Simvastatin reduces infarct size in a model of acute myocardial ischemia and reperfusion in the rat.
BACKGROUND
This study was designed to investigate the effects of simvastatin in a rat model of acute myocardial infarction.


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-a and PPAR-g, 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.
Wayman
Nicole S
NS
The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine, UK.
Ellis
Belinda L
BL
Thiemermann
Christoph
C
D000818:Animals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D019821:Simvastatin / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019821:Simvastatin