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Mechanisms of AIDS and cocaine related cardiovascular disease

Chaves, Alysia Anne
http://rave.ohiolink.edu/etdc/view?acc_num=osu1056031201

Abstract Details

2003, Doctor of Philosophy, Ohio State University, Pharmacy.
The primary focus of this thesis deals with understanding pathophysiological aspects of retrovirus (HIV/AIDS) and cocaine related cardiovascular complications. Central goals were to define important interactions between the cardiovascular and immune systems and involvement of oxidant related pathways in relevant animal models and in human tissues. Additional components of this dissertation were to define optimal conditions for cardiovascular performance assessments (contractility and electrophysiology) in mouse models and to develop novel mechanistic insights so that therapy could be further optimized. Using a relevant mouse model of retroviral pathogenesis (LPBM5, “murine AIDS” model) we observed time dependent cardiomyopathy and first-time evidence of reactive nitrogen species in cardiac tissue in this setting; we also corroborated these phenomena in a well-defined set of human tissues from HIV/AIDS autopsy cases. In subsequent investigations we found that a modest exposure of bacterial lipopolysaccharide amplified abnormalities in cardiac structure and function observed in the murine AIDS model, and that this synergistic effect was associated with increased cardiac prevalence of activated monocytes and cardiac myocyte expression of toll-like receptor 4 (TLR4, an important component of cardiac innate immunity). These observations suggest that coincident infection in humans may promote HIV-related cardiac complications. In separate studies we investigated mechanistic aspects of cocaine related cardiovascular toxicity in mice. A single dose of cocaine (30mg/kg) caused acute and protracted electrical abnormalities and protracted endothelial dysfunction in mice, analogous to clinical phenomenon observed in humans. Isolated cell experiments demonstrated that cocaine induced toxicity is related to increased cellular production of oxidants (in the absence of hypoxia). In a pilot clinical study we also investigated the effects of a standardized grape product with respect to vascular performance in normal subjects. We found that this product produced beneficial effects on endothelial function (using a noninvasive ultrasound method of evaluation) and that these were not ethanol-dependent and could protect against detrimental influences of a standard high fat meal. Collectively these studies demonstrate an important role for oxidant related and immune system mediated processes in diverse settings of cardiac and vascular dysfunction.
John Bauer (Advisor)
Health Sciences, Pharmacology
HIV; retrovirus; LP-BM5; murine AIDS; reactive nitrogen species; cocaine; cardiovascular; endothelium; oxidants; brachial artery ultrasound; grapes

Recommended Citations

Citations

  • Chaves, A. A. (2003). Mechanisms of AIDS and cocaine related cardiovascular disease [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1056031201

    APA Style (7th edition)

  • Chaves, Alysia. Mechanisms of AIDS and cocaine related cardiovascular disease. 2003. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1056031201.

    MLA Style (8th edition)

  • Chaves, Alysia. "Mechanisms of AIDS and cocaine related cardiovascular disease." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1056031201

    Chicago Manual of Style (17th edition)

osu1056031201
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© 2003, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.