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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Xie
J-R
JR
Department of Anesthesiology, Sir Run Run Shaw Hospital, Hangzhou, China.
Yu
L-N
LN
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents; D053148:Caspase 3 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D053148:Caspase 3