Yeh Chi-Hsiao, Wang Yao-Chang, Wu Yi-Cheng, Chu Jaw-Ji, Lin Pyng Jing
Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
Chest. 2003 May;123(5):1647-54. doi: 10.1378/chest.123.5.1647.
In modern cardiac surgery, crystalloid or blood cardioplegic solutions have been used widely for myocardial protection; however, ischemia does occur during protection with intermittent infusion of cold crystalloid or blood cardioplegic solutions. The present study was designed to evaluate the effect of different cardioplegic methods on myocardial apoptosis and coronary endothelial injury after global ischemia, cardiopulmonary bypass (CPB), and reperfusion in anesthetized open-chest dogs.
The dogs were classified into five groups to identify the injury of myocardium and coronary endothelium: group 1, normothermic CPB without cardiac arrest; group 2, hypothermic CPB with continuous tepid blood cardioplegia, and with cardiac arrest; group 3, hypothermic CPB with intermittent cold blood cardioplegia, and with cardiac arrest; group 4, hypothermic CPB with intermittent cold crystalloid cardioplegia, and with cardiac arrest; and group 5, sham-operated control group. During CPB, cardiac arrest was achieved with different cardioplegia solutions for 60 min, followed by reperfusion for 4 h before the myocardium and coronary arteries were harvested. Coronary arteries were harvested immediately and analyzed by scanning electron microscopy. Cardiomyocytic apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Western blot, and DNA ladder methods.
Regardless of the detection method used, significantly higher percentages of apoptotic cardiomyocytes were found in group 3 and group 4 than in other groups. Expression of caspase-3 correlated with increased apoptosis. Scanning electron microscopy revealed severe endothelial injury of coronary arteries in group 3 and group 4.
These results point to an important explanation for the difference in cardiac recovery after hypothermic ischemia and arrest with various cardioplegic solutions.
在现代心脏外科手术中,晶体或血液心脏停搏液已被广泛用于心肌保护;然而,在间歇性输注冷晶体或血液心脏停搏液进行保护期间,心肌缺血仍会发生。本研究旨在评估不同心脏停搏方法对麻醉开胸犬在全心缺血、体外循环(CPB)及再灌注后心肌细胞凋亡和冠状动脉内皮损伤的影响。
将犬分为五组以确定心肌和冠状动脉内皮的损伤情况:第1组,常温CPB不停跳;第2组,低温CPB持续温血心脏停搏,心脏停跳;第3组,低温CPB间歇性冷血心脏停搏,心脏停跳;第4组,低温CPB间歇性冷晶体心脏停搏,心脏停跳;第5组,假手术对照组。在CPB期间,用不同的心脏停搏液使心脏停跳60分钟,然后再灌注4小时,之后采集心肌和冠状动脉。立即采集冠状动脉并通过扫描电子显微镜进行分析。使用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记法、蛋白质免疫印迹法和DNA梯状条带法检测心肌细胞凋亡。
无论采用何种检测方法,第3组和第4组中凋亡心肌细胞的百分比均显著高于其他组。半胱天冬酶-3的表达与凋亡增加相关。扫描电子显微镜显示第3组和第4组冠状动脉内皮严重损伤。
这些结果为低温缺血及使用各种心脏停搏液停跳后心脏恢复存在差异提供了重要解释。