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

Aging reduces the cardioprotective effect of ischemic preconditioning in the rat heart
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DOI:
10.1006/jmcc.2000.1189
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发表时间:
2000-07-01
影响因子:
5
通讯作者:
Dobson, JG
Dobson, JG
中科院分区:
医学2区
文献类型:
--
作者:
Fenton, RA;Dickson, EW;Dobson, JG

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哺乳动物心脏的多个短暂的缺血期对较长时间的缺血引起的形态和功能损害具有保护作用。预适应对缺血后收缩功能障碍的保护作用已被报道随着成年心脏的老化而减弱,本研究旨在确定成年心肌的老化是否减少了缺血时预适应诱导的坏死的减轻。取3月龄和22月龄Fischer 344只大鼠的离体灌流心脏进行起搏和测量左心室内压,用三苯基四氮唑测定心肌坏死程度。在没有预适应的情况下,青年和老年成年心脏造成45min的全球缺血。心肌坏死率分别为53+/-6%和49+/-6%。再灌流90min时,年轻心脏收缩功能(+dp/dt(Max))较预适应前下降80%,老年心脏下降52%。两个5min缺血/5min再灌流循环可显著减少年轻心脏的坏死发展和增强再灌流收缩功能,而在老年心脏,预适应并不能显著减少坏死的发展或增强再灌流收缩功能。这些数据表明,衰老降低了预适应对缺血诱导的心肌坏死提供心脏保护的有效性。(C)2000年学术出版社。
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 he 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. (C) 2000 Academic Press.