinement to bedrest, then we would expect measures of renal sodium retention to be reduced when a bolus of aldosterone was administered in head-down tilt (HDT) bedrest compared to a control experimental condition. In order to test this hypothesis, we conducted an investigation in which we administered an acute bolus of aldosterone (stimulus) and measured responses in renal functions that included renal clearances of sodium and free water, sodium/potassium ratio in urine, urine sodium concentration, and total and fractional renal sodium excretion.     

Changes of intracranial pressure during head-down tilt in anesthetized and conscious rabbits

Effects of head-down tilt on intracranial pressure were studied in anesthetized and conscious rabbits. Adult Japanese white rabbits of both sexes, weighing 2.5-3.5 kg, were used in the experiments. Experiment 1. Animals were anesthetized with pentobarbital, and ICP was monitored through a catheter inserted into the subarachnoid space. ICP elevated immediately after the onset of 45 degrees HDT and gradually reduced toward the baseline level in the next 8 hours. Experiment 2. Each rabbit was exposed to 45 degrees HDT for 24 hours and the ICP was measured through a catheter which had been implanted 7 days before. In the conscious rabbits, ICP increased about 4 mmHg after the onset of 45 degrees HDT, further increased gradually to the peak at 11 hours of HDT, and then started to return to the baseline. These results suggest that the time course of the change in ICP during HDT is considerably different between anesthetized and conscious rabbits.     

The role of lung afferent system in respiratory control during head-down tilt

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.     

Mechanisms of the decrease in human postural stability during prolonged head-down tilt

In 3 identical experiments with head-down bed rest lasting 60, 90, and 120 days and involving 18 volunteers, dynamics of the development of cardiovascular system (C.V.S) deconditioning was studied. A set of radioisotopic research techniques was used. Volumes of hemocirculation, body fluids, and metabolic activity of the bone marrow were investigated. Functions of the central and peripheral hemodynamics were studied. To determine the extent of C.V.S. deconditioning during the baseline period, on days 60, 90, and 120 of hypokinesia and during recovery, an orthostatic test was performed. The degree of gravitational blood shifting in regions (the head, thorax, the abdomen, the lower extremities) was recorded. Critical thresholds of blood shifting in the body were determined. It was established that the blood pooled in the splanchnic region participates in the decrease of central hypovolemia. Because of the insufficient number of observations, this research should be continued. During recovery, the sign of (CVS) deconditioning noted demonstrated a clear tendency to normalization.     

Augmentation of the push-pull effect by terminal aortic occlusion during head-down tilt.

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the "push-pull effect." The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90 degrees head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90 degrees head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 +/- 1.3, -23 +/- 0.7, and -28 +/- 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences (P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.     

Leg blood flow during slow head-down tilt with and without leg venous congestion

The effects of slow changes in body position on leg blood flow (LBF) were studied in nine healthy male subjects. Using a tilt table, sitting volunteers were tilted about 60° backwards to a supine position within 40 s. To modify the venous filling in the legs, the tilt manoeuvre was repeated with congestion of the leg veins induced by two thigh cuffs inflated to a subdiastolic pressure of 60 mmHg. Doppler measurements in the femoral artery were used to estimate LBF. Additional Doppler measurements at the aortic root in five of the subjects were taken for the determination of cardiac output. The LBF was influenced by body position. In the control experiment it increased from 500 ml · min⁻¹ in the upright to 780 ml · min^–1 after 15 min in the supine position. A mean maximal value of 950 ml · min⁻¹ was observed 20 s after the tilt. Heart rate remained almost constant during the tilt phase, whereas stroke volume increased from 90 ml to 120 ml and it remained at that level after the cessation of the tilt. Congestion of the leg veins had no significant effect on heart rate, stroke volume and mean blood pressure. However, it increased vascular resistance of the leg during and after the tilt. After 15 min in the tilted position LBF amounted to 600 ml · min⁻¹. The results suggest that the filling of the leg veins is inversely related to leg blood flow. The most likely mechanism underlying this observation is a local effect of venous filling on vasomotor tone. Accepted: 20 May 1998     

Development of osteoporosis in primates in hypokinesia with head-down tilt

It has been shown earlier that 7-19 day exposure of monkeys to hypokinesia with head-down tilt (HDT) produces osteopenia in their load-bearing bones. The present work continued the investigations of osteopenia dynamics in monkeys which had been under the HDT conditions for 15 and 30 days.     

Physiological reactions of primates to 9-D immersion and head-down tilt

Purpose of the investigation was to compare physiological reactions of primates (Macaca mulatta) to microgravity simulated by immersion and head-down tilt (HDT). In immersion experiments, primates in waterproof suits were put into motion-restraining chairs and immersed into water (t=35.4 degrees C) breast-deep for 9 days. In 9-d HDT experiments, prone primates were motor restrained in dedicated tilt beds at -5 degrees. It was found that the CNS functioning was significantly affected, the plasma volume reduced and the marrow erythropoietic function declined. Atrophy developed in leg muscles on a backdrop of iliopectineal spongy osteopenia. Loss in hydration, inhibition of erythropoietic hemopoiesis and iliopectineal spongy osteopenia were more pronounced following immersion than HDT.     

Effect of head-down tilt on respiratory responses and human inspiratory muscle activity

The effect of a head-down tilt on the responses of the external respiration system and the functional capacity of the diaphragm and parasternal muscles were investigated in 11 healthy subjects. A 30-min head-down tilt posture (−30° relative to the horizontal) significantly increased the inspiratory time, decreased the respiration rate and the inspiratory and expiratory flow rates; and increased the airway resistance compared to these values in the vertical posture. There were no significant changes in tidal volume or minute ventilation. The electromyograms (EMGs) of the diaphragm and parasternal muscles showed that the constant values of tidal volume and minute ventilation during head-down tilt could be provided by an increase in the electric activity of the thoracic inspiratory muscles. It was established that the contribution of the thoracic inspiratory muscles increased, while the diaphragms’ contribution decreased, during patient, spontaneous breathing. The maximal inspiratory effort (Muller’s maneuver) during a head-down tilt evoked the opposite EMG-activity pattern: the contribution of inspiratory thoracic muscles was decreased and the diaphragm EMG activity was increased compared to the vertical posture. These results suggest that coordinated modulations in inspiratory muscle activity make it possible to preserve the functional reserve of human inspiratory muscles during a short-term head-down tilt.     

Effect of head-down tilt on respiratory responses and human inspiratory muscles activity

The effect of head-down tilt on respiration and diaphragmal and parasternal muscles activity was investigated in 11 healthy subjects. The short-time (30 min) head-down tilt posture (-30 degrees relatively horizont) increased the inspiratory time (P < 0.05), decreased breathing frequency (P < 0.05), inspiratory and expiratory flow rate (P < 0.05) and increased the airway resistance (P < 0.05) compared with values in vertical posture. There were no significant changes in tidal volume and minute ventilation. Constant values of tidal volume and minute ventilation during head-down tilt were provided by increasing in EMG activity of parasternal muscles more then twice. It was established that the contribution of chest wall inspiratory muscles increased while the diaphragm's contribution decreased during head-down spontaneous breathing. Maximal inspiratory effort (Muller's maneuver) during head-down tilt evoked the opposite EMG-activity pattern: the contribution of inspiratory thoracic muscles was decreased and diaphragm's EMG-activity was increased compared with vertical posture. These results suggest that coordinate modulations in inspiratory muscles activity allows to preserve the functional possibility of human inspiratory muscles during short-time head-down tilt.     

反复体位改变训练可提高人体头低位耐力

目的检验反复体位改变训练可提高人体头低位耐力的假设是否正确.方法6名青年男性被试者经受了为期11 d、共9次反复体位改变训练.在训练前、后分别评价被试者对-30°/30 min头低位倾斜(head-down tilt,HDT)的反应,记录症状、心率、血压、颈部血流等主客观指标.结果①训练后,被试者在HDT中的反应得到了改善,表现为与训练前相比,HDT中的不良症状明显减轻(症状得分1.00±0.63vs6.00±3.79,P＜0.05),心率降低的幅度明显增加(-4.4±3.6 vx-0.6±2.5,P＜0.01);②训练前,被试者在HDT中,颈内静脉血流与仰卧位比较明显减少(P＜0.01),初期颈内动脉血流明显增加(P＜0.01),颈总动脉血流呈现增加的趋势;训练后,被试者在HDT中,颈内静脉血流与仰卧位比较无显著差别,颈内动脉血流呈现先升后降的趋势,颈总动脉血流呈现降低的趋势.结论反复体位改变训练可提高人体头低位耐力;血液头向转移得到抑制是反复体位改变训练提高头低位耐力的主要机制.     

Renal function of rats in response to 37 days of head-down tilt

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.     

Regulation and distribution of body fluid during a 6-day head-down tilt study in a randomized cross-over design

Head down tilt (-6 degrees HDT) examinations are commonly used simulation models for various microgravity induced changes in body functions. Body fluid distribution (by means of dye dilution and two independent multifrequency impedance techniques), water- and sodium-handling, and the plasma/serum concentrations of fluid balance related hormones have been determined in a randomized, controlled, cross-over study in 8 healthy test subjects. The comparison of responses to HDT and an upright control position with respective experiences from space shows some similarities but also various discrepancies between the terrestrial simulation and real microgravity.     

Body temperature and skin blood flow during a 14-day bed-rest in a head-down tilt position in humans

Exposure to microgravity or simulated microgravity is known to affect regulatory function in autonomic nervous system. With regard to thermoregulation, simulated microgravity impairs sweating and induces lower skin and higher internal temperatures during physical work. During supine rest after HDT bed rest, the internal temperatures were reported to be higher than those of pre-HDT bed rest in some studies but not in others. There is no report about the dynamic changes of skin blood flow during 14-day HDT bed rest. The process of HDT bed-rest deconditioning on the function of the thermoregulatory system is virtually unknown. The HDT induces an immediate cephalad fluid shift which would inhibit the sympathetic outflow through the arterial and cardiopulmonary baroreflexes, which may increase the skin blood flow. On the other hand, prolonged HDT bed rest induces dehydration, which will increase sympathetic outflow through cardiopulmonary baroreceptor modulation. Both sympathetic activation and dehydration itself will decrease skin blood flow. It seems probable that the general effect on skin blood flow may reverse along the HDT bed rest. However, the dynamic characters of skin blood flow and body temperature during the HDT bed rest have not been studied thoroughly. Therefore, the purpose of present study was to investigate the changes of skin blood flow and body temperature during 14 days HDT bed rest.     

Exercise throughout 6 degrees head-down tilt bed rest preserves thermoregulatory responses.

Spaceflight and its bed rest analog [6 degrees head-down tilt (HDT)] decrease plasma and blood volume and aerobic capacity. These responses may be associated with impaired thermoregulatory responses observed during exercise and passive heating after HDT exposure. This project tested the hypothesis that dynamic exercise during 13 days of HDT bed rest preserves thermoregulatory responses. Throughout HDT bed rest, 10 subjects exercised for 90 min/day (75% of pre-HDT maximum heart rate; supine). Before and after HDT bed rest, each subject exercised in the supine position at the same workload in a 28 degrees C room. The internal temperature (Tcore) threshold for the onset of sweating and cutaneous vasodilation, as well as the slope of the relationship between the elevation in Tcore relative to the elevation in sweat rate (SR) and cutaneous vascular conductance (CVC; normalized to local heating maximum), were quantified pre- and post-HDT. Tcore thresholds for the onset of cutaneous vasodilation on the chest and forearm (chest: 36.79 +/- 0.12 to 36.94 +/- 0.13 degrees C, P = 0.28; forearm: 36.76 +/- 0.12 to 36.91 +/- 0.11 degrees C, P = 0.16) and slope of the elevation in CVC relative to Tcore (chest: 77.9 +/- 14.2 to 80.6 +/- 17.2%max/ degrees C; P = 0.75; forearm: 76.3 +/- 11.8 to 67.5 +/- 14.3%max/ degrees C, P = 0.39) were preserved post-HDT. Moreover, the Tcore threshold for the onset of SR (36.66 +/- 0.12 to 36.74 +/- 0.10 degrees C; P = 0.36) and the slope of the relationship between the elevation in SR and the elevation in Tcore (1.23 +/- 0.19 to 1.01 +/- 0.14 mg x cm(-2) x min(-1) x degrees C(-1); P = 0.16) were also maintained. Finally, after HDT bed rest, peak oxygen uptake and plasma and blood volumes were not different relative to pre-HDT bed rest values. These data suggest that dynamic exercise during this short period of HDT bed rest preserves thermoregulatory responses.     

Effect of lower body negative pressure on orthostatic tolerance and cardiac function during 21 days head-down tilt bed rest

The purpose of the present study was to investigate the changes of orthostatic tolerance and cardiac function during 21 d head-down tilt (HDT) bed rest and effect of lower body negative pressure in the first and the last week in humans. Twelve healthy male volunteers were exposed to -6 degrees HDT bed rest for 21 d. Six subjects received -30 mmHg LBNP sessions for 1 h per day from the 1st to the 7th day and from the 15th to the 21st day of the HDT, and six others served as control. Orthostatic tolerance was assessed by means of standard tilt test. Stroke volume (SV), cardiac output (CO), preejection period (PEP) and left ventricular ejection time (LVET) were measured before and during HDT. Before HDT, all the subjects in the two groups completed the tilt tests. After 10 d and 21 d of HDT, all the subjects of the control group and one subject of the LBNP group could not complete the tilt test due to presyncopal or syncopal symptoms. The mean upright time in the control group (15.0 +/- 3.2 min) was significantly shorter than those in the LBNP group (19.7 +/- 0.9 min). SV and CO decreased significantly in the control group on days 3 and 10 of HDT, but remained unchanged throughout HDT in the LBNP group. A significant increase in PEP/LVET was observed on days 3 and 14 of HDT in both groups. The PEP/LVET in the LBNP group was significantly lower on day 3 of HDT, while LVET in the LBNP group was significantly higher on days 3, 7 and 14 of HDT than those in the control group. The results of this study suggest that brief daily LBNP sessions used in the first and the last weeks of 21 d HDT bed rest were effective in diminished the effect of head-down tilt on orthostatic tolerance, and LBNP might partially improve cardiac pumping function and cardiac systole function.     

Evaluation of synthetic antidiuretic hormone as a corrective substance following a head-down tilt

The effects of the administration of desmopressin, a synthesized analog of antidiuretic hormone, together with a water-salt supplement on the renal function and orthostatic stability were investigated. Six healthy men spent 12 h in the head-down tilt (HDT) position. It was demonstrated that administration of desmopressin led to normalization of salt and water homeostasis; moreover, the tolerance of the standard 20 min passive standing test was improved significantly. These observations indicate that intake of the synthetic vasopressin analog combined with water-salt supplement counteracts hypohydration of the body during HDT and improved orthostatic tolerance.     

Comparing cardiovascular responses during exercise between head-down tilt pedaling with lower body negative pressure and upright cycling in man

If lower body negative pressure (LBNP) loaded on exercise in weightlessness environment is able to derive a comparable cardiovascular responses to these in the ground, it should be identified as an optimal LBNP for exercise in space. To investigate the LBNP, 7 young subjects were exercised 4 work rates stepping up every 50 watts from 50 watts to 200 watts every 5 minutes in the upright position or 6 degree head down tilt position with each LBNP of 20, 40, 60, 80, and 100 mmHg. Oxygen uptake during tilt exercise with over 60 mmHg LBNP was not different from it in upright exercise. Heart rate and systolic arterial pressure responses to exercise were very similar between tilt exercise with 60 mmHg LBNP and upright exercise. In conclusion, the optimal LBNP loaded on exercise in space should be around 60 mmHg.