Effects of acute and chronic atorvastatin on cardioprotection of ischemic postconditioning in isolated rat hearts

Cardiovasc Ther. 2013 Aug;31(4):187-92. doi: 10.1111/j.1755-5922.2012.00318.x.

Abstract

Background: Myocardial reperfusion therapy remains the most effective strategy to limit infarct size and improve clinical outcome. However, reperfusion injury is still inevitable, and a number of strategies have been developed to ameliorate its lethal outcome. The beneficial roles of ischemic postconditioning (Ipost) have regained more interest in targeting myocardial reperfusion phase to improve cardioprotection.

Aims: This study was to determine whether acute or chronic treatment with atorvastatin affects cardioprotection when it was combined with Ipost.

Results: Acute or chronic atorvastatin treatment significantly reduced infarct size and recovered contractile dysfunction during reperfusion. When Ipost was combined with atorvastatin treatment, chronic, but not acute, atorvastatin therapy attenuated the cardioprotective effects of Ipost. Chronic, but not acute, atorvastatin treatment also abolished Ipost-induced phosphorylation level of Akt and endothelial nitric oxide synthase (eNOS).

Conclusions: Chronic atorvastatin treatment could interfere with cardioprotective effects of Ipost on limiting infarct size and contractile dysfunction, possibly via inhibition of Akt and eNOS activity. This study suggests that Ipost should be used carefully when atorvastatin is taken by patients with AMI.

Keywords: Atorvastatin; Ischemia-reperfusion injury; Ischemic postconditioning; Isolated heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin
  • Cardiotonic Agents / administration & dosage*
  • Drug Administration Schedule
  • Hemodynamics / drug effects
  • Heptanoic Acids / administration & dosage*
  • In Vitro Techniques
  • Ischemic Postconditioning*
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrroles / administration & dosage*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Cardiotonic Agents
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Proto-Oncogene Proteins c-akt