Pharmacological Postconditioning Protects Isolated Rat Hearts Against Ischemia-Reperfusion Injury: The Role of Mitochondrial Permeability Transition Pore

Postconditioning has been verified to provide cardioprotection and is associated with the state of mitochondrial permeability transition pore. However, there are a few limitations with clinical use of classic postconditioning; therefore, the purpose of this investigation was to study whether inhibition of mitochondrial permeability transition pore opening with cyclosporine A also provided cardioprotection. Langendorff-perfused Sprague-Dawley rat hearts were perfused for 20 minutes with Krebs-Henseleit buffer followed by 30 minutes of crystalloid cardioplegia and 60 minutes of reperfusion. Control hearts (Con group) were reperfused with Krebs-Henseleit buffer. Postconditioning hearts (Ipo group) were with six cycles of 10 seconds reocclusion separated by 10 seconds perfusion before reperfusion. Cyclosporine A postconditioning hearts (CsA group) were reperfused with Krebs-Henseleit buffer containing 0.8 mu mol/L cyclosporine A at first 5 minutes of reperfusion. Compared with Con group, myocardial performance was better preserved in CsA group. Mitochondrial outer membrane integrity was preserved, with less cytosolic diffusion of cytochrome C (p < 0.05) and less frequency of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling-positive myocytes in Ipo and CsA group (p < 0.05). Postconditioning prevented apoptosis-related mitochondrial permeabilization and dysfunction after cardioplegic arrest. Cyclosporine A postconditioning had a better effect than classic postconditioning in myocardial performance. ASAIO Journal 2011; 57: 197-202.