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 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.     

Neuromuscular adaptations during 30 days of cast-immobilization and head-down bedrest

Prolonged skeletal muscle disuse, during space flights and on Earth, produces distinct adaptive changes in the neuromuscular system of human subjects. There is a significant decline in muscle mass and strength, exercise capacity, fatigue resistance, integrated EMG (IEMG) output and time-dependent alterations in the behavior of Hoffman (H) and deep tendon reflexes. The objective of this study was to examine the changes in excitability of segmental motoneuronal network and its influence upon gastrocnemius-soleus (G-S) function in healthy male and female subjects, who underwent either 6 degrees head-down bedrest (HDB) or unilateral cast-immobilization (CIM) for a period of 30 days.     

Ultrasound measurement of transcranial distance during head-down tilt

Exposure to microgravity elevates blood pressure and flow in the head, which may increase intracranial volume (ICV) and intracranial pressure (ICP). Rhesus monkeys exposed to simulated microgravity in the form of 6 degrees head-down tilt (HDT) experience elevated ICP. With humans, twenty-four hours of 6 degrees HDT bed rest increases cerebral blood flow velocity relative to pre-HDT upright posture. Humans exposed to acute 6 degrees HDT experience increased ICP, measured with the tympanic membrane displacement (TMD) technique. Other studies suggest that increased ICP in humans and cats causes measurable cranial bone movement across the sagittal suture. Due to the slightly compliant nature of the cranium, elevation of ICP will increase ICV and transcranial distance. Currently, several non-invasive approaches to monitor ICP are being investigated. Such techniques include TMD and modal analysis of the skull. TMD may not be reliable over a large range of ICP and neither method is capable of measuring the small changes in intracranial volume that accompany changes in pressure. Ultrasound, however, may reliably measure small distance changes that accompany ICP fluctuations. The purpose of our study was to develop and evaluate an ultrasound technique to measure transcranial distance changes during HDT.     

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.     

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.     

Temporal artery flow response during the last minute of a head up tilt test, in relation with orthostatic intolerance after a 60 day head-down bedrest

Objective

Check if the Temporal flow response to Tilt could provide early hemodynamic pattern in the minutes preceding a syncope during the Tilt test performed after a 60-d head down bedrest (HDBR).

Method

Twenty-one men divided into 3 groups [Control (Con), Resistive Vibration (RVE) and Chinese Herb (Herb)] underwent a 60 day HDBR. Pre and Post HDBR a 20 min Tilt identified Finishers (F) and Non Finishers (NF). Cerebral (MCA), Temporal (TEMP), Femoral (FEM) flow velocity, were measured by Doppler during the Tilt. Blood pressure (BP) was measured by arm cuff and cardiopress.

Results and Discussion

Four of the 21 subjects were NF at the post HDBR Tilt test (Con gr:2, RVE gr: 1, Herb gr: 1). At 1 min and 10 s before end of Tilt in NF gr, FEM flow decreased less and MCA decreased more at post HDBR Tilt compared to pre (p<0.05), while in the F gr they changed similarly as pre. In NF gr: TEMP flow decreased more at post HDBR Tilt compared to pre, but only at 10 s before the end of Tilt (P<0.05). During the last 10 s a negative TEMP diastolic component appeared which induced a drop in mean velocity until Tilt arrest.

Conclusion

The sudden drop in TEMP flow with onset of a negative diastolic flow preceding the decrease in MCA flow confirm that the TEMP vascular resistance respond more directly than the cerebral one to the cardiac output redistribution and that this response occur several seconds before syncope.     

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans.

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.     

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.     

Venous distensibility and venous emptying in the legs during a 42-day -6 degrees head-down bedrest

Exposure to actual or simulated microgravity is known to result in changes in lower limb venous compliance or distensibility which may play a role in post-bedrest or postflight orthostatic intolerance. Venous deconditioning has only been described in terms of changes in vascular compliance or distensibility. But a complete understanding of changes in venous hemodynamics and cardiovascular regulation occurring under these conditions has to take into account changes in emptying capacities of the veins which influence venous return, cardiac filling, and cardiac output regulation. Moreover, few data are available about the course of changes in venous hemodynamics for periods of simulated microgravity longer than 4 weeks. The purpose of this investigation was to measure parameters of venous compliance and venous emptying before, during, and after a 42-day period of bedrest at -6 degrees head-down tilt for a better understanding of long term venous physiological adaptation to microgravity.     

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     

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.     

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.     

The effect of dDAVP with saline loading on fluid balance during LBNP and standing after 24-hr head-down bedrest

Shuttle astronauts currently drink approximately a quart of water with eight salt tablets before reentry to restore lost body fluid and thereby reduce the likelihood of cardiovascular instability and syncope during reentry and after landing. However, the saline loading countermeasure is not entirely effective in restoring orthostatic tolerance to preflight levels. We tested the hypothesis that the effectiveness of this countermeasure could be improved with the use of a vasopressin analog, 1-deamino-8-D-arginine vasopressin (dDAVP). The rationale for this approach is that reducing urine formation with exogenous vasopressin should increase the magnitude and duration of the vascular volume expansion produced by the saline load, and in so doing improve orthostatic tolerance during reentry and postflight.     

Haemodynamics of leg veins during a 30-days-6 degrees head-down bedrest with and without lower body negative pressure

Venous distensibility of the lower limbs was assessed in six healthy men who were submitted twice successively to 1 month of -6 degrees head-down bedrest, with and without lower body negative pressure (LBNP) (LBNP subjects and control subjects, respectively). Venous capacity (delta Vv,max, in ml.100 ml-1) of the legs was determined by mercury strain gauge plethysmography with venous occlusion. Plethysmographic measurements were made on each subject before (Dc), during (D6 and D20) and after (5th day of recovery, D+5) bedrest. During bedrest, LBNP was applied daily, several times a day to the subjects submitted to this procedure. Results showed a gradual increase in Vv,max (ml.100 ml-1) throughout the bedrest, both in the control group [delta Vv,max = 2.11 SD 0.54 at Dc, 2.69 SD 0.29 at D6, 4.39 SD 2.08 at D20, 2.39 SD 0.69 at D+5, P less than 0.001 (ANOVA)] and in the LBNP group [delta Vv,max = 2.07 SD 0.71 at Dc, 2.85 SD 1.19 at D6, 3.75 SD 1.74 at D20, 2.43 SD 0.94 at D+5, P less than 0.001 (ANOVA)], without significant LBNP effect. These increases were of the same order as those encountered during spaceflight. It is concluded that -6 degrees head-down bedrest is a good model to simulate the haemodynamic changes induced by exposure to weightlessness and that LBNP did not seem to be a good technique to counteract the adverse effects of weightlessness on the capacitance vessels of the lower limbs. This latter conclusion raises the question of the role and magnitude of leg venous capacitance in venous return and cardiac regulation.     

Effect of space flight and head-down bedrest on neuroendocrine response to metabolic stress in physically trained subjects

The aim of this study was to evaluate the association of plasma epinephrine (EPI) and norepinephrine (NE) responses to insulin induced hypoglycemia (ITT) 3 weeks before the space flight (SF), on the 5th day of SF, on the 2nd and 16th days after the landing in the first Slovak astronaut, and before and on the 5th day of prolonged subsequent head-down (-6 degrees) bed rest (BR) in 15 military aircraft pilots. Blood samples during the test were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Insulin hypoglycemia was induced by i.v. administration of 0.1 IU/kg BW insulin (Actrapid HM) in bolus. Insulin administration led to a comparable hypoglycemia in pre-flight, in-flight conditions and before and after bed rest. ITT led to a pronounced increase in EPI levels and moderate increase in NE in pre-flight studies. However, an evidently reduced EPI response was found after insulin administration during SF and during BR. Thus, during the real microgravity in SF and simulated microgravity in BR, insulin-induced hypoglycemia activates the adrenomedullary system to less extent than at conditions of the Earth gravitation. Post-flight changes in EPI and NE levels did not significantly differ from those of pre-flight since SF was relatively short (8 days) and the readaptation to Earth gravitation was fast. It seems, that an increased blood flow in brain might be responsible for the reduced EPI response to insulin. Responses to ITT in physically fit subjects indicate the stimulus specificity of deconditioning effect of 5 days bed rest on stress response. Thus, the data indicate that catecholamine responses to ITT are reduced after exposure to real as well as simulated microgravity.     

Histological examination on edema formation in the rabbit brain exposed to head-down tilt

Previous studies demonstrated that exposure to simulated microgravity, head-down tilt (HDT), caused cephalad fluid shift, increased capillary pressure in the head, and produced facial edema and nasal congestion. It is also known that exposure to HDT affects hemodynamics in the brain. Cerebral blood flow (CBF) velocity increases for at least 6 hours after the onset of 6 degrees HDT in humans. Intracranial pressure (ICP) elevates during 6 degrees HDT in humans and monkeys. However, there is little information regarding edema formation in the brain due to HDT except a morphological study reported by Kaplansky and colleagues who showed that perivascular edema occurred in the monkey brain after 7 days of 6 degrees HDT. Thus, it is interesting to examine whether edema formation occurs in the other animal model for simulation of microgravity, since several factors such as the duration of HDT, angle of HDT, and species difference may affect the result. In the present study, formation of brain edema was investigated by histological examinations in rabbits exposed to 45 degrees HDT for 2 days or 8 days. We hypothesized that HDT causes brain edema which can be demonstrated as extravasation of plasma constituents and histological changes.     

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.     

Effects of LBNP + specific physical exercises on leg venous hemodynamics during a 28-days -6 degrees head-down bedrest

The mechanisms underlying increased venous distensibility during exposure to microgravity are not well known yet. However, there seems to be evidence indicating that skeletal muscle changes resulting from exposure to microgravity play a very important role. The purpose of this experiment was to test the hypothesis that leg muscles could play an important role in the changes of leg venous distensibility observed in simulated microgravity. Twelve subjects were submitted for 28 days to a -6 degrees head-down bedrest. Changes in leg vein hemodynamics (filling and emptying) have been measured by mercury strain gauge plethysmography with venous occlusion. Six of these subjects trained their lower limbs with isometric and isokinetic exercises during bedrest (group CM), while the other 6 subjects (control group, C) had no training.