['In this study, experiments were designed to determine which parts and how carvedilol provided protection of the failed hearts under cardioplegia-induced hypoxia/reperfusion (H/R) insult.', 'Carvedilol could improve the perioperative and postoperative prognosis of the heart failure patients. The mechanism of carvedilol in prevention of the occurrence of cardiomyocytic apoptosis and preservation of cardiac function had been rarely studied.', 'Fifty Sprague-Dawley rats treated with placebo or daily carvedilol after coronary artery ligation were divided into five groups (ligation only-group 2; ligation followed with cardioplegia-induced cardiac arrest-group 3; daily oral carvedilol treatment at 0.1, 1.0, or 10.0 mg/kg after ligation followed with cardioplegia-induced cardiac arrest-groups 4, 5, and 6), whereas another 10 animals received sham operation only (group 1), 30 days before ex vivo H/R injury. Failed hearts were harvested and received 1-h cardiac hypoxia with intermittent cold cardioplegia infusion and followed by 2-h reperfusion with warm oxygenated phosphate-buffered saline solution using a Langendorff apparatus. Perfusate was sampled at various time points. After H/R injury, the myocardium was carefully dissected into infarct, peri-infarct, and remote zones, which were used for further studies. In vitro H/R studies were carried on HL-1 cardiomyocytes to further explore the possible downstream pathways.', 'Carvedilol could reduce the H/R-induced cardiomyocytic apoptosis and related proteins expression, especially in the peri-infarct zone, in a dose-dependent pattern. Carvedilol could also preserve cardiac contractility via modulation of the tumor necrosis factor α and interleukin 8 mRNA expression and reduction of Bcl-2 and cytochrome c protein production and decrease the occurrence of apoptosis ex vivo. In vitro experiments revealed that carvedilol exerted its antiapoptotic effect by way of phosphatidylinositol 3-kinase and MEK (mitogen-activated protein-kinase kinase), instead of protein kinase A, pathways.'] Does carvedilol treatment after myocardial infarct decrease cardiomyocytic apoptosis in the peri-infarct zone during cardioplegia-induced cardiac arrest?