A Research About Opening Of Mitochondrial KATP Channel Induces Cardioprotective Effect On Ischemia-reperfusion Myocardium

[Objective] To evaluate the early and the delayed protection of diazoxide ( a mitochondrial ATP-sensitive potassium channel opener ) on myocardial ischemia- reperfusion injury the effects of ischemia-reperfusion on hemodynamics , electrophysiologic basis,myocardial ultrastructure, myocardial infarct size and cardiomyocytic apoptosis were observed in ameasthetized rabbit myocardium. [Method] 72 rabbits were devided into six groups :(1) control (C), (2) ischemia-reperfusion (IR), (3) diazoxide early protection (DEP) [diazoxide (3mg/kg) was administered 30 min before 1R ], (4) glibenclamide (G, a KATP channel blocker)+DEP[G(0.3 mg/kg) was administered 10 min before DEP], (5) 5-hydroxydecanoate (5-HD, a mitoK(ATP) channel blocker)+ DEP[5-HD(5 mg/kg) was administered 10 min before DEP] (6) diazoxide delayed protection(DDP) [diazoxide (3 mg/kg) was administered 24 hour before IR ]. (1)Compared with C group, the myocardial ultrastructure, sinus CK and infaret size of IR, DEP, 5-HD+DEP, G+DEP, DDP groups were analyzed. (2)With the programmed ectopic stimulation the effective refractory period(ERP) and dispersion of refratoriness in ischemic and normal myocardium was examined before ischemia and at 15min, I15min, ISOmin, R5min, RSOmin, RGOmin, R120min, (3)Heart rate , blood pressure and eletrocardiogram were analyzed at the same time. (4)Apoptosis rate of the ischemic from all groups were detected by TdT-mediated fluorescein-dUTP nick end labeling (TUNEL). [Results] (1) Compared with IR group DEP and DDP have little effect on hemodynamics. (2)DEP and DDP alleviated the myocardial ultrustructural injury produced by ischemia-reperfusion. (2)infarct size of IR group was 58.65?.51%, DEP limited it to about 27.09+3.24%,while DDP limited it to about 31.71+2.74 %(P<0. 01). (3)The level of CK in the sinus of DEP and DDP group was lower than that of IR(P<0.01). (4)DEP and DDP clearly reduced the appearance of life threatening ventricular arrhythmias' during ischemia-reperfusion(P<0. 01). (4)The trend of alteration of ERP in ischemic myocareium of DEP and DDP group was similar to t iat of IR group , but the dispersion of refratoriness was less than that of IR(P<0. u5 ). (6) myocardium apoptosis was also significantly decreased by DEP (14.47 + 3.42%) and DDP(16.50+3.69%) as compared with IR (24.25+4.34%). (7) The beneficial effects of DEP were abolished by 5-hydroxydecanoate and glibenclamide.[Conclusion] (l)DEP and DDP could alleviate the injury of ischemic myocardium andreduce the myocardial infaret size. (2)DEP and DDP could lessen the dispersion ofERP during the period of ische'mia and the early reperfusion, and reduce theappearance of ventricular arrhythmias;(3)DEP and DDP decreases cardiomyocyticapoptpsis induced by myocardial ischemia-reperfusion. (4) 5-hydroxydecanoate andglibenclamide reversed the cardioprotective effects of DEP and DDP . This"suggeststhat opening of mitoK(ATP) channels before ischemia is important for enhancementof myocardial tolerance against IR.