Effect of aging on efficacy of ischemic preconditioning

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The effects of againg on the recovry of function and metabolites, reperfusion-induced arrhytmias, and sensitivity to PC were investigated in Langendorff-perfused rat hearts. Hearts from young (Y : 12 W/S) or pre-senile (P : 50 W/S) rats were subjected to 15,20, or 25-min global ischemia (GI) followed by 30-min of reperfusion. In some hearts from Y or P,GI was preceded by PC with three 5-min episodes of ischemia with intermittent perfusion. Left ventricular (LV) function (LV pressures, rates of LV pressure development and relaxation) and surface electrocardiogram were monitored during experiments. After perfusion protocol was completed, hearts were frozen and extracted for metabolite assays. There were no differences in cardiac function and myocardial energy metabolites during normoxic perfusion or at the end of ischemia between Y and P.However, recoveries of LV developed pressure, peak positive and peak negative dP/dts (30-50% of Y), and high-energy phoshates (50-60% of Y) were poorer in P with marked increase in LV end-diastolic pressure after anyperiods of GI as compared with those in Y.The incidence of ventricular tachycardia/fibrillation was higher (50% vs.12.5% after 20-min of GI) in P than in Y.PC improved recovery of contractile function (30-50%) and reduced reperfusion arrhythmias in Y whereas no beneficial effects were obtained by the maneuver in P.The results demonstrated that myocardial sensitivity to ischemia-reperfusion injury increased with aging. Furthermore, PC might become less effective with aging.