Cerivastatin and hypercholesterolemia reduce apoptosis of cardiomyocytes in guinea pig papillary muscle subjected to hypoxia/reoxygenation

Pharmacol Rep. 2006 May-Jun;58(3):420-6.

Abstract

The aim of this study was to assess how cerivastatin influences contractility and degree of myocardial damage in papillary muscle subjected to hypoxia-reoxygenation in hypercholesterolemic guinea pigs. Study group consisted of guinea pigs, fed standard, hypercholesterolemic or hypercholesterolemic diets with low dose of cerivastatin. During experimental hypoxia-reoxygenation, the contractility was measured. Apoptosis of cardiomioctes was assessed with the use of TUNEL technique. Total cholesterol in standard, hypercholesterolemic and cerivastatin-treated group was 35 +/- 8 mg/dl, 131.6 +/- 30.4 mg/dl and 121.2 +/- 26.2 mg/dl, respectively, and was significantly higher in rats fed hypercholesterolemic and hypercholesterolemic + cerivastatin diets than in control group (p < 0.01). There were no significant differences between all analyzed groups in the post-ischemic cardiac function. Percentage of apoptotic cells after hypoxia-reoxygenation injury in groups fed standard, hypercholesterolemic and hypercholesterolemic + cerivastatin diets was 30 +/- 8%, 20 +/- 4% and 5 +/- 7%, respectively, and was significantly lower in groups that received hypercholesterolmic (p < 0.01) and hypercholesterolemic + cerivastatin (p < 0.001) diets in comparison with standard diet-fed group. In the group treated with cerivastatin, the percentage of apoptotic cells was additionally lower in comparison with hypercholesterolemic group (p < 0.01). Negative correlation between percentage of apoptotic cells and HDL level was found when all groups were considered jointly (r = -0.41, p < 0.05). Our study clearly shows that cerivastatin in hypercholesterolemic animals and hypercholesterolemia itself limit cardiomiocyte damage after hypoxia-reoxygenation.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cholesterol, Dietary / pharmacology
  • Guinea Pigs
  • Hypercholesterolemia / pathology*
  • Hypoxia / physiopathology*
  • In Situ Nick-End Labeling
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Reperfusion Injury / physiopathology*
  • Myocytes, Cardiac / drug effects*
  • Papillary Muscles / cytology
  • Papillary Muscles / drug effects
  • Pyridines / pharmacology*

Substances

  • Cholesterol, Dietary
  • Pyridines
  • cerivastatin