A redox-based mechanism for cardioprotection induced by ischemic preconditioning in perfused rat heart

W. Chen, S. Gabel, C. Steenbergen, E. Murphy

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

Recent studies have suggested that mild redox alterations can regulate cell function. Therefore, we tested the hypothesis that alteration in the thiol redox state might be responsible for the cardioprotective effects conferred by ischemic preconditioning in the perfused rat heart. We find that preconditioning with four 5-minute periods of ischemia, each separated by 5 minutes of reflow, is associated with a significant loss of glutathione (3.98 ± 0.32 μmol/g dry wt, n = 8) compared with no preconditioning (6.38 ± 0.24 μmol/g dry wt, n = 14). We further find that the addition of N- acetylcysteine (NAC, a glutathione precursor and antioxidant) during the preconditioning protocol not only blocks the loss of glutathione (5.60 ± 0.31 μmol/g dry wt, n = 9) but also blocks the predictive effects of preconditioning. It is observed that after 20 minutes of ischemia followed by 20 minutes of reflow, untreated hearts recover 38 ± 7% (n = 5) of their initial preischemic contractile function, whereas preconditioned hearts recover 91 ± 11% (n = 7). Hearts preconditioned in the presence of NAC recover 24 ± 3% (n = 7) of their preischemic function. Similarly, the addition of NAC reverses the protective effect of preconditioning on creatine kinase release. On reflow after 60 minutes of ischemia, creatine kinase release from control hearts was 271 ± 20 IU · 20 min-1 · g dry wt-1 (n = 5), whereas preconditioned hearts release only 170 ± 26 IU · 20 min-1 · g dry wt-1 (n = 6), and hearts preconditioned in the presence of NAC release 361 ± 30 IU · 20 min-1 · g dry wt-1 (n = 5). We also find that hearts preconditioned in the presence of NAC have less attenuation of the decline in pH, than hearts preconditioned in the absence of drug. Thus, a redox-sensitive mechanism may be involved in the protection afforded by ischemic preconditioning.

Original languageEnglish (US)
Pages (from-to)424-429
Number of pages6
JournalCirculation research
Volume77
Issue number2
DOIs
StatePublished - Aug 1995

Keywords

  • glutathione
  • ischemia/reperfusion
  • preconditioning
  • thiol redox

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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