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Body fluid regulation is affected by gravity. The primary mechanisms of the etiology of hypovolemia found in simulation studies on earth and after space flight are different. The increased diuresis after increase of central blood volume postulated by Henry Gauer could not be found. Based on recent findings, new hypotheses about fluid volume regulation during space flight have emerged. The reduced blood volume in space is the result of 1) a negative balance of decreased fluid intake and smaller reduction of urine output; 2) fast fluid shifts from the intravascular to interstitial space as the result of lower transmural pressure after reduced compression of all tissue by gravitational forces especially of the thorax cage; and 3) fluid shifts from intravascular to muscle interstitial space because of less muscle tone required to maintain body posture. Additionally, loss of erythrocytes reduces blood volume. The attenuated diuresis during space flight can be explained by increased retention after stress-mediated sympathetic activation during initial phase of space flight, stimulation caused by reduced red cell mass, and activation after fast blood volume contraction. Additionally, the relation between plasma osmolarity and vasopressin release might be disturbed in microgravity.
Impaired autonomic control represents a cardiovascular risk factor during long-term spaceflight. Little has been reported on blood pressure (BP), heart rate (HR), and heart rate variability (HRV) during and after prolonged spaceflight. We tested the hypothesis that cardiovascular control remains stable during prolonged spaceflight. Electrocardiography, photoplethysmography, and respiratory frequency (RF) were assessed in eight male cosmonauts (age 41-50 yr, body-mass index of 22-28 kg/m2) during long-term missions (flight lengths of 162-196 days). Recordings were made 60 and 30 days before the flight, every 4 wk during flight, and on days 3 and 6 postflight during spontaneous and controlled respiration. Orthostatic testing was performed pre- and postflight. RF and BP decreased during spaceflight (P < 0.05). Mean HR and HRV in the low- and high-frequency bands did not change during spaceflight. However, the individual responses were different and correlated with preflight values. Pulse-wave transit time decreased during spaceflight (P < 0.05). HRV reached during controlled respiration (6 breaths/min) decreased in six and increased in one cosmonaut during flight. The most pronounced changes in HR, BP, and HRV occurred after landing. The decreases in BP and RF combined with stable HR and HRV during flight suggest functional adaptation rather than pathological changes. Pulse-wave transit time shortening in our study is surprising and may reflect cardiac output redistribution in space. The decrease in HRV during controlled respiration (6 breaths/min) indicates reduced parasympathetic reserve, which may contribute to postflight disturbances.
Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased significantly (P < 0.05) by 26, 23 and 27% after 1 and 2 weeks in space and on landing day, respectively, compared with preflight values, which is also consistent with improved autoregulation. We conclude that human cerebral autoregulation is preserved, and possibly even improved, by short-duration spaceflight.
Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith-ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith-ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith-sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.
c2005 Elsevier Ltd. All rights reserved.
When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38-44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445% during 30 mmHg straining on earth and 792% in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.
Orthostatic intolerance (OI) is common after space flight and resembles the disabling idiopathic orthostatic intolerance commonly observed in otherwise healthy young individuals. OI can arise from reduced sympathetic nervous system activity and, paradoxically, also from increased sympathetic nervous system activity. Patients with early manifestations of pure autonomic failure demonstrate an etiology based upon reduced sympathetic nervous system activity. Patients with hyperadrenergia demonstrate an etiology based on increased sympathetic nervous activity. For many years, we have recognized that the microgravity environment induces adaptation in the cardiovascular system and its autonomic control mechanisms that lead to the presence of OI on return to gravity. Understanding the nature of OI in astronauts returning from space as well as in the relevant patient population on earth has been a priority of Vanderbilt's Center for Space Physiology and Medicine in recent years. A major purpose of the autonomic experiment in the Neurolab mission was to identify whether the OI experienced by astronauts on return to earth was best explained by a hypoadrenergic or hyperadrenergic state. To address this question, we analyzed sympathetic nervous system activity inflight by 1) measurement of plasma catecholamines; 2) assessment of peroneal microneurographic sympathetic nerve traffic; and 3) assessment of norepinephrine spillover and clearance during infusion of tritiated norepinephrine. These studies documented a slight (five bursts per minute) increase in muscle sympathetic nerve activity, a 200 pg/ml increase in plasma norepinephrine level, and a 350 ng/min increase in norepinephrine clearance. Plasma norepinephrine and norepinephrine spillover and clearance were also raised on recovery day. These data indicate that enhanced sympathetic activation, rather than reduced sympathetic activation, accompanies the orthostatic intolerance following microgravity.
We hypothesize that reduced sympathetic stimulation of erythropoietin production may maintain the anemia which develops in virtually all space travellers. We tested this hypothesis in a human model of reduced sympathetic activity. Thirty-three patients with the Bradbury-Eggleston syndrome were divided into three groups according to their hemoglobin (Hgb) level. Patients with low Hgb had lower upright norepinephrine and lower upright renin. Patients with anemia also had inappropriately low plasma erythropoietin levels. We administered recombinant erythropoietin (Epogen) 25-50 units/kg s.c. 3 times per week and found that the anemia seen in autonomic failure could be reversed by this treatment. These results support the hypothesis that erythropoiesis is modulated by the sympathetic nervous system and that at such mechanisms may also operate in the microgravity environment where sympathetic activity is reduced.
Increased sensitivity of end-organ responses to neuroendocrine stimuli as a result of prolonged exposure to the relative inactivity of microgravity has recently been hypothesized. This notion is based on the inverse relationship between circulating norepinephrine and beta-adrenoreceptor sensitivity. Beta-adrenoreceptor activity is reduced in individuals who have elevated plasma norepinephrine as as a result of regular exposure to upright posture and physical exercise. In contrast, adrenoreceptor hypersensitivity has been reported in patients with dysautonomias in which circulating catecholamines are absent or reduced. Taken together, these studies and the observation that circulating plasma norepinephrine has been reduced during spaceflight and in groundbased simulations of microgravity prompt the suggestion that adrenoreceptor hypersensitivity may be a consequence of the adaptation to spaceflight. We conducted an experiment designed to measure cardiovascular responses to adrenoreceptor agonists in human subjects before and after prolonged exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that adaptation to microgravity increases adrenoreceptor responsiveness, and that this adaptation is associated with reduced levels of circulating norepinephrine.
Microgravity is known to stress the heart and blood vessels and to perturb the normal neural regulation of the cardiovascular system. In an effort to gain greater insight into the adjustments of neural control of the cardiovascular system in space, we have used a model of simulated microgravity, the -6 degrees head-down tilt body position (HDT). As a common method for the description of the functional state of the cardiovascular system the power spectral analysis of the heart rate can be used. The following working hypotheses were postulated: 1. HDT causes an acute activation of the parasympathetic nerve traffic to the heart, which is detectable by a reduction in heart rate and by the spectral power distribution of the heart rate variability. 2. HDT induces changes in the autonomic nervous response to upright posture which can be detected after a 45-minute period of head-down tilt.
Post-flight orthostatic intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of orthostatic intolerance.