We previously demonstrated in rats that noninvasive delayed limb ischemic preconditioning (LIPC) induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb per day for three days confers the same cardioprotective effect as local ischemic preconditioning of the heart, but the mechanism has not been studied in depth. The aim of this project was to test the hypothesis that delayed LIPC enhances myocardial antioxidative ability during
ischemia-reperfusion by a
mitochondrial K(ATP) channel (mito K(
ATP))-dependent mechanism. Rats were randomized to five groups:
ischemia-reperfusion (IR)-control group, myocardial ischemic preconditioning (
MIPC) group, LIPC group, IR-5HD group and LIPC-5HD group. The
MIPC group underwent local ischemic preconditioning induced by three cycles of 5-min occlusion and 5-min reperfusion of the left anterior descending coronary arteries. The LIPC and LIPC-5HD groups underwent LIPC induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb using a modified blood pressure aerocyst per day for three days. All rats were subjected to
myocardial ischemia-
reperfusion injury. The IR-5HD and LIPC-5HD groups received the mito K(
ATP) channel blocker
5-hydroxydecanoate Na (5-HD) before and during the
myocardial ischemia-
reperfusion injury. Compared with the IR-control group, both the LIPC and
MIPC groups showed an amelioration of ventricular
arrhythmia, reduced
myocardial infarct size, increased activities of total
superoxide dismutase, manganese-
superoxide dismutase (
Mn-SOD) and
glutathione peroxidase, increased expression of
Mn-SOD mRNA and decreased
xanthine oxidase activity and
malondialdehyde concentration. These beneficial effects of LIPC were prevented by 5-HD. In conclusion, delayed LIPC offers similar cardioprotection as local IPC. These results support the hypothesis that the activation of mito K(
ATP) channels enhances myocardial antioxidative ability during
ischemia-reperfusion, thereby contributing, at least in part, to the
anti-arrhythmic and anti-
infarct effects of delayed LIPC.