Effect of aging on efficacy of ischemic preconditioning

在Langendorff灌流的大鼠心脏上研究了Againg对功能恢复和代谢产物、再灌注诱导的心律失常以及对PC敏感性的影响。年轻的心（Y：12 W/S）或老年前期（P：50 W/S）大鼠行全脑缺血（GI）15、20或25 min，再灌注30 min。在来自Y或P的一些心脏中，GI之前是PC，具有三次5分钟的缺血发作和间歇灌注。在实验过程中监测左心室（LV）功能（LV压力，LV压力发展和舒张速率）和体表心电图。灌注方案完成后，冷冻心脏并提取用于代谢物测定。在常氧灌注期间或缺血结束时，Y组和P组的心功能和心肌能量代谢产物无差异，但左室恢复时出现压力、峰值正和峰值负dP/dts（Y的30-50%），和高能磷酸盐P组（占Y组的50-60%）在任何GI期后左室舒张末期压均显著高于Y组。P组的房颤发生率高于Y组（GI 20分钟后50%比12.5%）。PC可改善Y组的收缩功能恢复（30-50%）并减少再灌注心律失常，而P组则无明显改善作用。此外，PC可能会随着年龄的增长而变得不那么有效。

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.