Simvastatin-induced myocardial protection against ischemia-reperfusion injury is mediated by activation of ATP-sensitive K+ channels

Shahin Tavackoli, Taras Ashitkov, Zhao Yong Hu, Massoud Motamedi, Barry F. Uretsky, Yochai Birnbaum

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Objectives: Previous studies have suggested that the 3-hydroxy-3- methylglutaryl coenzyme A reductase inhibitors attenuate ischemia-reperfusion injury. We investigated whether pretreatment with simvastatin reduces myocardial infarct size and whether glyburide, a non-selective inhibitor of the ATP-sensitive K+ channels, abrogates this infarct size-limiting effect. Methods: Sprague-Dawley rats were treated with either simvastatin (20 mg/kg per day) or saline alone for 3 days. Additional groups of rats were treated as above and on the fourth day they received intravenous glyburide (0.3 mg/kg). All rats underwent 30 min of coronary artery occlusion followed by 180 min of reperfusion. Ischemic myocardium at risk was assessed with blue dye and infarct size with triphenyltetrazolium chloride. Results: Infarct size, expressed as a percentage of the myocardium at risk, was significantly smaller in the simvastatin group (n = 8, 20.8 ± 3.4%) than in the placebo group (n = 6, 40.1 ± 2.7%) (P = 0.001). Glyburide abolished the protective effect of simvastatin with infarct size being 34.2 ± 6.9% and 29.7 ± 3.9% of the area at risk in the simvastatin group (n = 7) and placebo (n = 7) group, respectively (P = 0.58). Conclusions: Simvastatin significantly reduced myocardial infarct size. The protective effect was completely abrogated by glyburide, strongly suggesting that this protective effect is mediated via activation of the ATP-sensitive K+ channels.

Original languageEnglish (US)
Pages (from-to)53-58
Number of pages6
JournalCoronary Artery Disease
Volume15
Issue number1
DOIs
StatePublished - Feb 2004

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Keywords

  • ATP-sensitive K channel
  • Ischemia
  • Myocardial infarction
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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