Overview

Cardiovascular Effects of Simulated Microgravity in Man

Principal Investigator:
Richard J. Cohen, M.D., Ph.D.

Organization:
Massachusetts Institute of Technology
Harvard-MIT Division of Health Sciences and Technology

NASA Taskbook Entry

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Technical Summary

This project is targeted towards studying and developing countermeasures to two of the Cardiovascular Critical Risks:

1. Development of post-flight orthostatic intolerance
2. Increased susceptibility to ventricular dysrhythmias.

The development of orthostatic intolerance is a well known adverse effect of space flight on the cardiovascular system, and is a current operational problem for NASA. Astronauts post-flight may experience a drop in arterial pressure upon adopting the upright posture after flight, which may be sufficiently severe to cause presyncope or syncope. This effect is greater the longer the duration of the flight, and is more pronounced in women than in men. During space flight intravascular volume is decreased and cardiovascular reflexes are down-regulated because the cardiovascular system is no longer subjected to the stresses associated with changes in posture. Upon return to a gravitational environment, blood pools in the large veins of the lower extremities and the splanchnic circulation, leading to a drop in preload to the heart leading to a decrease in cardiac output. In addition, the reflex ability to increase heart rate and constrict arteries and veins is diminished, and there are also changes in cardiac systolic and diastolic function. Countermeasures of salt and water loading prior to re-entry and the use of G-suits are not adequate countermeasures to prevent the development of orthostatic intolerance, particularly after long duration flights. Our goal with respect to this cardiovascular risk is to better understand the detailed mechanisms leading to orthostatic intolerance and to develop and test mechanism-based countermeasures.

There have been several anecdotal reports of documented episodes of self-terminating ventricular tachycardia during space flight14. In addition it has been reported that Russian cosmonauts have suffered from ventricular arrhythmias, and two primates have suffered cardiovascular collapse after return from space flight (without ECG documentation). These data suggest that space flight may be conducive to the development of ventricular arrhythmias. However, it is not known whether or not this is in fact the case. If long duration space flight does increase the risk of potentially lethal ventricular arrhythmias then this would obviously pose an enormous problem for very long duration flights. Our goal in this project is to determine in controlled ground-based experiments, whether there is evidence that simulated micro-gravity in fact alters cardiac electrical activity in a manner that may increase susceptibility to ventricular arrhythmias. If we find evidence that this is in fact the case, then we will attempt to establish mechanism and identify potential countermeasures.

In this project we analyze data from ground-based human studies in which 16 day head down tilt bed rest is used to simulate microgravity. We will be studying the following groups in order to examine the effects of gender and age on these cardiovascular risks.

1. men under age 50
2. premenopausal women
3. men over age 50

In addition to the effects of bed rest we will also examine the effects of sleep deprivation (another condition of space flight). We will also evaluate the effects of the alpha-agonist midodrine as a countermeasure to the development of orthostatic intolerance. We may also evaluate a countermeasure to the development of ventricular arrhythmias.

The key technologies we will utilize are Cardiovascular System Identification (CSI) as a noninvasive means of assessing closed-loop cardiovascular regulation, and measurement of microvolt T-wave alternans (MTWA) as a noninvasive measurement of changes in cardiac repolarization which has been shown in clinical trials to be an accurate measure to susceptibility to ventricular arrhythmias.

To date in this project, we have found that CSI measures of autonomically mediated cardiovascular reflexes are diminished by bed rest, and that during bed rest there appears to be a shift towards increasing sympathetic/parasympathetic balance. We have found that pre-bedrest CSI measures of increased sympathetic/parasympathetic balance identify those subjects who tolerate tilt both pre-bedrest and post-bedrest. We have put considerable effort into improving CSI technology for use in these studies and for application in biomedical research and patient monitoring.

We have demonstrated that the alpha-agonist midodrine appears to be an effective countermeasure to the development of orthostatic intolerance after exposure to 16 days of simulated microgravity.

We have found that even 16 days of bed rest tends to induce sustained MTWA although not at a level that would be of immediate clinical concern. This evidence does indicate that bed rest does measurably alter cardiac repolarization processes, and raises the issue of whether long term exposure to microgravity could increase susceptibility to ventricular arrhythmias. We have also recently conducted a clinical study that demonstrates that MTWA is an accurate predictor of susceptibility to ventricular arrhythmias and sudden cardiac death in patients with heart failure and no prior history of sustained ventricular arrhythmias.

We plan to continue our ground-based studies in the above identified patient groups, and evaluate the effects of sleep deprivation and midodrine countermeasures. We may also test a proposed countermeasure to the development of ventricular arrhythmias pending future results from these studies. In addition, we have submitted a flight proposal to measure CSI and MTWA pre and post flight, and to evaluate the midodrine countermeasure during flight conditions.

We plan to develop further the CSI and MTWA technologies for use on earth for biomedical research and clinical applications.

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This project's funding ended in 2004