Diazoxide Reduces Rabbits' Myocardial Ischemia-reperfusion Injury

Objective: To study the effects of diazoxide on myocardial infarct size, myocardial apoptosis and bcl-2,bax gene expressions during ischemia-reperfusion period in rabbits. Methods: Twenty-four rabbits were randomly divided into four groups (n=6), pseudo-operation group (Group P), ischemia-reperfusion group (Group IR), ischemic preconditioning group (Group IP) and diazoxide group (Group DP). Group IR, Group IP and Group DP were subjected to 40 minutes of left anterior descending coronary artery (LAD) occlusion and followed for 3 hours of reperfusion. In Group IP, the ischemic preconditioning was induced by three cycles of 5-minute ischemia/5-minute reperfusion prior to LAD occlusion. In Group DP, the rabbits were pretreated intravenously with diazoxide (3mg· kg^-1) 30 minutes prior to LAD occlusion. In the end of reperfusion, then-hearts were taken out to weigh the non-ischemic, ischemic, and infarcted myocardium so as to calculate the infarct size. Apoptotic myocardial cells were detected by TdT-mediated dUTP nick end labeling (TUNEL) and the expressions of bcl-2 and bax protein were measured by immunohistochemical technique in the myocardium of ischemic area at risk. Results: Infarct size of Group DP(34±4%) and Group IP(32±5%) were markedly less than Group IR(66± 8%, p<0.001). The percentage of apoptotic cells in Group DP(34± 5%) and Group IP(32±6%) were reduced markedly as compared with Group IR(56±8%, p<0.001). Gray level (GL, the more higher GL, the more decreasing expression) of bcl-2 in Group P, Group IR, Group IP and Group DP were 114.5±4.2, 135.2±5.8, 124.5 ± 5.1, 122.8±6.6 respectively. The expressions of bcl-2 in Group IP and Group DP were increased as compared with Group IR (p=0.003,0.001 respectively), but less than the Group P(p=0.005,0.016 respectively). The GL of bax in Group P, Group IR, Group IP and Group DP were 134.7±7.8,85.5±6.2,117.8 ± 5.8,115.7 ± 5.4 respectively. The expressions of bax in Group IP and Group DP were decreased as compared with Group IR(p<0.001,in both), but still higher than Group P (p<0.001,in both). In this study, diazoxide and ischemic preconditioning regulated the expressions of bcl-2 and bax in the similar way(p=0.606, 0.562,respectively). Conclusion: Diazoxide and ischemic preconditioning reduces the rabbits' myocardial infarct size, which was induced by ischemia-reperfusion injury, in the similar way. This effect appears to be in part via regulating the expressions of bcl-2 and bax gene to reduce the myocytes apoptosis.