Computational models of cardiovascular response to orthostatic stress

The cardiovascular response to changes in posture has been the focus of numerous investigations in the past. Yet despite considerable, targeted experimental effort, the mechanisms underlying orthostatic intolerance (OI) following spaceflight remain elusive. The number of hypotheses still under consideration and the lack of a single unifying theory of the pathophysiology of spaceflight-induced OI testify to the difficulty of the problem. In this investigation, we developed and validated a comprehensives lumped-parameter model of the cardiovascular system and its short-term homeostatic control mechanisms with the particular aim of simulating the short-term, transient hemodynamic response to gravitational stress. Our effort to combine model building with model analysis led us to conduct extensive sensitivity analyses and investigate inverse modeling methods to estimate physiological parameters from transient hemodynamic data. Based on current hypotheses, we simulated the system-level hemodynamic effects of changes in parameters that have been implicated in the orthostatic intolerance phenomenon. Our simulations indicate that changes in total blood volume have the biggest detrimental impact on blood pressure homeostasis in the head-up posture. If the baseline volume status is borderline hypovolemic, changes in other parameters can significantly impact the cardiovascular system's ability to maintain mean arterial pressure constant. In particular, any deleterious changes in the venous tone feedback impairs blood pressure homeostasis significantly. This result has important implications as it suggests that al-adrenergic agonists might help alleviate the orthostatic syndrome seen post-spaceflight.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Heldt, Thomas, 1972-

Advisor dc:contributor.advisor

• Roger G. Mark.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/28761

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/28761