Abstract
The current study tested the hypothesis that ischemia-reperfusion (I-R) can cause more severe myocardial dysfunction and oxidative damage in senescent rats than young adult rats. Male Fischer 344 rats at the age of 6 (adult) and 24 (old) months were subjected to an open-chest heart surgery and randomly assigned to one of the following treatments: Ischemia only (I), with the occlusion of the main descending branch of the left coronary artery (LCA) for 30 min; I-R, with the release of LCA occlusion for 20 min; or sham (S) operation. Heart mechanical performance was monitored using a fluid-filled catheter inserted in the right carotid artery and advanced to the left ventricle. Ischemia caused similar reductions of left ventricle systolic pressure (LVSP) and contractility (± dP/dt) in adult and aged hearts. After I-R, adult hearts regained 82% (P < 0.05) of the pre-ischemic LVSP, whereas the aged hearts regained 91% (P > 0.05) of LVSP. There was no significant difference in the reduction of ± dP/dt with I-R between adult and aged hearts. Old rats had lower pre-ischemic heart rate than adult rats, however, I-R caused no reduction of heart rate, and a smaller reduction of pressure-rate double product in the aged rats (10%, P > 0.05) than the adult rats (23%, P < 0.01). Aged rats demonstrated greater myocardial and plasma glutathione (GSH) concentrations prior to surgery, and maintained higher GSH levels and GSH:glutathione disulfide (GSSG) ratio with I-R. Aged hearts also had higher GSH peroxidase, GSH reductase and GSH sulfur-transferase activities than adult hearts, while I-R induced lipid peroxidation was similar. It is concluded that senescent hearts with intact circulatory and neural inputs are not more susceptible to I-R injury than adult hearts during myocardial I-R, partly because they have a greater GSH antioxidant protection.
Original language | English (US) |
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Pages (from-to) | 503-518 |
Number of pages | 16 |
Journal | Mechanisms of Ageing and Development |
Volume | 122 |
Issue number | 6 |
DOIs | |
State | Published - May 15 2001 |
Externally published | Yes |
Bibliographical note
Funding Information:The present research was supported in part by a grant-in-aid from the American Heart Association National Center and AHA Wisconsin Affiliate. The Fischer 344 rats were generously supplied through an NIA/NIH dissertation research support grant. The authors wish to thank J. Hollander and D. Powers for their technical assistance.
Keywords
- Age
- Antioxidant
- Glutathione
- Heart
- Hemodynamic
- Ischemia-reperfusion
- Oxidative stress