Molecular indices of apoptosis after intermittent blood and crystalloid cardioplegia

Background-We investigated whether intermittent blood and crystalloid cardioplegia differentially affect myocardial apoptosis and apoptosis gene-related proteins. Methods and Results-Rabbit hearts were perfused with Krebs-Henseleit buffer on a Langendorff apparatus. Control hearts (n=6) were perfused for 120 minutes without cardioplegic ischemia. Hearts were arrested for 60 minutes with warm (37 degrees C) crystalloid cardioplegia (iW-CCP) (n = 8) or with warm blood cardioplegia (iW-BCP) (n = 8) administered intermittently. In cold (0 to 4 degrees C) groups, hearts were arrested for 60 minutes with cold crystalloid cardioplegia (iC-CCP; n=8) or with cold blood cardioplegia (iC-BCP; n=6) administered intermittently. The hearts were reperfused for 30 minutes with Krebs-Henseleit buffer. iC-BCP significantly preserved the recovery of left ventricular and microvascular function compared with the other 3 experimental groups. There were no significant differences in total protein levels of caspase 3, Bel-2, Bad, and Bax among the groups. iC-BCP significantly induced greater phosphorylation of Bad (5.6 +/- 0.8-fold) as compared with the other 3 groups (3.4 +/- 0.6-fold in iC-CCP, P < 0.05; 2.5 +/- 0.3 in iW-BCP, P < 0.05; and 1.4 +/- 0.2 in iW-CCP, P < 0.01). iC-BCP induced less caspase 3 activation and apoptosis than the other 3 groups. Conclusions-iC-BCP is superior to the other cardioplegic solutions in increasing the phosphorylation of Bad, inhibiting the activation of caspase 3, and preventing apoptosis. These effects of iC-BCP were associated with preserved left ventricular function and endothelium-dependent relaxation of coronary microvessels.