Preconditioning does not prevent postischemic dysfunction in aging heart
Preconditioning does not prevent postischemic dysfunction in aging heart
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DOI：
10.1016/0735-1097(96)00070-8
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发表时间：
1996-06-01
影响因子：
24
通讯作者：
Rengo, F
中科院分区：
文献类型：
--
作者：
Abete, P;Ferrara, N;Rengo, F
目的。本研究旨在探讨在成年和老年离体灌注大鼠心脏中，单次或多次短暂缺血以及在较长时间缺血期之前和再灌注之后给予外源性去甲肾上腺素的影响。
背景。老年人冠状动脉疾病的死亡率更高。缺血预处理已被认为是一种内源性的对抗缺血 - 再灌注损伤的保护形式。然而，预处理在衰老心脏中的作用尚不清楚。
方法。我们比较了预处理短暂缺血和去甲肾上腺素刺激对成年（6个月大）和老年（24个月大）大鼠离体灌注心脏20分钟全心常温缺血和40分钟再灌注的保护作用。通过高效液相色谱法测定冠状动脉流出液中的去甲肾上腺素释放量。
结果。在成年心脏中，单次预处理短暂缺血和去甲肾上腺素刺激后，发展压百分比的最终恢复得到改善（分别为87.7±9%和82.3±8.7%），而未预处理的对照心脏为（50.6±4.8%，p < 0.01[均值±标准差]）。在老年心脏中，短暂缺血刺激后预处理对发展压恢复没有影响（39.8±4.9%对41.6±5.8%，p =无显著差异），但去甲肾上腺素刺激后有影响（74.3±10.5，p < 0.01）。成年心脏在预处理短暂缺血刺激后去甲肾上腺素释放显著增加，而老年心脏则没有（与成年相比，p < 0.01）。在成年和老年心脏中，α - 肾上腺素能受体拮抗剂均可阻断短暂缺血和去甲肾上腺素诱导的预处理。多次短暂缺血刺激能够减轻成年心脏的缺血后功能障碍，但对老年心脏无效。
结论。预处理短暂缺血刺激可显著减轻成年心脏的缺血后功能障碍，但对老年心脏无效，而外源性去甲肾上腺素在成年和老年心脏中均能模拟预处理。缺血预处理可使成年心脏的去甲肾上腺素释放增加，但老年心脏则没有。在成年和老年心脏中，α - 肾上腺素能受体阻断均可消除短暂缺血刺激和去甲肾上腺素诱导的预处理。因此，我们的数据表明，衰老心脏中不存在预处理，这可能与缺血预处理时去甲肾上腺素释放减少和α - 肾上腺素能受体刺激减弱有关。
Objectives. This study was performed to investigate the effect of single or multiple brief periods of ischemia and the administration of exogenous norepinephrine before a more prolonged ischemic period and after reperfusion in adult and senescent isolated and perfused rat hearts.Background. The mortality rate for coronary artery disease is greater in the elderly. Ischemic preconditioning has been proposed as an endogenous form of protection against ischemia-reperfusion injury. However, the role of preconditioning in aging heart is unknown.Methods. We compared the protective effect of preconditioning transient ischemic and norepinephrine stimuli against 20 min of global normothermic ischemia and 40 min of reperfusion in isolated perfused hearts of adult (6 months old) and senescent (24 months old) rats. Norepinephrine release in coronary effluent was determined by high performance liquid chromatography.Results. Final recovery of percent developed pressure was improved after single preconditioning transient ischemic and norepinephrine stimuli in adult hearts (87.7 +/- 9% and 82.3 +/- 8.7%) versus unconditioned control hearts (50.6 +/- 4.8%, p < 0.01 [mean +/- SD]). The effect of preconditioning on developed pressure recovery was not present in senescent hearts after transient ischemic stimulus (39.8 +/- 4.9% vs. 41.6 +/- 5.8%, p = NS) but was present after norepinephrine stimulus (74.3 +/- 10.5, p < 0.01), Norepinephrine release significantly increased after preconditioning transient ischemic stimulus in adult but not in senescent hearts (p < 0.01 vs. adult), Transient ischemic- and norepinephrine-induced preconditioning was blocked by alpha-adrenergic receptor antagonists in both adult and senescent hearts. Multiple transient ischemic stimuli were able to reduce postischemic dysfunction in adult but not in senescent hearts.Conclusions. Preconditioning transient ischemic stimulus significantly reduces postischemic dysfunction in adult but not in senescent hearts, whereas exogenous norepinephrine is able to mimic preconditioning in both adult and senescent hearts. Ischemic preconditioning induces an increase in norepinephrine release in adult but not in senescent hearts. Preconditioning induced by transient ischemic stimulus and norepinephrine was abolished by alpha-adrenergic receptor blockade in both adult and senescent hearts. Thus, our data demonstrate that preconditioning is absent in aging heart and is probably related to the reduction of norepinephrine release and alpha-adrenergic receptor stimulation in response to ischemic preconditioning.