No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits.
No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits.
复制标题
中老年兔缺血预适应的体内功效没有损失。
DOI：
10.1016/s0735-1097(01)01603-5
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发表时间：
2001
影响因子：
24
通讯作者：
Whittaker,P
中科院分区：
文献类型：
--
作者：
Przyklenk,K;Li,G;Whittaker,P
目的：我们验证了缺血预处理（PC）对心脏的保护作用在心脏衰老过程中丧失的假设。背景：尽管在几乎所有的模型中都有使用PC减少梗死面积的记录，但这一范式的一个例外是心脏老化，这一人群中心脏保护是最相关的。然而，在急性心肌梗死的体内模型中，没有先前的研究评估过年龄相关的PC疗效损失的概念，在该模型中，心血管衰老的明确标志被证明，梗死面积的减少是PC的“金标准”，是主要终点。方法采用兔体内模型，研究3组动物：成年（4 ~ 6个月）、中年（~ 2岁）和老年（~ 4岁）兔。在每个队列中，我们评估：1)对照组和PC组的梗死面积（通过四氮唑染色测量并以危险心肌百分比表示）；2)心血管衰老的形态学和功能特征（进行性心肌细胞肥大，心肌纤维化增加，对β -肾上腺素能刺激的反应减弱）。结果在成年动物中，PC组梗死面积明显小于对照组（29±4%∶57±2%;p < 0.01）。尽管中老年家兔表现出心血管老化的所有三个原型指标，但在两个队列中，PC明显减少了梗死面积（~ 50%）。结论：这些数据提供了第一个体内证据，表明PC患者的梗死面积减少本身并不受心血管年龄增加的影响。
OBJECTIVESWe tested the hypothesis that cardioprotection with ischemic preconditioning (PC) is lost in the aging, or senescent, heart.BACKGROUNDAlthough infarct size reduction with PC has been documented in virtually all models, a purported exception to this paradigm is the aging heart, the population in which cardioprotection is most relevant. However, no previous studies have assessed the concept of an age-associated loss in the efficacy of PC in an in vivo model of acute myocardial infarction in which definitive hallmarks of cardiovascular aging were demonstrated and a reduction of infarct size, the “gold standard” of PC, served as the primary end point.METHODSUsing the in vivo rabbit model, three cohorts of animals were studied: adult (4 to 6 months old), middle-aged (∼2 years old) and old (∼4 years old) rabbits. Within each cohort we assessed: 1) infarct size (measured by tetrazolium staining and expressed as percent myocardium at risk) in control and PC groups; and 2) morphologic and functional hallmarks of cardiovascular aging (progressive myocyte hypertrophy, increased myocardial fibrosis and attenuated responsiveness to beta-adrenergic stimulation).RESULTSIn adult animals, infarct size was significantly smaller in the PC group than in the control group (29 ± 4% vs. 57 ± 2%; p < 0.01). Although middle-aged and old rabbits exhibited all three archetypal indexes of cardiovascular aging, a comparable (∼50%) reduction in infarct size with PC was evident in both cohorts.CONCLUSIONSThese data provide the first in vivo evidence that infarct size reduction with PC is not precluded by increased cardiovascular age, per se.