Cardioprotective effects of cyclosporine A in an in vivo model of myocardial ischemia and reperfusion.

Abstract

Recent evidence indicates that reperfusion of the heart after a period of ischemia leads to the opening of the mitochondrial permeability transition pore (MPTP). The aim of this study was to investigate cardioprotective effects of cyclosporine A (CsA), an inhibitor of the MPTP, in an in vivo model of myocardial ischemia and reperfusion. Male Sprague-Dawley rats were subjected to occlusion of the left anterior descending coronary artery for 30 min followed by 180 min of reperfusion. CsA (10 mg/kg) or vehicle was given 10 min prior to ischemia via the femoral vein. Sham myocardial ischemia-reperfusion rats (sham-operation group) were used as controls. Infarct size was measured using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride) and myocardial apoptosis by caspase-3 activity was determined by fluorescent assay. The myocardium mitochondria ultrastructure was observed through a transmission electron microscope. CsA significantly reduced infarct size (48.8 +/- 5.8% of left ventricle in vehicle + I/R group and 30.3 +/- 2.7% of left ventricle in CsA + I/R, respectively) and decreased caspase-3 activity in the myocardium [(0.62 +/- 0.17)/microg of protein and (0.42 +/- 0.15)/microg of protein, respectively] and relieved the injury of mitochondria. CsA reduced the cardiac damage associated with ischemia-reperfusion injury of the heart. The cardioprotective effects of CsA might be associated with the protection of mitochondria and the inhibition of caspase-3 activity. It also suggests that the MPTP might play an important role in cardiomyocytes death after ischemia-reperfusion injury.