Aging reduces the cardioprotective effect of ischemic preconditioning in the rat heart

Abstract

Multiple brief periods of ischemia in the mammalian heart elicits protection against morphologic and functional damage caused by longer-duration ischemia. Preconditioning-induced protection against post-ischemic contractile dysfunction has been reported to be depressed with aging of the adult heart. This study was undertaken to determine whether aging of the adult myocardium reduces the preconditioning-induced attenuation of necrosis observed with ischemia. Isolated, perfused hearts obtained from Fischer 344 rats of either 3 (young) or 22 (aged) months of age were paced and instrumented for determination of developed left ventricular pressure. Necrosis was determined with triphenyltetrazolium. In the absence of preconditioning, young and aged adult hearts made globally ischemic for 45 min developed necrosis involving 53+/-6% and 49+/-6% of the myocardium, respectively. Contractile function (+dP/dt(max)) at 90 min of reperfusion was depressed by 80% in young and 52% in aged hearts, compared to values obtained prior to preconditioning. Preconditioning with two 5 min ischemia/5 min reperfusion cycles significantly reduced necrosis development and enhanced reperfusion contractile function in young hearts. However, in aged adult hearts, the preconditioning did not significantly reduce the development of necrosis or enhance reperfusion contractile function. These data suggest that aging reduces the effectiveness of preconditioning in providing cardioprotection against ischemic-induced myocardial necrosis.