PHARMACOLOGICAL EVIDENCE FOR THE PERSISTENT ACTIVATION OF ATP-SENSITIVE K+ CHANNELS IN EARLY PHASE OF REPERFUSION AND ITS PROTECTIVE ROLE AGAINST MYOCARDIAL STUNNING
PHARMACOLOGICAL EVIDENCE FOR THE PERSISTENT ACTIVATION OF ATP-SENSITIVE K+ CHANNELS IN EARLY PHASE OF REPERFUSION AND ITS PROTECTIVE ROLE AGAINST MYOCARDIAL STUNNING
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DOI：
10.1161/01.cir.92.8.2266
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发表时间：
1995-10-15
期刊：
影响因子：
37.8
通讯作者：
ARITA, M
中科院分区：
文献类型：
--
作者：
SHIGEMATSU, S;SATO, T;ARITA, M
研究背景心肌ATP敏感性钾通道的激活被认为是心肌缺血时的保护机制。然而，该通道在再灌注过程中的行为和作用仍不确定。方法和结果豚鼠右心室壁进行了研究，通过使用微电极和力传感器。通过冠状动脉以恒定流速灌注每种制剂，并以3 Hz刺激。在第一个方案中，使制备物经受10分钟的无血流缺血，随后是60分钟的再灌注。引入缺血使动作电位时程（APD）缩短至缺血前值的58.7 +/-3.1%，并伴有静息膜电位（12 +/-0.8 mV）和动作电位振幅（34.6 +/-1.8 mV）降低。再灌注时，APD虽恢复，但在再灌注30分钟内仍明显缩短。格列本脲（10 μ mol/L）可明显减轻缺血时APD的缩短，并促进再灌注后APD的恢复。当格列本脲从再灌注开始应用时，持续的APD缩短被显著抑制。在未处理的制剂中，缺血期间产生的张力降低，再灌注60分钟后恢复（达到缺血前值的92.0 +/-6.4%）。在缺血前或再灌注开始时应用格列本脲显著抑制收缩力的恢复（P
Background The activation of cardiac ATP-sensitive potassium channels is reported to protect myocardium during ischemia. However, the behavior and role of this channel during reperfusion remain uncertain.Methods and Results Guinea pig right ventricular walls were studied by use of microelectrodes and a force transducer. Each preparation was perfused via the coronary artery at a constant flow rate and was stimulated at 3 Hz. In the first protocol, the preparation was subjected to 10 minutes of no-flow ischemia, which was followed by 60 minutes of reperfusion. Introduction of ischemia shortened the action potential duration (APD) to 58.7+/-3.1% of the preischemic values, in association with a decrease in the resting membrane potential (by 12+/-0.8 mV) and action potential amplitude (by 34.6+/-1.8 mV). On reperfusion, although the APD was restored, it remained shortened for up to approximately 30 minutes of reperfusion, In the presence of glibenclamide (10 mu mol/L), the shortening of the APD during ischemia was significantly attenuated and the restoration of APD after reperfusion was significantly facili rated. When glibenclamide was applied from the onset of reperfusion, the persistent APD shortening was significantly suppressed. The developed tension decreased during ischemia and recovered after 60 minutes of reperfusion (up to 92.0+/-6.4% of preischemic values) in the untreated preparations. The application of glibenclamide that was started before ischemia or from the onset of reperfusion significantly suppressed the recovery of contractility (P