Myocardial Protection By Ischemic Preconditioning In Skeletal Muscle And The Role Of ATP-Sensitive Potassium Channel In Rabbits

BackgroundMyocardial preconditioning is an endogenous protective mechanism in which brief period of myocardial ischemia and reperfusion render the myocardium resistant to a subsequent more sustained ischemic insult.This phenomenon has been confirmed hi a variety of animals and in human beings.Ischemic precondition does not only exist in myocardium,but also in other organs such as kidney,skeletal muscle,brain and liver. It has been confirmed that myocardial protection can be achieved by ischemic preconditioning in remote noncardiac tissue.Many studies make a conclusion that ATP-sensitive potassium (KATP) channel invole in ischemic preconditioning. Whether the cardioprotective effect of ischemic preconditioning in remote noncardiac tissue is associated with KATP channel,the studies about this were rarely reported. ObjectivesThis study intend to investigate whether ischemia of skeletal muscle can induce myocardial ischemic preconditioning and whether the effect of cardioprotection is mediated by KATP channel. MethodsForty male white rabbits were randomly divided into five groups and each group included eight animals.There were control group,classic ischemic preconditioning(IP) group,ischemic preconditioning hi skeletal muscle(MIP) group,MEP plus glibenclamide(MIP+Gli) group and glibenclamide(Gli) group.All animals underwent thoracotomy and hearts were quickly excised and mounted on a modified Langendorff apparatus.Isolated hearts were perfused retrogradely with Krebs-Henseleit buffer and underwent 45-min of global ischemia and 2-h reperfusion.Hearts hi the IP groups experienced two cycles of 5-min ischemia and 10-min reperfusion prior to sustained ischemiaSkeletal muscle of rabbits hi the MIP group were pretreated in vivo with 15-min ischemia and 15-min reperfusion. Rabbits in the MIP+Gli group were given oral Glibenclamide 150-min before ischemia of skeletal muscle.Animals hi the Gli group were given Glibenclamide150-min before hearts were isolated.Necrotic zone in the left ventricle was determined by tetrazolium staining and expressed as percentage of weightlnfarct size was defined as the ratio of the weight of the necrotic zone to the left ventricle.Infarct areajeft ventricular end-diastolic pressure(LVEDP), left ventricular developed pressure(LVDP),coronary flow and ventricular arrhythmias were observed and compared with whole groups. ResultsInfarct size in the IP group and MIP group was 31+5% and 35+7% respectively,it was significant lower than that in the control group(56+5%)(p<0.05).Infarct size had no significant difference in the MIP+Gli group(53+7%) and Gli group(58+6%) compared with the control group(p>0.05).During reperfusion period,LVEDP in the IP group and MEP group was significant lower than that in the control group(p<0.05),LVDP was higher than that in the control group(p<0.05).The occurrence rate of ventricular arrhythmias in the IP group and MIP group was lower than that in the control group .however ,occurrence rate of ventricular fibrillation in the MIP group had no significant difference compared with the control group. During reperfusion period, there were no significant difference in LVEDPJLVDP and occurrence rate of arrhythmias among the MIP+Gli group,Gli group and the control group(pX).05). ConclusionsIschemia of skeletal muscle can precondition the myocardium and induce cardioprotection.KATP channel is involved in this mechanism.Glibenclamide (a selective inhibitor of KATP channel) can abonish this effect of protection.