Erythropoietin in blood volume regulation under real and simulated micro-g conditions

Changes in erythropoietin levels in the blood were measured under several experimental conditions. Subjects were exposed to either bedrest, isolation and confinement, head-down tilt, or space flight. Results indicated that production and release of erythropoietin were decreased following simulated weightlessness and in some space flown subjects. The authors conclude that the responses are much more individual in space than during simulation experiments.     

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.     

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.     

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.     

Persistence of tight junctions and changes in apical structures and protein expression in choroid plexus epithelium of rats after short-term head-down tilt

Major alterations of choroidal cell polarity and protein expression were previously shown to be induced in rats by long-term adaptation to space flight (14 days aboard a space shuttle) or anti-orthostatic suspension (14 and 28 days) performed by tilting rats head-down (i.e. using a ground-based model known to simulate several effects of weightlessness). In rabbits, it was hypothesized that the blood-CSF barrier was opened in choroid plexus, after a short head-down suspension. To understand the early responses to fluid shifts induced by head-down tilts and evaluate the tightness of the choroidal junctions, we have investigated the effects of acute adaptations to anti-orthostatic restraints, using hindlimb-suspended Sprague-Dawley and Wistar rats. Ultrastructural and immunocytochemical studies were performed on choroid plexuses from lateral, third and fourth ventricles, after 30, 90 and 180 minutes of head-down tilt. Alterations were not perceptible at the level of choroidal tight junctions, as shown by freeze-fracture, claudin-1 and ZO-1 immunolocalizations and conventional electron microscopy, after intravenous injection of cytochrome C. The apical surface of choroidal cells was clearly more affected. Microvilli were longer and thinner and ezrin was over-expressed during all the periods of time considered, showing an early cytoskeletal response. Several proteins involved in the choroidal production of cerebrospinal fluid (sodium-potassium ATPase, carbonic anhydrase II, aquaporin 1) appeared first increased (30 minutes after the tilt), and then, returned to the control level or were lowered (after a 3-hour head-down suspension). Although head-down tilts do not seem to damage the blood-cerebrospinal fluid barrier in choroid plexus, it seemed that the expression of several apical proteins is affected very early.     

Estimations of changes in plasma volume during simulated weightlessness

Results of previous investigations on the effects of simulated microgravity (thermoneutral (34.5 degrees C) head-out water immersion, WI) have indicated that plasma volume (PV) increases initially and thereafter decreases to attain values below the pre-immersion level. In these cases, changes in hematocrit (Hct) and hemoglobin concentration (Hgb) were used as indicators of relative changes in PV. In order to test whether changes in Hct and Hgb are accurate measures of changes in PV during simulated microgravity, direct measurements of PV were performed with a modified Evans blue dye dilution technique before, during, and after a 12 h WI experiment. Furthermore, PV was determined with the same technique before, during, and after acute 6 degrees head-down tilt (HDT). Changes in PV were then compared with changes calculated from changes in Hct and Hgb.     

Baroreceptor-mediated suppression of osmotically stimulated vasopressin in normal humans

Increases in central venous pressure and arterial pressure have been reported to have variable effects on normal arginine vasopressin (AVP) levels in healthy humans. To test the hypothesis that baroreceptor suppression of AVP secretion might be more likely if AVP were subjected to a prior osmotic stimulus, we investigated the response of plasma AVP to increased central venous pressure and mean arterial pressure after hypertonic saline in six normal volunteers. Plasma AVP, serum osmolality, heart rate, central venous pressure, mean arterial pressure, and pulse pressure were assessed before and after a 0.06 ml.kg-1.min-1-infusion of 5% saline give over 90 min and then after 10 min of 30 degrees head-down tilt and 10 min of head-down tilt plus lower-body positive pressure. Hypertonic saline increased plasma AVP. After head-down tilt, which did not change heart rate, pulse pressure, or mean arterial pressure but did increase central venous pressure, plasma AVP fell. Heart rate, pulse pressure, and central venous pressure were unchanged from head-down tilt values during lower-body positive pressure, whereas mean arterial pressure increased. Plasma AVP during lower-body positive pressure was not different from that during tilt. Osmolality increased during the saline infusion but was stable throughout the remainder of the study. These data therefore suggest that an osmotically stimulated plasma AVP level can be suppressed by baroreflex activation. Either the low-pressure cardiopulmonary receptors (subjected to a rise in central venous pressure during head-down tilt) or the sinoaortic baroreceptors (subjected to hydrostatic effects during head-down tilt) could have been responsible for the suppression of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).     

Human esophageal pressures and chest wall configuration in upright and head-down posture

Pressures were measured at two levels in the esophagus in 14 young healthy subjects performing slow inspiratory and expiratory vital capacity (VC) maneuvers in upright and head-down posture (180 degrees body tilt). In both postures, a gravitational pressure gradient was found, which increased very slightly with decreasing lung volumes (0.006 cmH2O X % VC-1 X cm descent-1) except for upright expiratory curves above 60% VC. The expiratory pressure gradient tended to be larger in head-down than in upright posture; however, during inspiration the opposite was true. In both postures the pressure change between 100 and 20% VC was smaller in the uppermost zone, which is consistent with the smaller changes in alveolar expansion in this zone. Also, in seven of the subjects, changes in cross-sectional area of the middle and lower part of the rib cage (HRC and LRC) and of the abdomen (ABD) were measured by respiratory inductive plethysmography in upright and head-down posture. The ratio of HRC motion to LRC motion was constant throughout the VC and did not change with posture, yet the ratio of ABD motion to mean RC motion changed with overall volume and was also larger in head-down than in upright posture. In conclusion, the changes in esophageal pressure gradient during slow VC maneuvers in head-down vs. upright posture were not related to (and thus not caused by) changes in chest wall configuration.     

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.     

Acute head-down tilt decreases the postexercise resting threshold for forearm cutaneous vasodilation.

The purpose of this study was to evaluate the role of baroreceptor control on the postexercise threshold for forearm cutaneous vasodilation. On four separate days, six subjects (1 woman) were randomly exposed to 65 degrees head-up tilt and to 15 degrees head-down tilt during a No-Exercise and Exercise treatment protocol. Under each condition, a whole body water-perfused suit was used to regulate mean skin temperature (T(sk)) in the following sequence: 1) cooling until the threshold for vasoconstriction was evident; 2) heating ( approximately 7.0 degrees C/h) until vasodilation occurred; and 3) cooling until esophageal temperature (T(es)) and (T(sk)) returned to baseline values. The Exercise treatment consisted of 15 min of cycling exercise at 70% maximal O(2) uptake, followed by 15 min of recovery in the head-up tilt position. The No-Exercise treatment consisted of 30 min resting in the head-up tilt position. After the treatment protocols, subjects were returned to their pretreatment condition, then cooled and warmed again consecutively. The calculated T(es) threshold for cutaneous vasodilation increased 0.24 degrees C postexercise during head-up tilt (P < 0.05), whereas no difference was measured during head-down tilt. In contrast, sequential measurements without exercise demonstrate a time-dependent decrease for head-up tilt (0.17 degrees C) and no difference for head-down tilt. Pretreatment thresholds were significantly lower during head-down tilt compared with head-up tilt. We have shown that manipulating postexercise venous pooling by means of head-down tilt, in an effort to reverse its impact on baroreceptor unloading, resulted in a relative lowering of the resting postexercise elevation in the T(es) for forearm cutaneous vasodilation.     

Plasma vasopressin, neurophysin, renin and aldosterone during a 4-day head-down bed rest with and without exercise

The purpose of this study was to investigate the main renal and hormonal responses to head-down bed rest, which is currently considered a reliable experimental model for the simulation of weightlessness. Urinary output and electrolytes, plasma renin activity (PRA), aldosterone (PA), antidiuretic hormone (ADH) and immunoreactive neurophysin-I (Np) were measured in eight adult volunteers submitted to a 4-day head-down bed rest (-6 degrees) after a 24-h control period in the horizontal position (day 0). Four of the eight subjects were submitted to two 1-h periods of controlled muscular exercise (50% VO2max) from day 1 to day 4. Throughout the head-down bed rest period, urinary output remained stable, although lower than in the control period (day 0), but the urinary Na/K ratio decreased. Plasma electrolytes and osmolality, and creatinine clearance remained unchanged. There was no significant difference between exercising and non-exercising subjects. At the hormonal level, PRA and PA increased during the head-down bed rest. This increase was more pronounced in the group with exercise. At the end of the tilt period, PRA and PA were about 3 times higher than on day 1. No significant changes could be observed for ADH and Np. It is concluded that a 4-day head-down bed rest results in no apparent changes in neurohypophyseal secretory activity, and in a progressive secondary hyperaldosteronism.     

Scintigraphic evaluation of shape of lung and chest in upright and head-down posture

We determined the configuration of lungs and chest in six healthy young subjects using anteroposterior and lateral technetium-99m-labeled scintigraphic images obtained in upright and in 90 degree head-down posture at 0, 25, 50, 75, and 100% vital capacity (VC). The lung shape was evaluated from curves relating vertical height vs. cumulative volume of 20 apicodiaphragmatic lung zones of equal height. S-shaped curves were obtained, which, after size normalization, were largely independent of volume or posture (P greater than 0.1). However, the apical zones tended to become relatively wider and the diaphragmatic zones relatively smaller with increasing volume, especially between 0 and 25% VC in upright posture and 0-50% VC in head-down posture. Changing posture from upright to head-down also tended to slightly widen the apical zones and to narrow the diaphragmatic zones, which is in line with a greater intrathoracic penetration of the diaphragm/abdomen. The shape of the chest was evaluated from the ratio of the transverse-thoracic and anteroposterior distances over height. These ratios did not clearly change with posture (P greater than or equal to 0.05) but increased by approximately 30% with decreasing volume (P less than 0.01). The fact that these shape changes of the chest were not accompanied by similar changes in lung shape can be explained mainly by widening of the mediastinum when volume decreases. In conclusion, the shape of the lung and chest are similar in head-down and upright humans, in contrast to the reversal of the apicodiaphragmatic differences in alveolar expansion and in transpulmonary pressure.     

Contribution of social isolation, restraint, and hindlimb unloading to changes in hemodynamic parameters and motion activity in rats

The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint), and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient.     

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 in leg vein filling and emptying characteristics and leg volumes during long-term head-down bed rest

Louisy, Francis, Philippe Schroiff, and Antonio Güell.Changes in leg vein filling and emptying characteristics and legvolumes during long-term head-down bed rest. J. Appl.Physiol. 82(6): 1726-1733, 1997.Leg venoushemodynamics [venous distensibility index (VDI), arterial flowindex (AFI), half-emptying time(T_1/2)], and leg volumes(LV) were assessed by mercury strain-gauge plethysmography with venousocclusion and volometry, respectively, in seven men before, during, andafter 42 days of 6° head-down bed rest. Results showed a highincrease in VDI up to day 26 of bedrest (+50% vs. control at day 26,P < 0.05), which tended to subsidethereafter (+20% increase vs. control value at day41, P < 0.05). VDIchanges were associated with parallel changes inT_1/2 (+54% vs. control atday 26 of bed rest,P < 0.05, and +25% vs.control at day 41, P < 0.05) and with a decrease in AFI(49% at day 41 vs. control, P < 0.05). LV continuously decreasedthroughout bed rest (13% vs. control at day41, P < 0.05) but was correlated with VDI only during the first month ofbed rest. These results show that during long-term 6° head-down bedrest alterations of leg venous compliance are associated withimpairment of venous emptying capacities and arterial flow. Changes inskeletal muscle mass and fluid shifts may account for venous changesduring the first month of bed rest but, subsequently, otherphysiological factors, to be determined, may also be involved in legvenous hemodynamic alterations.

     

The dynamic of breathing biomechanics and intrathoracic hemodynamics parameters during microgravity modeling

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.     

Optic Nerve Sheath Diameter Remains Constant during Robot Assisted Laparoscopic Radical Prostatectomy

Background

During robot assisted laparoscopic radical prostatectomy (RALRP), a CO₂ pneumoperitoneum (CO₂PP) is applied and the patient is placed in a head-down position. Intracranial pressure (ICP) is expected to acutely increase under these conditions. A non-invasive method, the optic nerve sheath diameter (ONSD) measurement, may warn us that the mechanism of protective cerebrospinal fluid (CSF) shifts becomes exhausted.

Methods

After obtaining IRB approval and written informed consent, ONSD was measured by ocular ultrasound in 20 ASA I–II patients at various stages of the RALRP procedure: baseline awake, after induction, after applying the CO₂PP, during head-down position, after resuming the supine position, in the postoperative anaesthesia care unit, and on day one postoperatively. Cerebral perfusion pressure (CPP) was calculated as the mean arterial (MAP) minus central venous pressure (CVP).

Results

The ONSD did not change during head-down position, although the CVP increased from 4.2(2.5) mm Hg to 27.6(3.8) mm Hg. The CPP was decreased 70 min after assuming the head-down position until 15 min after resuming the supine position, but remained above 60 mm Hg at all times.

Conclusion

Even though ICP has been documented to increase during CO₂PP and head-down positioning, we did not find any changes in ONSD during head-down position. These results indicate that intracranial blood volume does not increase up to a point that CSF migration as a compensation mechanism becomes exhausted, suggesting any increases in ICP are likely to be small.     

Ten days of head down tilt: effects of isotonic and hypertonic saline loads in normal man

The initial response to bed rest involves an increase in central blood volume leading to a an enhanced renal excretion of fluid and electrolytes. Within 24 hours of head-down bed rest a new steady state condition occurs with a sustained reduction of plasma volume, extracellular fluid volume, total body water, and body weight. It was the purpose of the present study to elucidate the volume homeostatic mechanisms during head-down bed rest by investigating the endocrine and renal responses to a load of sodium chloride given as either an isotonic or a hypertonic solution.