Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine.
OBJECTIVE
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 degeneration, 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).


CONCLUSIONS
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.
Liu
Jian-Xun
JX
Department of Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. jianxun@ht.rol.cn.net
Yu
Zhen
Z
Li
Xin-Zhi
XZ
Fu
Jian-Hua
JH
Shang
Xiao-Hong
XH
Yan
Ai-Guo
AG
Shi
Yue
Y
Ma
Yan-Lei
YL
D000284:Administration, Oral; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017023:Coronary Angiography; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology*; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000097:blood; D013552:Swine; D013556:Swine, Miniature
D002316:Cardiotonic Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D004110:Diltiazem