The Effect Of Closing Of Mitochondrial Permeability Transition Pore On Immature Rabbit Heart Protection

ObjectiveTo observe the cardioprotective effect of hyperkalemic cardioplegic solution enriched with either mitochondrial permeability transition pore inhibitor or potassium channel openers on rabbit immature heart subjected ischemia.Materials and Methodsforty-five immature rabbit hearts were randomly divided into 5 groups.After control perfusion in modified Langendorff mode with Krebs-Henseleit bicarbonate buffer for 20 minutes,the isolated immature rabbit hearts were infused with different cardioplegia 20 ml.During global ischemia,cardioplegia was reinfused every 30 minutes and hearts were preserved in 36±1℃.After one hours' global ischemia,the hearts were reperfused with Krebs-Henseleit bicarbonate buffer for 60 minutes.The different cardioplegia include St.Thomas(10 rabbits);St.Thomas+30μmol/L diazoxide(8 rabbits);St.Thomas+0.2μmol/L cyclosporin A(10 rabbits):St.Thomas+30μmol/L diazoxide+20μmol/L atractyloside(8 rabbits);St.Thomas+30μmol/L diazoxide+100μmol/L 5-hydroxydecanoic acid(9 rabbits).In groups of St.Thomas+cyclosporin and St.Thomas+ diazoxide+ atractyloside,the hearts were reperfused with Krebs-Henseleit bicarbonate buffer enriched with 0.2μmol/L cyclosporin A or 20μmol/L atractyloside for 10 minutes first,and then reperfused with Krebs-Henseleit bicarbonate buffer for 50 minutes.The hemodynamic parameters and coronary flow were measured before ischemia and during reperfusion.Results1.Compared to the St.Thomas group,postischemic recorery of LVDP was better in St.Thomas+ diazoxide group and St.Thomas+ cyclosporin A group(P＜0.05). Compared to the St.Thomas+ diazoxide group,postischemic recorery of LVDP was worse in St.Thomas+ diazoxide+ atractyloside group and St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group(P＜0.05).Compared to the St.Thomas+ cyclosporin A group,postischemic recorery of LVDP was worse in St.Thomas+ diazoxide+ atractyloside group and St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group(P＜0.05).2.Compared to the St.Thomas group,postischemic recorery of LVMP was better in St.Thomas+ diazoxide group and St.Thomas+ cyclosporin A group(P＜0.05)and worse in St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group at 5 minute(P＜0.05).Compared to the St.Thomas+ diazoxide group,postischemic recorery of LVMP was worse in St.Thomas+ diazoxide+ atractyloside group and St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group(P＜0.05).Compared to the St.Thomas+ cyclosporin A group,postischemic recorery of LVMP was worse in St.Thomas+ diazoxide+ atractyloside group and St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group(P＜0.05). 3.Compared to the St.Thomas group,postischemic recorery of CF was better in St.Thomas+ diazoxide group at(P＜0.05)and worse in St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group at 50minute and 60minute(P＜0.05).Compared to the St.Thomas+diazoxide group,postischemic recorery of CF was worse in St.Thomas+diazoxide+atractyloside group and St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group(P＜0.05).Compared to the St.Thomas+ cyclosporin A group,postischemic recorery of CF was worse in St.Thomas+ diazoxide+ atractyloside group and St.Thomas+ diazoxide+ 5-hydroxydecanoic acid group(P＜0.05).ConclusionBoth potassium channel openers diazoxide and mitochondrial permeability transition pore inhibitor cyclosporin A can significantly improve the myocardial protection on immature rabbit hearts.And the myocardial protection of potassium channel openers maybe go through closing mitochondrial permeability transition pore to achieve.