Effects of diazoxide postconditioning on myocardial ischemia-reperfusion injury in isolated rat hearts

Objective To investigate the effects of diazoxide postconditioning on myocardial ischemiareperfusion （I/R） injury in isolated rat hearts. Methods Male SD rats weighing 250-300 g were anesthetized with intraperitoneal pentobarbital 40 mg/kg. Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 37 ℃. Sixty-four isolated rat hearts were randomized into 4 groups after 20 min of equilibration （n = 16 each）： group control （group C）, group I/R, group diazoxide postconditioning （group D） and group mito-KATP channel blocker 5-hydroxydecanoate （5-HD） ＋ diazoxide postconditioning （group 5-HD ＋ D）. Group C received continuous perfusion for another 70 min. In group I/R, D and 5-HD ＋ D, the hearts underwent 40 min of iscbemia followed by 30 min of reperfusion. 4 ℃ ST. Thomas cardioplegic solution was administered prior to ischemia in group I/R. Group D received 5 min of perfusion with K-H solution containing 50μ mol/L diazoxide at 5 min of reperfusion. Group 5-HD ＋ D received 5 min of perfusion with K-H solution containing 50 μmol/L 5-HD before reperfusion with diazoxide. Eight hearts were taken at the end of equilibration and reperfusion and the indexes of cardiac function were recorded. Then the mitochondria were extracted for determination of mitochondrial membrane potential （MMP）, reactive oxygen species （ROS） release, and respiratory function indexes. Results Compared with group C, MMP was significantly decreased, ROS release was significantly increased, mitochondrial respiratory function and cardiac function declined at the end of reperfusion in the other three groups （ P 〈 0.05 or 0.01 ）. MMP was significantly increased, ROS release was significantly decreased, mitochondrial respiratory function and cardiac function were improved in group D compared with group I/R and 5-HD ＋ D.Conclusion Diazoxide postconditioning can reduce myocardial I/R injury in rats via the opening of mito-KATPchannels and improving the mitochondrial function. Key words: Diazoxide;  Myocardial reperfusion injury;  Postconditioning