Aged rat hearts are not more susceptible to ischemia-reperfusion injury in vivo: Role of glutathione

Steve Leichtweis, Christiaan Leeuwenburgh, Jeff Bejma, Li Li Ji

Research output: Contribution to journalArticle

19 Scopus citations

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 languageEnglish (US)
Pages (from-to)503-518
Number of pages16
JournalMechanisms of Ageing and Development
Volume122
Issue number6
DOIs
StatePublished - May 15 2001
Externally publishedYes

Keywords

  • Age
  • Antioxidant
  • Glutathione
  • Heart
  • Hemodynamic
  • Ischemia-reperfusion
  • Oxidative stress

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