Abstract: AIM:To evaluate the effect of P5499,an inhibitor of AMPK,on cardioprotection induced by brief calcium depletion preconditioning.METHODS:Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion.Left ventricular pressure(LVP),left ventricular end-diastolic pressure(LVEDP),maximum rates of increase and decrease in left ventricular pressure(±dp/dtmax),heart rate(HR) and coronary flow(CF) were monitored.Left ventricular diastolic pressure(LVDP) and rate pressure product(RPP) were calculated to evaluate myocardial performance.Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium.RESULTS:In the hearts subjected to global ischemia-reperfusion(I/R group),levels of LVDP,±dp/dtmax,RPP and CF significantly decreased(P<0.01 vs.control group),and the infarct size was 39.6%±1.49%.Thirty-second perfusion with calcium-free KH solution(CPC group) before I/R reversed all the changes,level of LVEDP was decreased markedly(P<0.05 vs.I/R group),and levels of LVDP,±dp/dtmax,RPP,CF and infarct size were significantly improved(P<0.01 vs.I/R group).P5499 administered before ischemia had no apparent effect on I/R-induced injury but significantly attenuated the cardioprotection of calcium depletion preconditioning(P<0.01 vs.CPC group).CONCLUSION:AMPK may mediate the protective effect of calcium preconditioning against I/R-induced injury.