Cardiovascular adaptations to spaceflight are a normal physiological response to the elimination of the most basic physical force acting upon the body, gravity. Study of these adaptations can be directed toward two purposes. First, is amelioration of the adaptation in order to reduce the risk to the astronauts and equipment. This is our primary mission in the Cardiovascular Laboratory at Johnson Space Center. However, a second, more global, purpose is to use the adaptation as a vehicle to better understand basic physiology and pathophysiology. Efforts towards these two ends can be symbiotic. As spaceflight data have accumulated, and I have collaborated with practicing clinicians, I have come to appreciate the importance of the second purpose. My collaborations have brought me to the group of Dr. Arthur C. Guyton at the University of Mississippi Medical School, who were very interested in incorporating spaceflight cardiovascular data into the famous Guyton models of cardiovascular function. Changes have been made to the equations as a result of the spaceflight data.

During upright posture, large hydrostatic gradients develop due to gravity. This is well understood and easily studied. However, pressure gradients also exist during supine posture. There is a pressure gradient along the vena cavae from the weights (due to gravity) of organs and tissues. These pressures influence the control of cardiac output. This phenomenon is not well understood and is not easily studied on Earth, because it is impossible to eliminate gravity on Earth. Microgravity is the only environment in which the importance of these influences can be studied. Dr's Guyton, Coleman and Summers have given me the following quote: "Spaceflight is the single platform on which the effects of gravity on cardiovascular function can be dissected out. Incorporation of Dr. Meck's spaceflight data into our models of cardiovascular function has had two major effects: correction of our venous return curves by the addition of the effects of weights of organs and tissues on pressures along the vena cavae and resistance to venous return; and appreciation of the effects of differences in the relative centers of gravity between genders on vascular capacitance, mean circulatory filling pressures and venous return. These findings have tremendous clinical importance". The findings may relate to management of several disease states, such as: obesity related congestive heart failure; hypertension; ascites; renal and cardiovascular derangements due to liver failure; shock after abdominal trauma; and dehydration and syncope. It could also help to optimize clinical techniques such as laproscopic surgery, peritoneal dialysis and colonoscopy.
There are three main cardiovascular effects of spaceflight on which we work in the Cardiovascular Laboratory at Johnson Space Center that have clinical significance: development of autonomic dysfunction; changes in cardiac function; and greater susceptibility to postflight orthostatic hypotension in women than in men.

Autonomic Dysfunction
Elimination of gravity appears to provoke disruption of autonomic control of the circulation. This manifests as: decreased orthostatic tolerance; decreased baroreflex function; decreased sympathetic responsiveness to orthostatic stress; and possible dysregulation of baroreceptor afferent input. However, recovery from these symptoms occurs spontaneously over time. The pattern of arterial pressure responses to upright posture in presyncopal subjects on landing day resembles those of autonomic dysfunction. On landing day, in presyncopal subjects, norepinephrine release is significantly smaller than that in astronauts who do not become presyncopal. However, their release of both epinephrine and arginine vasopressin are significantly greater than preflight, and also significantly greater than that of non-presyncopal astronauts. Thus, it appears that there may be a microgravity-related difference in central processing and integration of baroreceptor afferent input. There are several aspects of this research that may have clinical implications. First, it is the only environment in which the effect of the force of gravity on normal autonomic control of the circulation may be studied. Second, it is a model of autonomic dysfunction due to disuse atrophy, and of the response of the central nervous system to lack of baroreceptor input. Third, it is a model of recovery from autonomic dysfunction.

Cardiac Function
We also have documented changes in cardiac function as a result of long-duration, but not short-duration, spaceflight. We have noted changes in atrio-ventricular conduction time (increased P-R interval); prolonged ventricular repolarization (increased Q-Tc interval) and inhomogeneity of ventricular repolarization (increased Q-T dispersion). We also have noted reduced ejection fractions and evidence of diastolic dysfunction. Perhaps most importantly, there have been increased ventricular dysrhythmias, with at least one reported episode of ventricular tachycardia during flight. Similar to the autonomic dysfunction, these effects recover spontaneously with time. These findings also may have important clinical implications. While cardiac loading is easy to study on Earth, cardiac unloading is not. Microgravity offers a unique perspective into the effects of prolonged unloading on venous return, control of cardiac output, systolic and diastolic function and genesis of cardiac dysrhythmias. In summary, these data provide greater insight into the effects of basic physical forces on cardiac function.

Gender
Females are much more susceptible to postflight orthostatic hypotension than are males. They have a five-fold greater incidence of presyncope during postflight stand/tilt tests than do men. They also have a three-fold greater loss of plasma volume, and a greater dependence on plasma volume to maintain standing stroke volumes. In addition, they have a greater loss of sympathetic responsiveness on landing day than either presyncopal or non-presyncopal men. When these data were entered into the Guyton models, it was found that the 18% lower center of gravity in women could explain the greater loss of plasma volume. Because of this, the model predicts that, upon transfer to the microgravity environment, the amount of fluid shifting headward is greater in women: thus the reflex- mediated compensatory diuresis is greater. This spaceflight finding has clinical significance for the importance of baseline hydration status on vascular capacitance and venous return, and on differences in cardiovascular disease processes between men and women.

Conclusion
In conclusion, microgravity offers a unique research laboratory. Data collected in this microgravity laboratory have demonstrated the importance of the basic physical force of gravity on cardiovascular function. These determinations cannot be reproduced on Earth. This research has important clinical implications regarding basic cardiovascular physiology and pathophysiology.

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