title: Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine.
abstract: 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.
authors.affiliation: Department of Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. jianxun@ht.rol.cn.net
authors.forename: Jian-Xun
authors.initials: JX
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.forename: Xin-Zhi
authors.initials: XZ
authors.lastname: Li
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Fu
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Shang
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Yan
authors.forename: Yue
authors.initials: Y
authors.lastname: Shi
authors.forename: Yan-Lei
authors.initials: YL
authors.lastname: Ma
mesh_terms: 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
chemical_list: D002316:Cardiotonic Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D004110:Diltiazem