Regional Myocardial Ischemia Reperfusion Injury in Vivo: The Role of Glutathione
Leichtweis, Steven Boyd
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Permalink
https://hdl.handle.net/2142/86363
Description
Title
Regional Myocardial Ischemia Reperfusion Injury in Vivo: The Role of Glutathione
Author(s)
Leichtweis, Steven Boyd
Issue Date
2002
Doctoral Committee Chair(s)
Boileau, Richard A.
Department of Study
Kinesiology and Community Health
Discipline
Kinesiology and Community Health
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Rehabilitation and Therapy
Language
eng
Abstract
The efficacy of glutathione (GSH) in protecting against ischemia-reperfusion (I-R) induced myocardial dysfunction and oxidative stress was addressed in three studies utilizing an open-chest rat model of regional, myocardial PR injury. Three major findings resulted from the first study which assessed aging, myocardial GSH status, and I-R injury. First, aged rats have a higher myocardial GSH level than adult rats. Second, during myocardial I-R the liver exports GSH into plasma, increasing the plasma GSH pool and enhancing myocardial antioxidant protection specifically at the level of the endothelial cell layer where a majority of the potential oxidants are generated. Third, adult and aged rats subjected to regional, myocardial I-R sustain similar levels of cardiovascular dysfunction and cellular oxidative damage. The second study investigated the effects of GSH depletion during myocardial I-R injury and resulted in two major findings. First, GSH deficient rats were at greater risk of cardiovascular dysfunction and oxidative damage following I-R compared to GSH adequate rats. Second, treatment by acivicin did not result in greater oxidative damage in GSH depleted rats even though these rats showed the greatest level of cardiovascular dysfunction following I-R. The third study explored the potential of GSH and other sulfhydryl compounds as potential protective supplements during I-R injury and produced two major findings. First, although sulfhydryl supplementation did not prevent cardiovascular dysfunction in rats subjected to I-R, two of the supplemented compounds prevented an increase in myocardial lipid peroxidation. Second, none of the supplemented compounds increased myocardial GSH content. Overall, the model used in these studies serves a valuable link between basic cardiovascular research on mechanisms of I-R induced cellular damage and clinical outcomes. Importantly, myocardial GSH status is not independent from the rest of the body. GSH homeostasis is a dynamic interaction between all organs and tissues. Acute myocardial I-R results in oxidative stress to the heart and a challenge to whole-body GSH homeostasis. This research provides key insights into GSH utilization during myocardial I-R injury under physiological (aging), pharmacological (depletion), and nutritional (supplementation) intervention.
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