Space travel imposes significant stress on the body’s systems used to adapt to the environment. In a bed-rest study simulating weightlessness, Dr. Gordon H. Williams is studying the effects on the adaptive mechanisms of menstruating women and men over age 50, two well-represented groups among current and future space travelers. He will examine modifications to the function of the heart, vascular system and kidney, which will lead to a better understanding and treatment for common cardiovascular diseases on Earth.
Overview
Influence of Gender and Age on Renal and Cardio-Endocrine Responses to Simulated Microgravity
Principal Investigator:
Gordon H. Williams, M.D.
Organization:
Harvard - Brigham and Women's Hospital
Technical Summary
Orthostatic intolerance remains an operational problem following space flight, and has been observed to be more pronounced among women than among men. In addition, there is growing evidence that cardiac dysrhythmias may pose a threat to the health of space travelers.
In our previous studies we observed that subjects on a constant high dietary sodium intake during simulated weightlessness have varying degrees of sodium balance response. Furthermore, the variability in response correlated with orthostatic tolerance and subjects age. The overall goal of this study is to assess in women (a population at increased risk for orthostatic intolerance) and in men over the age of 50 (an age range more consistent to that of astronauts than the <35 year olds involved in our previous studies) the impact of simulated microgravity on volume-regulating systems. A secondary objective is to search for any correlation between changes in these systems and changes in myocardial electrical stability. A final goal is to determine the effect of two potential countermeasures: midodrine in women and low-dose spironolactone in older men.
This work has implications for the treatment and prevention of maladaptive hemodynamic responses experienced by astronauts in flight and on return to Earth. It will increase our understanding of the mechanisms by which weightlessness changes volume and sodium homeostasis, and possibly cardiac electrical stability, thereby, providing entree to develop appropriate countermeasures. Perhaps most importantly, it will broaden our database to include older individuals and women, two groups who are well represented among our population of current and future space travelers. Finally, the results of these studies may further our understanding of the pathophysiology of alterations in volume homeostatic mechanisms in cardiovascular diseases such as congestive heart failure.
Specific Aims:
- To investigate the influence of age on the pattern of renal sodium handling and the acute responsiveness of the RAAS following simulated microgravity exposure
- To investigate the influence of gender on the pattern of renal sodium handling and the acute responsiveness of the RAAS following simulated microgravity exposure
- To investigate the effects of the alpha-1 agonist midodrine, as a countermeasure against orthostatic intolerance following microgravity exposure in women
- To investigate the effects of spironolactone in older men on the renal-endocrine responses to simulated microgravity, and on changes in myocardial electrical stability resulting from microgravity exposure
Main Findings:
The data we have compiled thus far has shown that individual predisposition plays a very important role in orthostatic intolerance. We found that several baseline physiological characteristics are associated with an increased susceptibility to orthostatic intolerance. These characteristics include, but are not limited to, the renin-angiotensin-aldosterone system, the autonomic system, and leg venous compliance. These findings helps us in answering CQ 3.08 by identifying the critical characteristics that contributes to orthostatic intolerance enabling us to create a new model for the role of predisposition in orthostatic intolerance.
Unique Claims of Study:
Individual predisposition plays a critical role in the development of orthostatic intolerance.
Earth Applications
The results of this study may further our understanding of the pathophysiology of alterations in volume homeostatic mechanisms in cardiovascular diseases such as congestive heart failure.
This project's funding ended in 2004