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.     

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.     

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.     

Fractal analysis of cytoskeleton rearrangement in cardiac muscle during head-down tilt

Thomason, Donald B., Otis Anderson III, and Vandana Menon.Fractal analysis of cytoskeleton rearrangement in cardiac muscleduring head-down tilt. J. Appl.Physiol. 81(4): 1522-1527, 1996.Head-down tiltby tail suspension of the rat produces a volume, but not pressure, loadon the heart. One response of the heart is cytoskeleton rearrangement,a phenomenon commonly referred to as disruption. In these experiments,we used fractal analysis as a means to measure complexity of themicrotubule structures at 8 and 18 h after imposition of head-downtilt. Microtubules in whole tissue cardiac myocytes were stained withfluorescein colchicine and were visualized by confocal microscopy. Thefractal dimensions (D) of thestructures were calculated by the dilation method, which involvessuccessively dilating the outline perimeter of the microtubulestructures and measuring the area enclosed. The head-down tilt resultedin a progressive decrease in D(decreased complexity) when measured at small dilations of theperimeter, but the maximum D (maximumcomplexity) of the microtubule structures did not change withtreatment. Analysis of the fold change in complexity as a function ofthe dilation indicates an almost twofold decrease in microtubulecomplexity at small kernel dilations. This decrease in complexity isassociated with a more Gaussian distribution of microtubule diameters,indicating a less structured microtubule cytoskeleton. We interpretthese data as a microtubule rearrangement, rather than erosion, becausetotal tubulin fluorescence was not different between groups. Thisconclusion is supported by F-actin fluorescence data indicating adispersed structure without loss of actin.

     

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.     

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.     

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.     

Cardiorespiratory responses of animals to passive orthostasis after intermittent hypoxia during head-down tilt

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.     

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.     

Effect of head-down tilt on brain water distribution

Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T2 magnetic resonance imaging. We obtained T2 images of sagittal slices from five subjects while they were supine and during -13 degrees HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.     

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     

Reduced orthostatic tolerance following 4 h head-down tilt

The cardiovascular responses to a 10-min 1.22 rad (70 degrees) head-up tilt orthostatic tolerance test (OST) was observed in eight healthy men following each of a 5-min supine baseline (control), 4 h of 0.1 rad (6 degrees) head-down tilt (HDT), or 4 h 0.52 rad (30 degrees) head-up tilt (HUT). An important clinical observation was presyncopal symptoms in six of eight subjects following 4 h HDT, but in no subjects following 4 h HUT. Immediately prior to the OST, there were no differences in heart rate, stroke volume, cardiac output, mean arterial pressure and total peripheral resistance for HDT and HUT. However, stroke volume and cardiac output were greater for the control group. Mean arterial pressure for the control group was less than HDT but not HUT. Over the full 10-min period of OST, the mean arterial pressure was not different between groups. Heart rate increased to the same level for all three treatments. Stroke volume decreased across the full time period for control and HDT, but only at 3 and 9 min for HUT. There was a higher total peripheral resistance in the HDT group than control or HUT. The pre-ejection period to left ventricular ejection time ratio was less in HDT than for control or HUT groups. These data indicate a rapid adaptation of the cardiovascular system to 4 h HDT that appears to be inappropriate on reapplication of a head to foot gravity vector. We speculate that the cause of the impaired orthostatic tolerance is decreased tone in venous capacitance vessels so that venous return is inadequate.     

Changes in microvascular fluid filtration capacity during 120 days of 6 degrees head-down tilt.

We used venous congestion strain gauge plethysmography (VCP) to measure the changes in fluid filtration capacity (K(f)), isovolumetric venous pressure (Pv(i)), and blood flow in six volunteers before, on the 118th day (D118) of head-down tilt (HDT), and 2 days after remobilization (Post). We hypothesized that 120 days of HDT cause significant micro- and macrovascular changes. We observed a significant increase in K(f) from 3.6 +/- 0.4 x 10(-3) to 5.7 +/- 0.9 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1) (+51.4%; P < 0.003), which returned to pretilt values (4.0 + 0.4 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1)) after remobilization. Similarly, Pv(i) increased from 13.4 +/- 2.1 mmHg to 28.9 +/- 2.8 mmHg (+105.8%; P < 0.001) at D118 and was not significantly different at Post (12.4 +/- 2.6 mmHg). Blood flow decreased significantly from 2.3 +/- 0.3 to 1.3 +/- 0.2 ml. min(-1). 100 ml tissue(-1) at D118 and was found elevated to 3.4 +/- 0.7 ml. min(-1). 100 ml tissue(-1) at Post. We believe that the increased K(f) is caused by a higher microvascular water permeability. Because this may result in edema formation, it could contribute to the alterations in fluid homeostasis after exposure to microgravity.     

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.     

头低位卧床期间人体肠道益生菌多样性变化

目的观察了解头低位卧床期间人体肠道益生菌双歧杆菌属、乳酸杆菌属的数量及多样性的变化趋势。方法采集受试者-6°头低位连续卧床30d期间肠道便样,通过平板可培养技术、浓度梯度凝胶电泳技术和Ion Torrent基因组测序技术平台等实验方法,检测分析肠道粪便益生菌。结果卧床期间,可培养肠道菌群中的双歧杆菌、乳杆菌数量显著减少,益生菌中双歧杆菌出现不规律的缺失与恢复,肠道菌群多样性指数下降。结论头低位卧床期间肠道益生菌多样性发生了改变。益生菌数量减少,多样性指数下降,头低位卧床对肠道菌群有不利的影响。     

Energy and substrate metabolism during a 42-day bed-rest in a head-down tilt position in humans

Microgravity-induced changes in body composition (decrease in muscle mass and increase in fat mass) and energy metabolism were studied in seven healthy male subjects during a 42-day bed-rest in a head-down tilt (HDT) position. Resting energy expenditure (REE), fat and glucose oxidation were estimated by indirect calorimetry on days 0, +8 and +40 of the HDT period. Assessments were performed both in post-absorptive conditions and following two identical test meals given at 3-h intervals. Body composition (dual x-ray absorptiometry) was measured on days 0, +27, +42. Mean post-absorptive lipid oxidation decreased from 53 (SEM 8) mg · min⁻¹ (day 0) to 32 (SEM 10) mg · min⁻¹ (day 8, P=0.04) and 36 (SEM 8) mg · min⁻¹ (day 40, P=0.06). Mean post-absorptive glucose oxidation rose from 126 (SEM 15) mg · min⁻¹ (day 0) to 164 (SEM 14) mg · min⁻¹ (day 8, P=0.04) and 160 (SEM 20) mg · min⁻¹ (day 40, P=0.07). Mean fat-free mass (FFM) decreased between days 0 and 42 [58.0 (SEM 1.8) kg and 55.3 (SEM 1.7) kg, P<0.01] while fat mass increased without reaching statistical significance. The mean REE decreased from 1688 (SEM 50) kcal · day⁻¹ to 1589 (SEM 42) kcal · day⁻¹ (P=0.056). Changes in REE were accounted for by changes in FFM. Mean energy intake decreased from 2532 (SEM 43) kcal · day⁻¹ to 2237 (SEM 50) kcal · day⁻¹ (day 40, P<0.01) with only a minor decrease in the proportion of fat. We concluded that changes in fat oxidation at the whole body level can be found during HDT experiments. These changes were related to the decrease in FFM and could have promoted positive fat balance hence an increase in fat mass. Accepted: 26 March 1998