Nicole S. Wayman, Belinda L. Ellis, Christoph Thiemermann
Med Sci Monit 2003; 9(5): BR155-159
Available online: 2003-05-22
Background: This study was designed to investigate the effects of simvastatin in a rat model of acute myocardial infarction.
Material/Methods: Male Wistar rats were anesthetized (thiopentone sodium 120 mg/kg). After a thoracotomy, the left-anterior-descending coronary artery (LAD) was occluded (for 25 min) and reperfused (for
120 min). Area at risk (AR) was determined with Evans Blue dye and infarct size after staining of the area at risk with nitroblue tetrazolium.
Results: In rats, which received the vehicle for simvastatin (10% DMSO, 1 ml/kg i.v. at 1 h prior to the occlusion of the LAD), occlusion of the LAD for 25 min followed by reperfusion for 2 hours
resulted in an infarct size of 54±4% (n=7) of the AR. When compared with vehicle, administration of simvastatin (1 mg/kg i.v. bolus administration at 1 h prior to the onset of myocardial
ischemia) caused a significant reduction in myocardial infarct size of 39%. LAD-occlusion and reperfusion caused a progressive fall in mean arterial blood pressure (when compared with sham-operated animals). Simvastatin had no significant effect on blood pressure.
Conclusions: The result indicates that simvastatin, an inhibitor of HMG-CoA reductase and a ligand of PPAR-α and PPAR-γ, reduces the tissue necrosis associated with acute myocardial infarction.
We propose that statins may be useful in conditions associated with ischemia-reperfusion of the heart and other organs.
Keywords: Animals, Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology, Myocardial Infarction - pathology, Myocardial Infarction - prevention & control, Myocardial Ischemia - drug therapy, Myocardial Ischemia - pathology, Myocardial Reperfusion Injury - pathology, Myocardial Reperfusion Injury - prevention & control, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear - agonists, Simvastatin - pharmacology, Transcription Factors - agonists