Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine  

作　　者：Jian-xun LIU Zhen YU Xin-zhi LI Jian-hua FU Xiao-hong SHANG Ai-guo YAN Yue SHI Yan-lei MA 

机构地区：[1]Department of Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China

出　　处：《Acta Pharmacologica Sinica》2007年第1期52-57,共6页中国药理学报（英文版）

基　　金：Project supported by the National High Technology Research and Development Program of China(863 Program,No 2002AA2Z346B).

摘　　要：Aim： To develop a new model of myocardial ischemia in Chinese miniature swine and reevaluate the cardioprotective effects of diltiazem. Methods： Myocardial ischemia was induced by injecting self-embolus into the left anterior descending （LAD） coronary artery in qualified miniature swine. Diltiazem （5 mg·kg^-1·d^-1） was orally administered to the swine by mixing into normal pig diet from 1 to 6 d after self-embolus injection. The coronary angiography, 30 point body surface electrocardiogram （BS-ECG）, hemodynamics, biochemistry, quantitative histology and pathohistology were determined 6 d after self-embolus injection. Results： Embolization occurred in the LAD coronary artery of the Chinese miniature swine injected by self-embolus. There were significant myocardial ischemia and large cardiac muscle infarction in the Chinese miniature swine, which were accompanied with increased BS-ECG, decreased hemodynamic indexes of the cardiac output, cardiac index, left cardiac work and left cardiac work index, and increased systemic vascular resistance index. Pathohistological analysis revealed myocardial degen- eration, necrosis, fibrosis, inflammatory cell infiltration and granulation tissue hyperblastosis （n=6）. Diltiazem diminished the extent of the LAD embolism, ameliorated myocardial ischemia, improved the hemodynamic indexes, increased the plasma superoxide dismutase activity, decreased the plasma malondialdehyde content, narrowed the myocardial ischemic area and weakened the pathohistological damage in the cardiac muscle （n=6）. Conclusion： Myocardial ischemia induced by injecting self-embolus into the LAD coronary artery in Chinese miniature swine is quite close to clinical pathophysiological conditions. Diltiazem is effective to inhibit the myocardial ischemia and restore the heart function in this novel model.Aim： To develop a new model of myocardial ischemia in Chinese miniature swine and reevaluate the cardioprotective effects of diltiazem. Methods： Myocardial ischemia was induced by injecting self-embolus into the left anterior descending （LAD） coronary artery in qualified miniature swine. Diltiazem （5 mg·kg^-1·d^-1） was orally administered to the swine by mixing into normal pig diet from 1 to 6 d after self-embolus injection. The coronary angiography, 30 point body surface electrocardiogram （BS-ECG）, hemodynamics, biochemistry, quantitative histology and pathohistology were determined 6 d after self-embolus injection. Results： Embolization occurred in the LAD coronary artery of the Chinese miniature swine injected by self-embolus. There were significant myocardial ischemia and large cardiac muscle infarction in the Chinese miniature swine, which were accompanied with increased BS-ECG, decreased hemodynamic indexes of the cardiac output, cardiac index, left cardiac work and left cardiac work index, and increased systemic vascular resistance index. Pathohistological analysis revealed myocardial degen- eration, necrosis, fibrosis, inflammatory cell infiltration and granulation tissue hyperblastosis （n=6）. Diltiazem diminished the extent of the LAD embolism, ameliorated myocardial ischemia, improved the hemodynamic indexes, increased the plasma superoxide dismutase activity, decreased the plasma malondialdehyde content, narrowed the myocardial ischemic area and weakened the pathohistological damage in the cardiac muscle （n=6）. Conclusion： Myocardial ischemia induced by injecting self-embolus into the LAD coronary artery in Chinese miniature swine is quite close to clinical pathophysiological conditions. Diltiazem is effective to inhibit the myocardial ischemia and restore the heart function in this novel model.

关 键 词：myocardial ischemia DILTIAZEM animalmodels Chinese miniature swine 

分 类 号：R542.2[医药卫生—心血管疾病]