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左-卡尼汀心停搏液对犬体外循环心肌的保护作用
引用本文:向道康,孙宗全,夏家红,杜心灵,刘小斌,陈新忠. 左-卡尼汀心停搏液对犬体外循环心肌的保护作用[J]. 中国药理学通报, 2007, 23(7): 945-948
作者姓名:向道康  孙宗全  夏家红  杜心灵  刘小斌  陈新忠
作者单位:1. 贵州省人民医院心外科,贵州,贵阳,550002
2. 华中科技大学附属协和医院心外科,湖北,武汉,430022
摘    要:目的研究左-卡尼汀(L-CN)心停搏液冠状动脉间断顺行灌注对犬体外循环(CPB)心肌的保护作用。方法20只♂健康成年杂种犬,随机分为实验组和对照组,每组n=10。实验组术中于4℃ST.Thomas Ⅱ心停搏液中按12g·L-1加入L-CN;对照组以等量生理盐水代替L-CN加入ST.Thomas Ⅱ号冷晶体液作为心停搏液,其它条件同治疗组。升主动脉每阻断30min灌注1次,共4次,末次灌注液中氯化钾浓度减半。结果①升主动脉阻断时,两组冠状静脉窦血清心肌肌钙蛋白I(cTnI)、肌酸激酶MB同工酶(CK-MB)水平,左心室心肌丙二醛(MDA)和三磷酸腺苷(ATP)含量以及超氧化物歧化酶(SOD)活性比较差异无统计学意义(P>0.05);升主动脉开放时,实验组cTnI、CK-MB和MDA均低于对照组(P<0.05或P<0.01),SOD和ATP则高于对照组(P<0.05)。②与对照组比较,实验组术毕心脏自动复跳率明显升高(P<0.01)。③Western blot法分析腺苷二磷酸-核糖多聚酶(PARP)的裂解情况,两组术毕心肌均有PARP完整的113ku被水解为89ku的片段,但实验组被水解的PARP完整片段明显少于对照组。结论L-CN心停搏液通过改善CPB心肌的能量代谢,降低心肌细胞毒性产物的生成,减少心肌细胞凋亡,从而达到较好的心肌保护作用。

关 键 词:体外循环  心肌保护  心停搏液  左-卡尼汀  
文章编号:1001-1978(2007)07-0945-04
修稿时间:2007-03-10

Myocardial protective effect of L-carnitine cardioplegia solution in canine undergoing cardiopulmonary bypass
XIANG Dao-kang,SUN Zong-quan,XIA Jia-hong,DU Xin-ling,LIU Xiao-bin,CHEN Xin-zhong. Myocardial protective effect of L-carnitine cardioplegia solution in canine undergoing cardiopulmonary bypass[J]. Chinese Pharmacological Bulletin, 2007, 23(7): 945-948
Authors:XIANG Dao-kang  SUN Zong-quan  XIA Jia-hong  DU Xin-ling  LIU Xiao-bin  CHEN Xin-zhong
Abstract:Aim To investigate the myocardial protective effect of L-Carnitine(L-CN) as cardiac arresting solution in the process of cardiopulmonary bypass(CPB) in canine. Methods Twenty healthy male mongrel canines,15~20 kg, were randomly allocated into two groups: L-CN group (n=10, 12 g/L L-carnitine was put into the 4 ℃ ST. Thomas Ⅱ cardioplegia) and control group (n=10, identical to the L-carnitine group except that normal saline was administered instead of L-carnitine),the other conditions were the same. The cardioplegia solutions were infused for the antegrade intermittent coronary perfusion when the ascending aorta was cross-clamped, and were perfused for 4 times in all and repeated every 30 min, but the concentrations of postassium chloride would be reduced by half in last perfusion. In addition, every individual canine was premedicated with morphine (5 mg IM), and was intubated with the cuffed endotracheal tube after administration of fentanyl (5~10μg·kg-1, Ⅳ) to induce the anesthesia. Afterwards, the sodium pentobarbital (30 mg·kg-1 Ⅳ injection) was given for the first time and repeated (5 mg·kg-1) on demand during the experiment. The femoral artery were catheterized for the blood pressure , the blood gas analysis and the blood electrolyte monitoring, and the femoral vein for the fluid administration. The nasopharyngeal temperature was monitored. In both groups, cardial tropnin I (cTnI) and creatine kinase MB isozyme (CK-MB) levels in coronary venous sinus serum were measured just before the ascending aorta was cross-clamped and after the cross-clamp was removed, and myocardial tissue from left heart ventricle was available for the examination of the contents of malondialdehyde (MDA), adenosine triphosphate(ATP), the activity of superoxide dismutase (SOD). The expression of poly-(adenosine-ribose) polymerase (PARP) protein in the myocardial tissues was also examined by Western blot analysis. Results The levels of cTnI and CK-MB in coronary venous sinus serum, and MDA in myocardial tissue were significantly lower in the test group than that in the control group after cross-clamp was removed (P<0.05 or P<0.01),but the contents of ATP and SOD in myocardial tissue was significantly higher in the test group than that in the control group (P<0.05). The postoperative cardiac auto-rebeating rate in the test group was significantly higher than that in the control group (P<0.01). Western blot analysis showed that the intact 113 ku PARP was degraded in both groups, but the increasing quantity of 89 ku cleavage product in L-CN group was significantly less than that in control group. Conclusion Antegrade coronary perfusion of L-CN as an ingredient of cardiac arresting solution in the process of operation improves energy metabolism of cardiomyocyte and shows good protective effect on myocardium.
Keywords:cardiopulmonary bypass  myocardial protection  cardioplegia solution  L-carnitine  canine
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