Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we applied a powerful, new method cardiovascular system identification (CSI) for the study of the effects of space flight on the cardiovascular system in order to develop effective countermeasures.
CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms.
We applied CSI in conjunction with the bed rest protocol of the Human Studies Core project. This protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors upright tilt, standing and bicycle exercise to provide orthostatic and exercise challenges. We found that a number of autonomically mediated responses, in particular the heart rate baroreflex, were diminished as a result of head down tilt bed rest.
Based on review of our preliminary human data, as well as based on animal data and computer simulation data obtained by other investigators in the NSBRI Cardiovascular Alterations Team, we decided to test a pharmacologic countermeasure which is applied at the very end of the bed rest period. This countermeasure was applied using the same bed rest protocol used to obtain the control data. This double blinded prospective evaluation of the countermeasure demonstrated that it was successful in diminishing orthostatic intolerance.
This project has led to better understanding of the mechanisms of orthostatic intolerance and the identification of a potential pharmacologic countermeasure. The CSI methodology used in this study can be also applied to the study of patients with a range of diseases that alter closed loop cardiovascular regulation such as heart failure, diabetes, and hypertension and may also be used to monitor treatment of these patients.