Protective effects of pinacidil hyperpolarizing cardioplegia on myocardial ischemia reperfusion injury by mitochondrial KATP channels  

作　　者：YU Tian FU Xiao-yun LIU Xing-kui YU Zhi-hao 

机构地区：[1]Department of Anesthesiology, Zunyi Medical College, Zunyi,Guizhou 563003, China

出　　处：《Chinese Medical Journal》2011年第24期4205-4210,共6页中华医学杂志（英文版）

基　　金：This project was supported by a grant from the National Natural Science Foundation of China （No. 30460132）.

摘　　要：Background Many studies have indicated that hyperpolarizing cardioplegia is responsible for myocardial preservation and researchers have suggested that the adenosine triphosphate-sensitive potassium channels （KATe） were the end effectors of cardio-protection. But whether mitochondrial KATe plays an important role in hyperpolarizing cardioplegia is not apparent. The present study investigated the effect of hyperpolarizing cardioplegia containing pinacidil （a nonselective KATe opener） on ischemia/repeffusion injury in rat hearts, especially the role of mitochondrial KATe in pinacidil hyperpolarizing cardioplegia. Methods Sprague-Dawley rat hearts were Langendorff-perfused for 20 minutes with Krebs-Henseleit buffer at 37℃ 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 KCI） and hyperpolarizing cardioplegia groups used St. Thomas solution containing 0.05 mmol/L pinacidil and 5 mmol/L KCI to induce cardiac arrest in group hyperkalemic and group pinacidil, in group hyperkalemic ＋ 5-hydroxydecanote （5HD） and Pinacidil ＋ 5HD, 5HD （0.1 retool/L） was added to the above two solutions to block mitochondria KATe channels. Global ischemia was then administrated for 40 minutes at 37℃, followed by 30 minutes of reperfusion. At the end of equilibration and reperfusion, hemodynamics, ultrastructure, and mitochondrial function were measured. Results 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 blockeBackground Many studies have indicated that hyperpolarizing cardioplegia is responsible for myocardial preservation and researchers have suggested that the adenosine triphosphate-sensitive potassium channels （KATe） were the end effectors of cardio-protection. But whether mitochondrial KATe plays an important role in hyperpolarizing cardioplegia is not apparent. The present study investigated the effect of hyperpolarizing cardioplegia containing pinacidil （a nonselective KATe opener） on ischemia/repeffusion injury in rat hearts, especially the role of mitochondrial KATe in pinacidil hyperpolarizing cardioplegia. Methods Sprague-Dawley rat hearts were Langendorff-perfused for 20 minutes with Krebs-Henseleit buffer at 37℃ 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 KCI） and hyperpolarizing cardioplegia groups used St. Thomas solution containing 0.05 mmol/L pinacidil and 5 mmol/L KCI to induce cardiac arrest in group hyperkalemic and group pinacidil, in group hyperkalemic ＋ 5-hydroxydecanote （5HD） and Pinacidil ＋ 5HD, 5HD （0.1 retool/L） was added to the above two solutions to block mitochondria KATe channels. Global ischemia was then administrated for 40 minutes at 37℃, followed by 30 minutes of reperfusion. At the end of equilibration and reperfusion, hemodynamics, ultrastructure, and mitochondrial function were measured. Results 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 blocke

关 键 词：cardioplegic solutions heart arrest PINACIDIL ischemia/reperfusion injury myocardial mitochondrial ultrastructure potassium channel blockers 

分 类 号：Q95-33[生物学—动物学] Q244