The Mechanism by Which Ischemic Postconditioning Reduces Reperfusion Arrhythmias in Rats Remains Elusive
The Mechanism by Which Ischemic Postconditioning Reduces Reperfusion Arrhythmias in Rats Remains Elusive
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DOI：
10.1177/1074248408329606
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发表时间：
2009-06-01
影响因子：
2.6
通讯作者：
Kloner, Robert A.
中科院分区：
文献类型：
--
作者：
Dow, Joan;Bhandari, Anil;Kloner, Robert A.
我们观察到，缺血后适应可显著降低再灌注诱导的室性心律失常，但其机制是否与先前描述的预适应或后适应减少梗死面积的途径有关尚不清楚。本研究的目的是确定是否已知的途径参与后处理对心律失常的保护作用。麻醉后的雌性大鼠进行5分钟的冠状动脉近端闭塞和5分钟的再灌注。他们要么不进行后训练，要么在最后再灌注前进行20秒再灌注和20秒再闭塞的4个循环（后训练）。全程监测心电图和血压。所谓的后适应激动剂和拮抗剂代表了一些机制进行了评估。与非后条件大鼠相比，给予线粒体通透性过渡孔抑制因子环孢素A治疗的非后条件大鼠未显示出再灌注诱导的室性心律失常的减少。Wortmannin （p13激酶抑制剂）、5 hydroxydecanoate（线粒体K-ATP通道选择性抑制剂）和8-巯基茶碱（腺苷受体阻滞剂）均不能阻断后处理后室性心动过速的降低。后适应降低再灌注引起的室性心律失常的机制可能独立于已知的与预适应和后适应的梗死保护作用有关的途径，包括腺苷、线粒体K-ATP通道、线粒体通透性过渡孔和p13-激酶- pakt途径。可能存在其他保护途径来解释后处理的抗心律失常作用。
We have observed that ischemic postconditioning markedly reduces reperfusion-induced ventricular arrhythmias, but whether the mechanism is related to previously described pathways of preconditioning or postconditioning for infarct size reduction is unknown. The purpose of this study was to determine whether known pathways were involved in postconditioning's protective effect on arrhythmias.Anesthetized female rats were subjected to 5 minutes of proximal coronary artery occlusion and 5 minutes of reperfusion. They were either not postconditioned or subjected to 4 cycles of 20 seconds reperfusion, 20 seconds reocclusion before final reperfusion (postconditioned). Electrocardiogram and blood pressure were monitored throughout. Alleged agonists and antagonists to postconditioning representing a number of mechanisms were evaluated.Nonpostconditioned rats treated with the Suppressor of the mitochondrial permeability transition pore, cyclosporine A, did not show a reduction in reperfusion-induced ventricular arrhythmias compared to control nonpostconditioned rats. Neither Wortmannin (p13-kinase inhibitor), 5 hydroxydecanoate (selective inhibitor of mitochondrial K-ATP channel), nor 8-sulfophenyl theophylline (blocker of adenosine receptors) blocked the reduction in ventricular tachycardia of postconditioning.The mechanism by which postconditioning reduces reperfusion-induced ventricular arrhythmias may he independent of known pathways that have been implicated in the infarct sparing effects of preconditioning and postconditioning-including adenosine, mitochondrial K-ATP channel, mitochondrial permeability transition pore, and p13-kinase-pAKt pathways. Alternative protective pathways may exist to explain the antiarrhythmic effect of postconditioning.