Atorvastatin preconditioning improves the forward blood flow in the no-reflow rats

Fundam Clin Pharmacol. 2014 Feb;28(1):42-52. doi: 10.1111/j.1472-8206.2012.01074.x. Epub 2012 Sep 18.

Abstract

Atorvastatin is not only an antilipemic but also used as an anti-inflammatory medicine in heart disease. Our working hypothesis was that atorvastatin preconditioning could improve the forward blood flow in the no-reflow rats associated with inflammation. We investigated that two doses of atorvastatin preconditioning (20 and 5 mg/kg/day) could alleviate deterioration of early cardiac diastolic function in rats with inflammation detected by echocardiography and haemodynamics. This benefit was obtained from the effect of atorvastatin preconditioning on improving forward blood flow and preserving the infarct cardiomyocytes, which was estimated by Thioflavin S and TTC staining in rats with myocardial ischemia/reperfusion. Subsequently, the improving of forward blood flow was ascribed to reduction of microthrombus in microvascular and myocardial fibrosis observed by MSB and Masson's trichrome staining with atorvastatin preconditioning. Ultimately, we found that atorvastatin preconditioning could reduce inflammation factor, such as tumor necrosis factor-α and fibrinogen-like protein 2, both in myocardial and in mononuclear cells, which probably attribute to microcirculation dysfunction in no-reflow rats detected by immunohistochemistry staining, western blot, and ELISA detection, respectively. In conclusion, atorvastatin preconditioning could alleviate deterioration of early cardiac diastolic function and improve the forward blood flow in the no-reflow rats attributing to reduction of TNF-α and fgl-2 expression.

Keywords: atorvastatin; fibrinogen-like protein 2; myocardial ischemia/reperfusion; no-reflow; tumor necrosis factor-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin
  • Echocardiography / methods
  • Fibrinogen / metabolism
  • Fibrosis / drug therapy
  • Fibrosis / metabolism
  • Hemodynamics / drug effects
  • Heptanoic Acids / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Microcirculation / drug effects*
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / metabolism
  • Myocardium / metabolism
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / drug effects*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Heptanoic Acids
  • Pyrroles
  • Tumor Necrosis Factor-alpha
  • fibrinogen-like protein 2, rat
  • Fibrinogen
  • Atorvastatin