Alterations in Cardiovascular Regulation and Function During Long-Term Simulated Microgravity (Synergy Project with Musculoskeletal Alterations Team)
Richard J. Cohen, M.D., Ph.D.
Harvard Medical School/MIT
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 addition, numerous reports from the past 30 years suggest that the incidence of ventricular arrhythmias among astronauts is increased during spaceflight. However, the effects of spaceflight and the associated physiologic stresses on cardiac conduction processes are not known, and an increase in cardiac susceptibility to arrhythmias has never been quantified.
In this project, we are applying the most powerful technologies available to determine, in a ground-based study of long duration spaceflight, the mechanisms by which spaceflight affects cardiovascular function, and then on the basis of an understanding of these mechanisms to develop rational and specific countermeasures. To this end we are conducting a collaborative project with the Musculoskeletal Alterations Team. The team is conducting bed-rest studies in human subjects lasting 17 weeks, which provides a unique opportunity to study the effects of long-duration microgravity exposure on the human cardiovascular system. We are applying a number of powerful new methods to these long term bed rest subjects, including cardiovascular system identification (CSI), microvolt level T-wave alternans analysis, and cardiac magnetic resonance imaging to assess non-invasively the effects of simulated long-duration spaceflight on the cardiovascular system.
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 as well as other important physiologic mechanisms. With an additional non-invasive measurement of stroke volume (SV ultrasound Doppler method), the model may be extended to also include the characterization of the peripheral resistance baroreflex which may play a central role in the development of orthostatic intolerance and measures of systolic and diastolic function.
To determine whether simulated long-term space flight increases the risk of developing life-threatening heart rhythm disturbances such as sustained ventricular tachycardia (defined as ventricular tachycardia lasting at least 30 seconds or resulting in hemodynamic collapse) and ventricular fibrillation, we are applying a powerful new non-invasive technology for the quantitative assessment of the risk of life-threatening ventricular arrhythmias. This technology involves the measurement of microvolt levels of T-wave alternans during exercise stress. In addition, we are obtaining 24-hour Holter monitoring to detect non-sustained ventricular tachycardia and to assess heart rate variability. Finally, in order to investigate the effect of long-duration microgravity on cardiac mass, cardiac magnetic resonance images are being obtained before and after the bed-rest period.
To date, measurements for CSI, 24-hour Holter monitoring, and cardiac magnetic resonance imaging have been made on seven long-term bed rest subjects. Measurements for TWA analysis have been made in four of these subjects.