Department of Anesthesiology, Zunyi Medical College, Zunyi, Guizhou 563003, China.
Chin Med J (Engl). 2011 Dec;124(24):4205-10.
Many studies have indicated that hyperpolarizing cardioplegia is responsible for myocardial preservation and researchers have suggested that the adenosine triphosphate-sensitive potassium channels (K(ATP)) were the end effectors of cardio-protection. But whether mitochondrial K(ATP) plays an important role in hyperpolarizing cardioplegia is not apparent. The present study investigated the effect of hyperpolarizing cardioplegia containing pinacidil (a nonselective K(ATP) opener) on ischemia/reperfusion injury in rat hearts, especially the role of mitochondrial K(ATP) in pinacidil hyperpolarizing cardioplegia.
Sprague-Dawley rat hearts were Langendorff-perfused for 20 minutes with Krebs-Henseleit buffer at 37°C before equilibration. Cardiac arrest was then induced in different treatments: there was no arrest and ischemia in the normal group, the control group were arrested by clamping the aorta, depolarizing caidioplegia (St. Thomas solution containing 16 mmol/L KCl) and hyperpolarizing cardioplegia groups used St. Thomas solution containing 0.05 mmol/L pinacidil and 5 mmol/L KCl to induce cardiac arrest in group hyperkalemic and group pinacidil, in group hyperkalemic + 5-hydroxydecanote (5HD) and Pinacidil + 5HD, 5HD (0.1 mmol/L) was added to the above two solutions to block mitochondria K(ATP) channels. Global ischemia was then administrated for 40 minutes at 37°C, followed by 30 minutes of reperfusion. At the end of equilibration and reperfusion, hemodynamics, ultrastructure, and mitochondrial function were measured.
In the control group, ischemia/reperfusion decreased the left ventricular developed pressure, heart rate, coronary flow, mitochondrial membrane potential, impaired mitochondrial respiratory function, increased reactive oxygen species and left ventricular end diastolic pressure. Damage to myocardial ultrastructure was also evident. Both depolarized arrest and especially hyperpolarized cardioplegia significantly reduced these lesions. 5HD partially blocked the beneficial effects of pinacidil cardioplegia but showing no effects on hyperkalemic arrest.
Pinacidil cardioplegia provides better cardioprotection with preservation of hemodynamics, ultrastructure, and mitochondrial function than traditional cardioplegia. The mitochondria K(ATP) channels may play an important role in the protection mechanism.
许多研究表明，超极化停搏液可保护心肌，研究人员提出三磷酸腺苷敏感钾通道（KATP）是心肌保护的终末效应器。但线粒体 KATP 在超极化停搏液中的作用尚不清楚。本研究探讨了含匹那地尔（非选择性 KATP 开放剂）的超极化停搏液对大鼠心脏缺血/再灌注损伤的影响，特别是线粒体 KATP 在匹那地尔超极化停搏液中的作用。
在 37°C 下用 Krebs-Henseleit 缓冲液平衡 20 分钟后，对 Sprague-Dawley 大鼠心脏进行 Langendorff 灌注。然后在不同处理下诱导心脏停搏：正常组无停搏和缺血，对照组夹闭主动脉，使用含 16 mmol/L KCl 的去极化停搏液，超极化停搏液组使用含 0.05 mmol/L 匹那地尔和 5 mmol/L KCl 的 St.Thomas 溶液诱导高钾血症组和匹那地尔组心脏停搏，在高钾血症+5-羟癸酸（5HD）和匹那地尔+5HD 组中，向上述两种溶液中加入 0.1 mmol/L 的 5HD 以阻断线粒体 KATP 通道。在 37°C 下进行 40 分钟的全缺血，然后再进行 30 分钟的再灌注。在平衡和再灌注结束时，测量血流动力学、超微结构和线粒体功能。
在对照组中，缺血/再灌注降低了左心室发展压、心率、冠脉流量、线粒体膜电位、损害线粒体呼吸功能、增加活性氧和左心室舒张末期压。心肌超微结构也受到损伤。去极化停搏和特别是超极化停搏都显著减轻了这些损伤。5HD 部分阻断了匹那地尔停搏液的有益作用，但对高钾停搏无影响。
与传统停搏液相比，匹那地尔停搏液提供了更好的心脏保护作用，保持了血流动力学、超微结构和线粒体功能。线粒体 KATP 通道可能在保护机制中发挥重要作用。
