Cardiovascular Effects of Simulated Microgravity in Man
Joint Agency Name:
PI Name:
Cohen, Richard J
PI Phone:
617-253-7430
PI Email:
rjcohen@mit.edu
Fax:
617-253-3019
PI Organization Type:
UNIVERSITY
Organization Name:
Massachusetts Institute of Technology
PI Address 1:
Room E25-335a, 45 Carleton Street
PI Address 2:
Massachusetts Institute of Technology
City:
Cambridge
State:
MA
Zip Code:
02142
Congressional District:
8
Comments:
Project Type:
GROUND
Solicitation:
NSBRI
Start Date:
10/01/2000
End Date:
09/30/2003
No. of Post Docs:
2
No. of PHD Degree:
No. of Phd Students:
3
No. of MS Degree:
No. of MS Students:
3
No. of BS Degree:
No. of BS Students:
1
Monitoring Center:
NSBRI
Contact Monitor:
Contact Phone:
Contact Email:
Nag No.:
None
Former PI Name:
Performance Goal No.:
Performance Goal Text:
Task Description:
Many astronauts after being weightless in space become hypotensive and presyncopal upon assuming an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and following spaceflight, and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced following long-term spaceflight (1) and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. This problem has also been observed to be more pronounced among women than among men (2). In addition to the problem of post-flight orthostatic intolerance, a variety of heart rhythm disturbances have been observed in astronauts during and after space flight (3-6). The potential lethal arrhythmic risk for astronauts is sustained ventricular tachycardia or ventricular fibrillation, while non-sustained ventricular tachycardia could cause syncope. Older individuals, particularly men, may be most susceptible to ventricular arrhythmias during flight.
In previous ground based bed-rest studies sponsored by NSBRI we have applied two new techniques that we have developed to study the effects of simulated microgravity on the cardiovascular system. Cardiovascular system identification (CSI) has been used a non-invasive means of measuring alterations in closed-loop cardiovascular regulation and the measurement of microvolt level T wave alternans (TWA)has been used as a non-invasive measure of susceptibility to ventricular arrhythmias. We have also successfully tested the alpha-1 sympathetic agonist midodrine as a countermeasure to the development of orthostatic intolerance. We have found that 16 days of bed-rest results in altered cardiovascular regulation in particular alterations in baroreceptor sensitivity, altered electrical stability of the heart, and that midodrine is an effective countermeasure to the development of orthostatic hypotension.
In this project we apply the same measurement techniques of CSI and TWA to two groups of subjects before and after 16 days of bedrest. Premenopausal women and men over age 55. The women will be randomized to placebo or midodrine to see if this countermeasure is effective in these subjects who are more susceptible to orthostatic hypotension than men of the same age. The group of older men will be randomized to placebo or spironolactone, an aldosterone blocking agent. Spironolactone will be evaluated as a countermeasure to the pro-arrhythmic action of aldosterone which is elevated in these subjects during bed rest.
Task Objective:
Task Significance:
Task Progress:
Research progress was made in each of the following areas. Detail is available in the 31 journal publications listed in the bibliography.
1. Midodrine Countermeasure to the Development of Orthostatic Intolerance After Simulated Microgravity
2. Effect of Gender on Orthostatic Tolerance
3. Cardiovascular System Identification (CSI) of Subjects Undergoing Head-Down Tilt Bed Rest
4. Development of CSI Means of Separately Measuring Sympathetic and Parasympathetic Responsiveness
5. Application of New CSI Measures of Sympathetic and Parasympathetic Responsiveness
6. CSI Measures of Sympathetic and Parasympathetic Responsiveness and Tilt Tolerance Pre Bed Rest
7. Prediction of Tilt Tolerance after Bed Rest from Pre Bed Rest CSI Measures
8. CSI Measures of Arterial Total Peripheral Resistance (TPR) Baroreflex and Cardiopulmonary TPR Baroreflex
9. Changes in Arterial and Cardiopulmonary Baroreflexes with Bed Rest
10. Validation of CSI Measures by Means of Computer Simulation and Analysis of Animal Data
11. Development of Technology for Non-invasive Continuous Cardiac Output Monitoring
12. Principal Components Approach to System Identification
13. Calf Plethysmography in Subjects Before and After Simulated Microgravity
14. Microvolt T-Wave Alternans in Subjects Exposed to Simulated Microgravity
15. Microvolt T-Wave Alternans in Clinical Patient Populations
Earth Benefits:
To conduct these studies we have developed two new technologies: the measurement of Microvolt T Wave Alternans (MTWA) and Cardiovascular System Identification (CSI).
MTWA has already been commercialized, cleared by the FDA a non-invasive predictor of cardiac arrest and sudden cardiac death, and has been issued a reimbursement code by Medicare. It is in widespread and growing clinical use, and is already having an impact in reducing mortality from sudden cardiac death - the cause of one in seven of all deaths in the United States.
Cardiovascular System Identification is a powerful non-invasive technique for assessing closed loop cardiovascular regulation and autonomic activity. It has applications as a diagnostic technique, and as a means to guide therapy, for a wide range of disorders including heart failure, hypertension and diabetes.
NSCORT Background/History:
Flight Program:
Flight Assignment:
Bibliography Type:
Description: (Last Updated: 02/27/2004)
Articles in Peer-reviewed Journals
Aljuri AN. "System Identification of Dynamic Closed-Loop Cardiovascular Control of Total Peripheral Resistance by Arterial and Cardiopulmonary Baroreceptors" Harvard-MIT Division of Health Sciences and Technology. Cambridge: Massachusetts Institute of Technology, Oct-2002
Articles in Peer-reviewed Journals
Armoundas AA, Ju K, Iyengar N, et al. "A stochastic nonlinear autoregressive algorithm reflects nonlinear dynamics of heart-rate fluctuations" Ann Biomed Eng 2002; 30:192-201, Oct-2002
Articles in Peer-reviewed Journals
Bloomfield DM, Hohnloser SH, Cohen RJ. "Interpretation and classification of microvolt T wave alternans tests." J Cardiovasc Electrophysiol 2002; 13:502-12, Oct-2002
Articles in Peer-reviewed Journals
Cheung MM, Weintraub RG, Cohen RJ, Karl TR, Wilkinson JL, Davis AM. "T wave alternans threshold late after repair of tetralogy of Fallot." J Cardiovasc Electrophysiol 2002; 13:657-61. , Oct-2002
Articles in Peer-reviewed Journals
Mukkamala R, Cohen RJ, Mark RG. " computational model-based validation of Guytons analysis of cardiac output and venous return curves" Computers in Cardiology 2002; 29:561-564. , Oct-2002
Articles in Peer-reviewed Journals
Mukkamala R, Xiao X, Cohen RJ "A model order selection criterion for the identification of physiologic systems, " Proceedings of the Second Joint EMBS/BMES Conference, Houston, 2002; 177-178. , Oct-2002
Articles in Peer-reviewed Journals
Xiao X, Mukkamala R, Sheynberg N, Williams GH, Cohen RJ "of prolonged bed rest on the total peripheral resistance baroreflex." Computers in Cardiology 2002; 29:53-56, Oct-2002
Articles in Peer-reviewed Journals
Xiao X, Mukkamala R, Sheynberg N, Maa M, Williams GH, Cohen RJ "tone is impaired by prolonged bedrest and sympathetic tone before bedrest predicts tolerance to tilt after bedrest" Proceedings of the Second Joint EMBS/BMES Conference, Houston, 2002; 2172-2173. , Oct-2002
Articles in Peer-reviewed Journals
Mukkamala R, Toska K, Cohen RJ. "Noninvasive identification of the total peripheral resistance baroreflex." Am J Physiol Heart Circ Physiol 2003; 284:H947-59, Jan-2003
Articles in Peer-reviewed Journals
Hohnloser SH, Ikeda T, Bloomfield DM, Dabbous OH, Cohen RJ. "T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation" The Lancet 2003; 362:125-126. , Jan-2003
Articles in Peer-reviewed Journals
Hohnloser SH, Klingenheben T, Bloomfield D, Dabbous O, Cohen RJ. " Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study" J Am Coll Cardiol 2003; 41:2220-4. , Jan-2003
Articles in Peer-reviewed Journals
Xiao X, Mukkamala R, Cohen RJ. " A weighted principal component regression approach for system identification, " IEEE Workshop on Statistical Signal Processing, St. Louis, MO, 2003; accepted for publication. , Jan-2003
