Cardioprotection Of Ischemic Postconditioning And ATP-postconditioning In Rabbits Is Associated With The Activation Of Adenosine Receptors

OBJECTIVE: Recent experimental studies indicate that application of short,repetitive ischemia only during the onset of reperfusion, i.e. postconditioning(Post-con), attenuates myocardial reperfusion injury. This study was designed toexamine if Adenosine Triphosphate (ATP) had the same cardioprotective effects whenadministered at the onset of reperfusion, and investigate the role of adenosinereceptors in the protection by Post-con. METHODS: Thirty anesthetized open-chestrabbits were subjected to 40 min ischemia of the left anterior descending artery(LAD)and 180 min reperfusion, and assigned to the following five groups: (1)Control:40min ischemia/180 min reperfusion only without other intervention; (2)Post-con: Atthe first three minutes of reperfusion, three cycles of 30s reperfusion/30s ischemiapreceded 180 min reperfusion; (3)ATP-Post: ATP (3mg/kg, i.v) was used for 20 minstarting 5 min before reperfusion; (4) Post + SPT: Besides the treatment of Post-con,the non-selective adenosine receptor antagonist 8-p-sulfophenyl theophylline (SPT,5.3mg/kg,i.v) was given for 20 min starting 5 min before reperfusion; (5)CON+SPT:Only SPT was given. Infarct size (TTC staining), the plasma CK-MB, superoxidedismutase(SOD), and lipid peroxidation product malondialdehyde (MDA) weremeasured at the end of ischemia. RESULTS: Myocardial infarct size was limited inPost-con(12.6±2.6%) and in ATP-Post (13.3±4.8%) compared to Control(17.9±3.5%,p＜0.05, respectively), consistent with CK-MB(218±47U/Lin Post-con, 252±37U/LinATP-Post vs CON 340±29U/L, p＜0.05, respectively). SPT alone had no effect oninfarct size(20.3±3.1% in CON+SPT vs 17.9±3.5% in CON, p=NS), however,Post+SPT abrogated the myocardial infarct size reduction in postconditioning(18.4±2.8% in Post+SPT vs 12.6±2.6% in Post-con, p＜0.05); MDA was lower andSOD higher in Post-con (3.9±0.7nmol/m, 234±29 U/ml)and ATP-Post(3.3±0.8 nmol/ml,218±35U/ml) than CON(4.9±0.6nmol/ml, 176±17U/ml, p＜0.05, respectively).Similarly, Post+SPT abolished these protective effects in postconditioning.CONCLUSIONS: Our results suggest that ATP can protect the heart from myocardialischemia/reperfusion injury when administered at the onset of repeffusion and is aseffective as mechanical postconditioning. The mechanism of postconditioning'sprotection may be associated with the activation of adenosine receptors. ATP inducedpostconditioning may have potential utility in coronary interventions, thrombolysis,coronary artery bypass grafting.