The microgravity environment of space is well tolerated by the cardiovascular system over during periods ranging from weeks to several months. In many ways, the heart, peripheral vasculature, and central cardiovascular control system are exposed to fewer challenges in microgravity than on Earth. Consider the simple act of standing upright in the normal gravity field of Earth. Assumption of an upright posture on Earth causes a redistribution of blood volume to the lower parts of the body, resulting in an increase in blood pressure in dependent blood vessels and a decrease in arterial blood pressure above the level of the heart. The cardiovascular system must quickly compensate for these changes by altering the heart rate, the force of contraction of the heart, and the resistance of the blood vessels to maintain enough blood flow to the brain to prevent loss of consciousness. Under weightless conditions, however, there are no postural changes in blood volume and pressure, which greatly reduces the demands placed on the cardiovascular system to maintain homeostasis. Furthermore, moving about in microgravity requires far less energy than required in gravity, which places less demand on the cardiovascular system.
During the long term, however, many physiological systems become dysfunctional when they are not required to perform at a normal level. For example, the muscles and bones of a leg immobilized in a cast for a month or two become atrophied and weak. Similarly, the relatively unchallenging environment of microgravity ultimately results in dysfunctional changes in the heart, the vasculature, and the central cardiovascular control system that may have harmful consequences during spaceflight and upon reexposure of the human organism to a gravitational field.
For example, many astronauts cannot maintain normal blood pressure and feel dizzy or faint when standing upright immediately following spaceflight, a condition called orthostatic intolerance. This may impair their ability to get out of a spacecraft quickly should an emergency arise, or to perform meaningful work upon arrival in a gravitational field, for example, after a trip to Mars. There are also reports of rhythmic disturbances of the heart (cardiac arrhythmias) during spaceflight and of loss of muscle mass of the heart (cardiac atrophy). The latter two conditions, though less well documented than orthostatic intolerance, represent potentially life-threatening alterations in cardiovascular function. Before examining these problems in more detail, however, we will present a brief review of normal cardiovascular physiology.
Cardiovascular Physiology
The heart is composed of four chambers, the left and right atria and the right and left ventricles. The atria serve as booster pumps to aid in filling the ventricles during their filling cycle—ventricular diastole. The ventricles are the main pumping chambers of the heart. Blood is ejected from the ventricles during their contraction cycle—ventricular systole. The right ventricle pumps blood to the lungs through the pulmonary circulation. The left ventricle pumps blood through the systemic circulation. The systemic circulation is a branching network of vessels. The arteries bring blood to the various tissue beds. Oxygen and nutrients are delivered to the tissues, and carbon dioxide and waste products are removed through the smallest vessels, the capillaries. Capillary blood flows into the venous system starting with the smallest vessels in the venous system, the venules. The smaller veins merge into progressively larger veins ending up in the vena cava which returns blood back to the heart.
From a functional point of view, the large arteries serve as compliant capacitance vessels, ensuring that blood pressure does not fall to zero during ventricular diastole during which no blood is being ejected from the ventricles. The bulk of the resistance to flow in the systemic circulation resides in the micro-circulation, consisting of arterioles, capillaries, and venules. The control of resistance to flow resides in the arterioles which, unlike capillaries and venules, have a muscular wall whose tone can be controlled by local factors (autacoids), by circulating hormones, and by the sympathetic nervous system. The large veins are extremely compliant and serve as a large blood reservoir. These veins have muscular walls whose tone can be increased by sympathetic nervous system stimulation. Constricting the large veins functionally is equivalent to shifting blood from the reservoir into the remainder of the circulation. This is an important function because filling of the right ventricle is determined to a large extent by the pressure in the vena cava—the central venous pressure—which may also be called preload. A drop in central venous pressure can lead to a precipitous drop in the filling of the right ventricle which in turn leads to a drop in cardiac output—the total rate of blood flow out of the heart into the systemic circulation. The large veins also provide small resistance to blood flow.
The cardiovascular system is exquisitely controlled by multiple feedback and control loops. Intrinsic control of the cardiovascular system is achieved by local factors (autacoids) that, for example, control the muscular tone in arterioles to match local blood flow to local tissue demand. Extrinsic control of the cardiovascular system is achieved by the autonomic nervous system and circulating hormones. The autonomic nervous system is composed of two main branches—the parasympathetic nervous system and the sympathetic nervous system. The main function of the parasympathetic nervous system is to slow the heart rate. The sympathetic nervous system has two classes of receptors, alpha and beta. Stimulation of alpha receptors increases venous and arterial tone. Stimulation ofbeta receptors increases the heart rate and the contracting force of the heart (inotropy) and decreases arteriolar tone.
Cardiovascular Alterations Associated with Spaceflight
The constellation of cardiovascular de-conditioning effects associated with spaceflight include decreased orthostatic tolerance (1-8) and exercise capacity (9,10) upon return to a gravitational field, decreased cardiac muscle mass (11), and the occurrence of a variety of arrhythmias in some individuals (12-14). Maintaining exercise capacity and orthostatic tolerance at preflight levels requires the integrity of both cardiac pump function and the multiple neurohumoral control mechanisms that mediate the hemodynamic response to exercise and orthostatic challenge. Orthostatic intolerance is a high priority problem because it may interfere with the crew’s ability to function during reentry and postflight; therefore, we will start our discussion with this problem. In later sections, we will discuss cardiac arrhythmias and cardiac atrophy.
Alterations in Cardiovascular Parameters That May Contribute to the Development of Orthostatic Intolerance. Exposure to microgravity undoubtedly removes the blood pressure gradients from head to feet that are associated with upright posture on Earth (15). Thus, there is an equalization in blood pressures throughout the body. Mean arterial pressure at the feet is reduced from about 200 to about 100 mmHg and is increased within the head from about 70 to about 100 mmHg. Dependent blood vessels are exposed to lower than 1G normal blood pressure, whereas the vessels between the heart and head are exposed to higher than 1G normal blood pressure.
During spaceflight, body fluid shifts from the lower extremities to the thorax, and overall fluid volume is reduced. It is believed that the mechanism of orthostatic hypotension following spaceflight involves pooling of blood in the legs resulting in reduced preload to the heart, a decrease in cardiac output, and low blood pressure (hypotension). About 20% of astronauts after short (weeks) missions and 83% of astronauts after long missions (months) cannot support standing arterial blood pressure for 10 minutes (8). Physiological mechanisms that contribute to orthostatic hypotension include alterations in peripheral vascular resistance, venous compliance, intrinsic vascular reactivity, reduced intravascu-lar volume, altered heart rate arterial baroreflex, and altered cardiac systolic and diastolic function.
Altered Vascular Resistance
Changes in Total Peripheral Resistance (TPR). Fourteen crew members from the Space Life Sciences (SLS)-1 and -2 Space Shuttle flights were studied within 4 hours of landing after flights of 9 or 14 days (3). Hemodynamic measurements were compared between finishers and nonfinishers of a 10-minute stand test. Only nine of the 14 subjects (64%) finished the stand test. There were equally significant postflight increases in upright heart rates and decreases in stroke volumes in both finishers and nonfinishers. The amount of venous pooling was similar in both groups. The critical difference between finishers and non-finishers in this series was inadequate vasoconstrictor response in nonfinishers (29.4 + 2.3 units in finishers vs. 19.9+1.4 units in nonfinishers, p<0.05). Although the vasoconstrictor response increased compared to preflight levels in both subgroups, only the finishers had vasomotor responses enhanced enough to maintain adequate arterial blood pressure. These investigators concluded that microgravity-induced hypovolemia is a likely prerequisite for developing post-flight orthostatic intolerance, but the outcome in a given individual may depend to a great extent on the magnitude of the systemic vasoconstrictor response.
Although the mechanisms that underlie inadequate postflight response remain to be identified, two principal alternatives are (1) adaptation to micro-gravity has caused a degradation of neurohumoral cardiovascular control mechanisms that are essential at 1G, or (2) the dynamic range of the mechanisms that produce appropriate orthostatic vasoconstriction is an inborn characteristic of the individual. A limited range that is adequate for an ordinary 1G condition becomes inadequate in the hypovolemic state early after return from space. A degradation of the neurohumoral vasoconstrictor mechanisms may occur at one or more levels, that is, afferent input, central integration, efferent output, and/or end organ responsiveness. Currently available information provides no conclusive answers (16).
In a study of 24 astronauts before and after missions of 4 to 5 days using two-dimensional echocardiography, the standing TPR index (TPRI) was significantly greater (p < 0.03) in the standing compared with the supine position on all test days except landing day. Similarly, the TPRI orthostatic response decreased on landing day (p<0.03). Thus, there was an apparent reduction in the ability to augment peripheral vascular tone when assuming the standing position (4).
In a study of 40 astronauts before and after spaceflights that lasted up to 16 days, it was found that those who could not complete a 10-minute stand test on landing day had significantly lower (23 + 3 units vs. 34 + 3 units; p = 0.02) standing TPR (7).
Changes in Levels of Catecholamines. Forty astronauts were studied before and after spaceflights of up to 16 days. Of the original 40, seven were excluded because they had consumed promethazine, dextroamphetamine, or caffeine shortly before landing, and four were excluded because blood samples were ruined. On landing day, eight of the remaining 29 astronauts (28%), could not complete a 10-minute stand test due to presyncopal symptoms (dizziness or faintness). It was found that those who did not complete the stand test had significantly reduced peripheral vascular resistance and blood pressure when standing. These same subjects, it was noted, had significantly lower peripheral vascular resistance and supine and standing diastolic and systolic blood pressure before spaceflight. In addition, the nonfinishers had significantly smaller increases in plasma norepinephrine levels when standing than those who finished the stand test (105 + 41 vs. 340 + 62 pg/ml; p = 0.05). These results were taken as evidence for hypoadrenergic responsiveness, possibly centrally mediated, as a contributing factor in postflight orthostatic intolerance (7).
A 2-week head-down bed-rest study (a ground-based model of weightlessness) of eight healthy volunteers demonstrated a decrease in norepinephrine excretion of 35% on day 14 of bed rest from that on the control day. Though excretion rates of norepinephrine decreased, plasma levels were only variably and not significantly decreased. This was likely to be related to concurrent hypovolemia and is still consistent with a subnormal norepinephrine spillover in this setting. Excretion rates of epinephrine, dopamine, and dihydroxyphenyl-acetic acid were unchanged, suggesting that head-down bed rest produces sustained inhibition of sympathoneural release, turnover, and synthesis of norepinephrine without affecting adrenomedullary secretion or renal dopamine production. This sympathoinhibition in the face of decreased blood volume may help to explain orthostatic intolerance in returning astronauts (17).
The discordance between the response of plasma dopamine and plasma norepinephrine documented above may further exacerbate the deleterious effects of the sympathoinhibition. Renal tubular cells can synthesize dopamine from dopa (18), and in normal circumstances, the diuretic, natriuretic, and renal vasodilatory effects of locally produced dopamine are balanced by the effects of renal sympathetic nerve activity and the resultant release of norepinephrine, which promotes renal absorption of sodium and water and reduces dopamine-induced vasodilation (19). It is interesting to note that an extreme example of discordance between plasma dopamine and plasma norepinephrine is found in patients who are deficient in the enzyme dopamine beta-hydroxylase (20). In these patients, excessive production of dopamine, coupled with an inability to convert dopamine to norepinephrine, leads to a volume-depleted state with extraordinarily severe orthostatic hypotension, which is enhanced by the absence of the vasoconstricting properties of norepinephrine.
Other studies have shown a dissociation between an increase in circulating catecholamines and peripheral vasoconstrictor responses, from which it was concluded that there is a blunted vasoconstrictor response to sympathetic stimulation (5,21) following exposure to microgravity. This may be due to downreg-ulation of adrenergic receptors in response to increased levels of plasma norepinephrine in microgravity. During the D2-Spacelab mission, plasma nor-epinephrine in four astronauts was approximately twice the value of that in the supine position on the ground, suggesting that the level of sympathetic nervous activity during microgravity is more similar to the upright ground-based position than to the supine (22).
Changes in Local Mediators. Endothelial functional changes resulting from exposure to microgravity have yet to be extensively studied. As outlined before, some studies document a blunted vasoconstrictor response to sympatho-adrenal activation after spaceflight (5,21), whereas others have shown sym-pathoinhibition (7,17). In either case, it is likely that local endothelial vasodilatory function mediated by endothelium-derived relaxing factor, or nitric oxide, is altered following exposure to microgravity.
Altered Venous Compliance
Central Venous Pressure (CVP). There is some evidence that central venous pressure is decreased during spaceflight. CVP was measured in one subject aboard Space Life Sciences-1 and in two subjects aboard Space Life Sciences-2. Mean CVP in the seated position prelaunch was 8.4 cm water, and with legs elevated, prelaunch in the Shuttle was 15.0 cm water and fell to 2.5 cm water after 10 minutes in microgravity. In these same subjects, however, the left ventricular end-diastolic dimension, as measured by echocardiography, increased within 48 hours in microgravity (23). Given this increase in cardiac filling, it seems likely that a decrease in intrathoracic pressure of greater magnitude than the decrease in CVP may occur in weightlessness, leading to an effective increase in right atrial transmural pressure. Simultaneous measurements of CVP and intraesophageal pressure, recently made in weightless parabolic flight, confirm this hypothesis (24). The SLS-1 and -2 data confirm previous observations in space (25).
Increased Peripheral Pooling of Blood. Data from Skylab-3 and -4 suggest that leg blood flow and compliance increase during the early hours of spaceflight (26), and ground-based studies simulating microgravity have documented an increase in leg vessel compliance (27-29).
Reduced Intravascular Volume
Decreased Red Blood Cell Mass (RBCM). Six astronauts on SLS-1 and -2 were studied. Plasma volume (PV) decreased by 17% within the first day of spaceflight. RBCM decreased as a result of the destruction of red blood cells (RBCs) either newly released or about to be released from the bone marrow, whereas older RBCs survived normally. Upon return to Earth, PV increased, causing a decreased RBC count and increased erythropoietin levels. The proposed mechanism for these changes is that entry into microgravity causes acute plethora secondary to a decreased vascular space, leading to increased hemoglobin, that leads to decreased erythropoietin levels. RBCM decreases to an appropriate level for the microgravity-induced decreased PV via destruction of recently formed RBCs. Acute hypovolemia upon return to Earth stimulates an increase in plasma volume, leading to anemia that stimulates an increase in serum erythropoietin and corrects the anemia (30).
Decreased Plasma Volume (PV). Adaptation to actual and simulated mi-crogravity is associated with decreased total blood volume (2,31). It was initially postulated that diuresis accounts for fluid volume losses during spaceflight; however, diuresis during spaceflight has rarely been documented (32). Body fluid balance was studied on three recent spaceflights (N of subjects = 7) with special emphasis on oral intake and renal excretion of fluid and sodium (33). In no case was increased diuresis and natriuresis observed; rather, both oral fluid and sodium intake, as well as renal fluid and sodium output, appear reduced compared with the preflight condition. These results are consistent with findings during the Skylab program, in which fluid intake and renal fluid loss also appeared reduced or unchanged, at least during the first flight days (34). They are also consistent with the results of SLS-1 and -2 subjects in whom plasma volume, extracellular fluid volume, urine excretion, and fluid intake all decreased, and the glomerular filtration rate (GFR) was elevated (32). It was felt that the reason for the discrepancy between reduced or unaltered renal excretion and reduced body water was most likely due to insufficient caloric intake and subsequent decreased water binding capacity (1 g glycogen binds 3-4 g water; 1 g protein binds 8 g water). In addition, the decreased plasma volume coupled with upper body edema points toward an increased extravasation of fluid as a result of the headward fluid shift (33). Leach et al. postulate that increased permeability of capillary membranes may be the most important mechanism causing spaceflight-induced PV reduction, which is probably maintained by increased GFR and other mechanisms (32).
Hormonal Changes. Following an isotonic saline infusion in microgravity, renal sodium and fluid output were lower than expected from results of simulation experiments; venous plasma norepinephrine and renin were higher. Because plasma arginine vasopressin (AVP) was low, high levels of this peptide were not responsible for decreased renal fluid output during flight (22,35).
SLS-1 and -2 subjects had increased AVP (also referred to as antidiuretic hormone, or ADH) on flight day 1 and on landing day; AVP levels normalized on other days. The elevations on launch and landing days, it was felt, were stress related. Plasma and urinary cortisol levels were elevated, although not statistically significant, throughout the flights, and again, it was felt that stress plays a role in this elevation. Plasma renin activity (PRA) and aldosterone decreased in the first few hours after launch, but PRA was elevated 1 week later. During flight atrial natriuretic peptide concentrations were consistently lower than preflight mean values, (32).
Altered Cardiac Function
Changes in Heart Rate (HR) and the HR Baroreflex. Using a neck collar to produce computer-controlled beat to beat changes in carotid artery transmural pressures in subjects before and after 8 days in orbit in SLS-1 and D2 flights demonstrated a significantly attenuated change in the cardiac cycle length interval for a given change in carotid transmural pressure (36). Similar results were found after head-down bed rest (37). The conclusion of these studies was that spaceflight reduces baseline levels of vagal-cardiac outflow and vagally mediated responses to changes of arterial baroreceptor input. These results were recently corroborated by studies of the spectral power of heart rate and blood pressure in Mir cosmonauts during and after 9 months of spaceflight (38). It has been argued, however (15), that baroreflex assessments based on R-R interval changes alone may be inadequate because they ignore the contribution of stroke volume to cardiac output. For example, HR increases more during in-flight lower body negative pressure (LBNP) than during preflight LBNP, and standing HR is elevated postflight to compensate for the stroke volume deficit imposed by microgravity-induced hypovolemia. These observations alone imply adequate functioning of the cardiac baroreflex arm.
A study of 24 astronauts following missions from 4 to 5 days found that, on landing day, supine HR increased by 23% (p < 0.0005) and standing HR increased by 35% (p< 0.0001), compared with preflight values. Preflight HR began to level off 2 or 3 minutes following the initial increase when standing, but postflight, it continued to increase for the duration of the 5-minute stand test. This was taken as evidence of postflight orthostatic dysfunction (4,6).
Changes in Ventricular Filling and Cardiac Contractility. After Apollo flights, standard anterior-posterior chest roentgenograms taken pre- and post-flight showed that heart size decreased following spaceflight (39). These results have been confirmed in a study of 24 astronauts after missions of 4 to 5 days evaluated by two-dimensional echocardiography. Supine left ventricular end di-astolic volume index (EDVI) diminished by 11% (p<0.04) on landing day, compared with preflight. Supine left ventricular stroke volume index (SVI)diminished by 17% (p<0.006) on landing day, compared with preflight. Both recovered to preflight levels within 48 hours. Standing EDVI was less than that of supine EDVI, but SVI did not change significantly with position. The ejection fraction and the velocity of circumferential fiber shortening did not change significantly, suggesting no effect on myocardial contractility (4).
More recent early in-flight echocardiographic measurements in three subjects from SLS-1 and -2 showed an increase in cardiac filling, the mean increase in the left ventricular (LV) diastolic diameter was from 4.6 cm to 4.97 cm (23). Analyzing the data by a technique that produces a three-dimensional reconstruction of the LV showed a time course of adaptation where the initial increase in LV size was followed within 48 hours by a significant decrease in size relative to preflight supine dimensions (16). Contractile state—as defined by the LV ejection fraction, end systolic volume, and velocity of circumferential fiber shortening—did not change during the mission. Stroke volume measurements after 2 days in space approximated the 1 G supine data, and measurements after 5 days or later approached, but did not reach, preflight upright levels. This suggests that cardiovascular conditions in microgravity after adaptation may represent an intermediate hemodynamic state that accurately reflects the normal 24-hour human postural pattern, that is, one 8 hour part supine and two parts upright (16,23).
A recent bed-rest study suggests that changes in LV pressure-volume characteristics may develop during a 2-week period of bed rest in normal subjects and produce a stiffer ventricle that has reduced end-diastolic volume, compared to the normal physiological range of filling pressures (9).
Alterations in Cardiac Muscle Mass. Magnetic resonance imaging of four members of the German D-2 German Spacelab mission showed a significant loss of myocardial mass after a 10-day mission (11). Levine et al. (40) found that normal subjects subjected to 2 weeks of microgravity simulated by bed rest showed a significant reduction in ventricular mass also, as measured by magnetic resonance imaging. However, the mechanisms by which reduction in cardiac mass occurs, the functional sequelae of the changes in cardiac mass, and whether or not these changes are reversible after space flight all remain to be investigated. Alterations in Cardiac Electrical Function. Another aspect of the cardiovascular deconditioning process involves potential alterations of cardiac conduction processes associated with spaceflight. Cardiovascular deconditioning has been investigated quite extensively, but there have been relatively fewer systematic investigations into the effects of spaceflight on cardiac electrical function. However, a variety of heart rhythm disturbances have been observed in astronauts during and after spaceflight. Occasional premature ventricular contractions were seen in Gemini and Apollo missions (13,41). Reports indicate that all crew members in the Skylab series had some form of rhythmic disturbance (14,41) and one individual experienced a five-beat run of ventricular tachycardia. The incidence of arrhythmias was higher during flight than during preflight testing and higher than would be expected in a random sampling of a healthy population. Cardiac arrhythmias have also been seen during Shuttle flights (41) and on Mir. Analysis of nine 24-hour ECG recordings (Holter monitoring) obtained during long-term spaceflight on Mir revealed one 14-beat run of ventricular tachycardia (12). Two Mir missions have undergone major changes in crew composition and/or responsibilities due to cardiac dysrhythmias (42). Furthermore, a research primate recently died suddenly shortly after returning to Earth from extended space flight; cardiac dysrhythmic mechanisms were suspected as a possible cause (43).
Thus, there seems to be significant anecdotal evidence suggesting that spaceflight is associated with an increased susceptibility to potentially life-threatening ventricular arrhythmias. Furthermore, it is likely that ventricular arrhythmias during spaceflight will be of increasing concern in the future as older individuals are involved in spaceflight and as the durations of missions lengthen. At a joint National Aeronautics and Space Administration/National Space Biomedical Research Institute workshop in January 1998, cardiac arrhythmias were identified as the leading cardiovascular risk to a human Mars exploration mission (44). Older individuals have a greater statistical likelihood of having underlying structural heart disease, in particular, coronary artery disease and thus, will be at greater risk for heart rhythm disturbances. If spaceflight does increase susceptibility to ventricular arrhythmias, such arrhythmias could pose a significant threat to crew safety and mission success. However, the available data are too anecdotal to permit one to conclude whether spaceflight does increase susceptibility to ventricular arrhythmias. Therefore, it is important to conduct systematic investigations to determine whether exposure to microgravity alters cardiac electrical stability.
Recently a new technique—the measurement of microvolt level T wave alternans (TWA)—has been developed. In a series of clinical studies in varied patient populations, this technique compared favorably to other noninvasive risk stratifiers and invasive electrophysiological testing as a predictor of sudden cardiac death, ventricular tachycardia, and ventricular fibrillation (45-47). In a recent National Space Biomedical Research Institute project, healthy volunteers participated in a 16-day head-down, tilt, bed-rest study (a ground-based analog of weightlessness) and had TWA measured before and after the bed-rest period during bicycle exercise stress. In three subjects, bed rest induced sustained TWA, although they had an onset heart rate above the 110 beat per minute (bpm) cutoff below which TWA is clinically associated with increased arrhythmic risk. In these subjects, sustained TWA disappeared 2 to 3 days after bed rest. In one subject who had sustained TWA and an onset heart rate above 110 bpm before bed rest, bed rest abolished sustained TWA, which reappeared 3 days after bed rest. These findings provide the first evidence that simulated weightlessness has a measurable effect on myocardial repolarization processes, which suggests that spaceflight may alter susceptibility to life-threatening ventricular arrhythmias (48).
The potential lethal arrhythmic risk for astronauts is sustained ventricular tachycardia or ventricular fibrillation. Nonsustained ventricular tachycardia could cause syncope. Given the data suggesting that cardiac arrhythmias might pose a problem for long-term spaceflight and given that the consequence of ventricular arrhythmias may be astronaut death, this will be an important area of further study.
Countermeasures
Fully effective countermeasures against the problem of orthostatic intolerance have yet to be developed. Currently, the US space program regularly employs anti-g suits for reentry to limit acutely the amount of blood pooling in the lower extremity and oral intake of saline before reentry in an attempt to restore intravascular volume closer to preflight levels. Oral saline loading appears to be effective in preserving standing arterial blood pressure after short flights of up to 5 days (49); however, it has not been as effective after longer flights. This finding is consistent with other evidence that changes in autonomic control of cardiovascular function, and perhaps myocardial contractile function, rather than simply inadequate intravascular volume, is responsible for orthostatic intolerance following spaceflight.
One technique that appeared promising in the past was the use of lower body negative pressure (LBNP) during flight to simulate exposure periodically to gravity gradients. The LBNP device is a cylinder into which the subject’s lower body is placed, and it has a rubber cuff that goes around the waist. A partial vacuum created in the cylinder causes blood to pool in the legs, similar to standing in Earth’s gravity. Although exposure to LBNP during flight was moderately protective against orthostatic intolerance upon return to Earth, it was unpopular with astronauts, who reported that exposure to LBNP during flight caused them to reexperience many of the unpleasant sensations they had experienced upon initial exposure to weightlessness (50), such as nasal stuffiness and facial fullness. This is consistent with the idea that the cardiovascular system makes appropriate adaptations to weightlessness and that trying to simulate gravitational conditions periodically during flight may interfere with these appropriate in flight adaptations.
A new pharmacological countermeasure, midodrine, was recently tested and found protective against orthostatic intolerance following microgravitational simulation for 16 days (51). There is evidence that both venous return and peripheral vascular resistance are reduced after spaceflight. Though not the only contributors, both of these factors most certainly increase the incidence of post-spaceflight orthostatic hypotension and presyncope. Several studies have demonstrated a reduction in cardiac stroke volume upon return from space (3,4,7), and others have shown reduced resistance responses to standing, particularly in those astronauts who have the most difficulty maintaining arterial blood pressure while standing (3,7). Midodrine is an agonist at a-adrenergic receptors located on the smooth muscle in both veins and arterioles, and thus reduces venous pooling and increases peripheral vascular resistance (52-54) by reducing the diameters of arterioles and veins. The success of this trial after bed rest (51) suggests that midodrine also may be an effective treatment for orthostatic hypotension following spaceflight. Trials of midodrine following spaceflight are now being conducted.
Conclusion
The cardiovascular system performs fairly well during spaceflight. The primary adverse effects of spaceflight on the cardiovascular system are orthostatic intolerance, cardiac arrhythmias, and cardiac atrophy. Spaceflight also impairs exercise intolerance, but current in-flight exercise programs seem to be an adequate countermeasure. Preexisting silent cardiovascular disease (such as coronary artery disease) may also become manifest during long-duration spaceflight, particularly in older astronauts.
In terms of the primary adverse effects, postflight orthostatic intolerance is a current operational problem that occurs at high frequency, particularly after long-duration spaceflight. Orthostatic intolerance is generally not life-threatening. The task here is to develop and test effective countermeasures.
It is not known whether or not spaceflight increases the risk of life-threatening cardiac arrhythmias. However, if it does, the consequences could be the death of an astronaut. The task here is to establish whether or not spaceflight increases susceptibility of the heart to life-threatening arrhythmias and if so, to develop effective countermeasures.
Finally, it appears that short-duration spaceflight may modestly decrease cardiac mass. It is not known whether the degree of cardiac atrophy increases with the duration of spaceflight, what are the mechanisms involved, what are the functional sequelae, and whether this effect is reversible after spaceflight. The task here is to answer these questions and if indicated, develop effective countermeasures.
