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Project Title:
Clinical Centers for the Clinical Network for the Treatment of Adult Respiratory
Distress Syndrome
Funding Agency:
National Institutes of Health
Total Project Period:
Oct 31, 2000 - Oct 31, 2004
Principal Investigator:
Juan Puyana, MD (Michael Donahoe, MD, Program Director)
Co-Investigator(s):
Mitchell P. Fink, MD
Project Summary:
The close correlation between the output of the mathematical model of inflammation and animal data suggests that a common metabolic and inflammatory response underlies diverse shock states, raising the possibility of modeling the inflammatory process in vivo. In contrast, circulatory collapse involves the inflammatory processes we have modeled, but also neuro-endocrine and cardiovascular derangements not currently in our mathematical model. The literature suggests two main paradigms of cardiovascular collapse: severe hemorrhage of short duration (approximately 1-2 hours), and a more subdued, continuous hemorrhage lasting 4-8 hours. {Peitzman, Billiar, et al. 1995 113 /id} This proposal will address both of these paradigms, in a systematic fashion in mice under Specific Aim 1 and in a more focused, therapeutically relevant fashion in swine under Specific Aim 2. Our studies show that we can, on the one hand, use a mathematical model informed by inflammatory parameters to predict dysfunction, and, on the other hand, measure dysfunction non-invasively in terms of clinically relevant parameters but without clear correlation with underlying inflammation. We hypothesize that inflammation is a crucial component of circulatory collapse. We further hypothesize that our current mathematical model, augmented to include relevant neuro-endocrine, cardiovascular, and metabolic components, can predict the point at which this collapse is irreversible.
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