Space travel imposes significant stress on the body’s systems used to adapt to the environment. In bed rest studies, Dr. Gordon H. Williams is investigating the influence of various countermeasures on renal and endocrine responses to orthostatic stress, in reducing cardiac electrical instability, and on orthostatic tolerance. Examining these modifications to the function of the heart, vascular system and kidney will lead to better understanding and treatment for common cardiovascular diseases on Earth.
Overview
Effects of Microgravity on Renal, Endocrine and Volume-Regulatory Function
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. In addition, there is growing evidence that cardiac dysrhythmias may pose a threat to the health of space travelers. At present, no effective countermeasures exist for orthostatic intolerance and for the probable increased risk of ventricular dysrhythmias.
In the last six years, we have addressed the subject of renal, endocrine and volume-regulating function during head-down tilt bed rest. We have found that simulated microgravity induces changes in the volume-regulating systems and electrolyte excretion, and leads to changes in cardiac electrical stability. We have also found that using our tilt-test protocol, the pre-bed rest tilt-test tolerance was predictive of post-bed rest tilt-test tolerance.
We propose now to conduct three double-blinded randomized trials to:
- Investigate the use of a pre-bed rest tilt-test as a means to screen countermeasures against orthostatic intolerance, and investigate the influence of these countermeasures on the renal and endocrine responses to orthostatic stress.
- Develop effective interventions for the treatment of orthostatic intolerance in women since from our previous studies this complication of space travel appear to have a gender difference.
- Investigate the effectiveness of individualized countermeasures identified during a pre-bed rest tilt-test in reducing post-bed rest orthostatic intolerance, as well as their influence on the renal and endocrine responses to orthostatic stress.
- Investigate the effects of different countermeasures in reducing cardiac electrical instability, and to study the effects of these countermeasures on baseline orthostatic tolerance.
- Investigate the effects of different countermeasures in reducing cardiac electrical instability after simulated microgravity, and to study the effects of these countermeasures on orthostatic tolerance and on the renal and endocrine responses to simulated microgravity. This project interacts closely with a companion project: Effects of Microgravity on Cardiovascular Function, with Richard Cohen, M.D., Ph.D., principal investigator.
Earth Applications
Orthostatic hypotension is an increasing medical problem. In some cases, it is related to medications or disease. Often however, it is related to structural changes in the individual's life, e.g., prolonged bed rest from an operation, injury or disease, and/or termed idiopathic. The latter condition affects nearly one million individuals in the United States and is more common in women of reproductive age. The current research will provide information concerning the relation of hormonal changes to the development of and background for orthostatic hypotension, thereby providing entre to specific treatment and preventive strategies.
This work also has implications for the treatment and prevention of maladaptive hemodynamic responses to volume expansion and upright posture experienced in a variety of cardiovascular diseases such as congestive heart failure. Of interest, both of these conditions are more common and more severe in women than men. Our findings of gender differences in renal, hormonal and cardiovascular responses to simulated microgravity and upright tilt tolerance may provide a mechanistic explanation for these differences and allow the development of more specific, individualized preventative and treatment programs.
This project's funding ended in 2006