Schulman D, Latchman D S, Yellon D M
Hatter Institute for Cardiovascular Studies, University College London Hospital and Medical School, WC1E 6DB, United Kingdom.
Am J Physiol Heart Circ Physiol. 2001 Oct;281(4):H1630-6. doi: 10.1152/ajpheart.2001.281.4.H1630.
Ischemic preconditioning (IP) reduces infarct size in young animals; however, its impact on aging is underinvestigated. The effect of variations in IP stimuli was studied in young, middle-aged, and aged rat hearts. Isolated hearts underwent 35 min of regional ischemia and 120 min of reperfusion. Hearts with IP were subjected to either one ischemia-reperfusion cycle (5 min of ischemia and 5 min of reperfusion per cycle) or three successive cycles before 35 min of regional ischemia. Additional studies investigated the effects of pharmacological preconditioning in aged hearts using the adenosine A(1) receptor agonist 2-chloro-N(6)-cyclopentyladenosine, the protein kinase C analog 1,2-dioctanoyl-sn-glycerol, and the mitochondrial ATP-sensitive potassium (K(ATP))-channel opener diazoxide. Infarct sizes indicated that the aged rat heart could not be preconditioned via ischemic or pharmacological means. The middle-aged rat heart had a blunted IP response compared with the young adult (only an increased IP stimulus caused a significant reduction in infarct size). These results suggest that there are defects within the IP signaling cascade of the aged heart. Clinical relevance is important if we are to use any IP-like mimetics to the benefit of an aging population.
缺血预处理（IP）可减小幼龄动物的梗死面积；然而，其对衰老的影响研究不足。在幼龄、中年和老年大鼠心脏中研究了IP刺激变化的影响。离体心脏经历35分钟的局部缺血和120分钟的再灌注。接受IP处理的心脏在35分钟局部缺血前，经历一个缺血-再灌注循环（每个循环5分钟缺血和5分钟再灌注）或三个连续循环。额外的研究使用腺苷A(1)受体激动剂2-氯-N(6)-环戊基腺苷、蛋白激酶C类似物1,2-二辛酰基-sn-甘油和线粒体ATP敏感性钾（K(ATP)）通道开放剂二氮嗪，研究了老年心脏中药理学预处理的效果。梗死面积表明老年大鼠心脏不能通过缺血或药理学手段进行预处理。与年轻成年大鼠相比，中年大鼠心脏的IP反应减弱（只有增加IP刺激才会导致梗死面积显著减小）。这些结果表明老年心脏的IP信号级联存在缺陷。如果我们要使用任何类似IP的模拟物来造福老年人群，临床相关性很重要。
