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

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:halicarnasus
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Aim:To develop a new model of myocardial ischemia in Chinese miniature swineand reevaluate the cardioprotective effects of diltiazem.Methods:Myocardialischemia 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))wasorally administered to the swine by mixing into normal pig diet from 1 to 6 d afterself-embolus injection.The coronary angiography,30 point body surface electro-cardiogram(BS-ECG),hemodynamics,biochemistry,quantitative histology andpathohistology were determined 6 d after self-embolus injection.Results:Embo-lization occurred in the LAD coronary artery of the Chinese miniature swine in-jected by self-embolus.There were significant myocardial ischemia and largecardiac muscle infarction in the Chinese miniature swine,which were accompa-nied with increased BS-ECG,decreased hemodynamic indexes of the cardiac output,cardiac index,left cardiac work and left cardiac work index,and increased systemicvascular resistance index.Pathohistological analysis revealed myocardial degen-eration,necrosis,fibrosis,inflammatory cell infiltration and granulation tissuehyperblastosis(n=6).Diltiazem diminished the extent of the LAD embolism,ame-liorated myocardial ischemia,improved the hemodynamic indexes,increased theplasma superoxide dismutase activity,decreased the plasma malondialdehydecontent,narrowed the myocardial ischemic area and weakened the pathohistologicaldamage in the cardiac muscle(n=6).Conclusion:Myocardial ischemia induced byinjecting self-embolus into the LAD coronary artery in Chinese miniature swine isquite close to clinical pathophysiological conditions.Diltiazem is effective toinhibit 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: Myocardialischemia 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)) wasorally administered to the swine by mixing into normal pig diet from 1 to 6 d afterself-embolus injection.The coronary angiography, 30 point body surface electro-cardiogram (BS- ECG), hemodynamics, biochemistry, quantitative histology and pathology were determined 6 d after self-embolus injection. Results: Embo-lization occurred in the LAD coronary artery of the Chinese miniature swine in-jected by self-embolus. There were significant myocardial ischemia and largecardiac muscle infarction in the Chinese miniature swine, which were accompa-nied with increased BS-ECG, decreased hemodynamic indexes of the cardiac output, cardiac index, left cardiac work and left cardiac work index, and incr eased systemicvascular resistance index. Pathohistological analysis revealed myocardial degen-eration, necrosis, fibrosis, inflammatory cell infiltration and granulation tissuehyperblastosis (n = 6). Diltiazem diminished the extent of the LAD embolism, ame-liorated myocardial ischemia, improved the hemodynamic indexes, increased theplasma superoxide dismutase activity, decreased the plasma malondialdehydecontent, narrowed the myocardial ischemic area and weakened the pathohistologicaldamage in the cardiac muscle (n = 6) .Conlusion: Myocardial ischemia induced byinjecting self-embolus into the LAD coronary artery in Chinese miniature swine isquite close to clinical pathophysiological conditions. Diltiazem is effective to inhibit the myocardial ischemia and restore the heart function in this novel model.
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