ADENOSINE-A(1) RECEPTORS, K(ATP) CHANNELS, AND ISCHEMIC PRECONDITIONING IN DOGS
ADENOSINE-A(1) RECEPTORS, K(ATP) CHANNELS, AND ISCHEMIC PRECONDITIONING IN DOGS
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DOI：
10.1152/ajpheart.1993.264.5.h1327
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发表时间：
1993-05-01
影响因子：
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通讯作者：
GROSS, GJ
中科院分区：
文献类型：
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作者：
AUCHAMPACH, JA;GROSS, GJ
本研究的目的是表征腺苷在犬心脏心肌缺血预处理中的作用。与未进行预处理的狗相比，经过 5 分钟缺血预处理后，巴比妥麻醉犬在左回旋支冠状动脉闭塞 60 分钟和再灌注 5 小时后，梗塞面积显着减小（4.8 +/- 1.9 与 27.9 +/- 4.5%；P < 0.05）。用非选择性腺苷受体拮抗剂 PD 115199 或选择性腺苷 A1 受体拮抗剂 8-环戊基-1,3-二丙基黄嘌呤进行预处理可阻断这种保护作用，尽管在没有预处理的情况下，这两种拮抗剂都不影响梗塞面积。在延长 60 分钟的闭塞期之前，在 5 分钟内冠状动脉内输注两种不同剂量的腺苷或双嘧达莫并不能模拟预处理；然而，冠状动脉内输注腺苷和双嘧达莫的组合可显着减少梗塞面积（13.6 +/- 4.1%），但通过使用 ATP 依赖性钾 (K(ATP)) 通道拮抗剂格列本脲进行预处理可消除这种现象。这些结果表明，腺苷 A1 受体的激活通过打开 K(ATP) 通道在犬心脏中产生心肌预处理。
The objective of the present study was to characterize the role of adenosine in myocardial ischemic preconditioning in the canine heart. Preconditioning with 5 min of ischemia resulted in a marked reduction in infarct size after 60 min of left circumflex coronary artery occlusion and 5 h of reperfusion in barbital-anesthetized dogs compared with dogs that were not preconditioned (4.8 +/- 1.9 vs. 27.9 +/- 4.5%; P < 0.05). Pretreatment with either the nonselective adenosine receptor antagonist PD 115199 or the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked this protective effect, although in the absence of preconditioning neither of the antagonists affected infarct size. Intracoronary infusion of two different doses of adenosine or dipyridamole over a 5-min period before a prolonged 60-min occlusion period did not mimic preconditioning; however, intracoronary infusion of a combination of adenosine and dipyridamole produced a significant reduction in infarct size (13.6 +/- 4.1%), which was abolished by pretreatment with the ATP-dependent potassium (K(ATP)) channel antagonist glibenclamide. These results suggest that activation of adenosine A1 receptors produces myocardial preconditioning in the canine heart by opening K(ATP) channels.