Reduction of myocardial infarct size by fluvastatin

Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H59-64. doi: 10.1152/ajpheart.00782.2002. Epub 2003 Mar 6.

Abstract

Statins have a variety of cardioprotective properties following chronic treatment. In contrast, little is known about the acute effects. Reperfusion acutely injures the heart by activation of neutrophils as well as endothelial cells. Because statins are known to influence the processes pathogenetically involved, we hypothesized that acute application of statins attenuates the sequelae of cardiac reperfusion. In rats, myocardial infarction (MI) was induced by ligature of the left coronary artery followed by reperfusion. Myocardial blood flow (MBF) was determined by H2 clearance and regional myocardial function (fractional thickening, FT) by pulsed Doppler. MI size was measured by triphenyltetrazolium chloride (TTC) staining, neutrophil extravasation by determination of myeloperoxidase (MPO) activity, and nitric oxide generation via measurement of cGMP. Treatment with fluvastatin, administered intravenously 20 min before the onset of ischemia, significantly attenuated the decline of FT and MBF at the end of the reperfusion period and significantly reduced MI size. Furthermore, fluvastatin induced a significant reduction of MPO activity and an increase of cGMP level compared with the control group. The effect of fluvastatin was completely abolished following pretreatment of NG-nitro-l-arginine methyl ester (l-NAME). These findings suggest that acute application of fluvastatin reduces MI size and attenuates reperfusion injury. We propose that the underlying mechanism is at least partially an inhibition of inflammation and endothelial dysfunction by preventing the activation and extravasation of neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / physiology
  • Coronary Circulation / drug effects
  • Coronary Vessels / physiology
  • Cyclic GMP / metabolism
  • Echocardiography, Doppler, Pulsed
  • Enzyme Inhibitors / pharmacology
  • Fatty Acids, Monounsaturated / therapeutic use*
  • Female
  • Fluvastatin
  • Heart Rate / physiology
  • Hydrogen / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Indoles / therapeutic use*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control
  • Myocardium / pathology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neutrophil Infiltration / drug effects
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type III
  • Peroxidase / metabolism
  • Rats
  • Rats, Inbred WF
  • Ventricular Function, Left / physiology

Substances

  • Enzyme Inhibitors
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Nitric Oxide
  • Fluvastatin
  • Hydrogen
  • Peroxidase
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Cyclic GMP
  • NG-Nitroarginine Methyl Ester