title: Vasospasm of atherosclerotic coronary arteries precipitates acute ischemic myocardial damage in myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits.
abstract: OBJECTIVE
  This study tested the hypothesis that vasospasm can trigger coronary plaque injury and acute ischemic myocardial damage.
  
  
  RESULTS
  Myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits received an intravenous bolus of ergonovine maleate (0.45 µmol/kg) during intravenous infusion of norepinephrine (12 nmol/kg per minute) to provoke coronary spasm in vivo. After this treatment, coronary angiography demonstrated vasospasm, and the ECG showed ischemic abnormalities (ST depression/elevation and T-wave inversion) in 77% of animals (23/30). These changes normalized after nitroglycerin injection. In rabbits that demonstrated these ECG findings for >20 minutes, echocardiograms showed left ventricular wall motion abnormality. Serum levels of heart-type fatty acid-binding protein, cardiac troponin-I, and myoglobin increased markedly 4 hours after spasm provocation. In coronary lesions of myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits with provoked coronary spasm, we observed intimal injury in 60.9% in the form of endothelial cell protrusions (39.1%), denudation (30.4%), and macrophage extravasation (56.5%). Plaque disruption with luminal thrombus, however, was only seen in 2 of 23 animals (8.7%), and mural microthrombus was rarely observed (4.3%).
  
  
  CONCLUSIONS
  These observations show that provocation of vasospasm in myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits associates with subsequent ischemic myocardial damage. Although treatment with spasmogens altered aspects of plaque morphology, for example, endothelial protrusion and macrophage emigration, thrombosis was rare in these animals with chronic atherosclerotic disease.
authors.affiliation: From the Institute for Experimental Animals (M.S., T. Kobayashi, S.Y., T. Koike, N.K., T. Ito), Division of Comparative Pathophysiology (M.S.), and Division of Cardiovascular Medicine (T. Ishida, K.H.), Kobe University Graduate School of Medicine, Kobe, Japan; Department of Radiology, Shiga University of Medical Science, Otsu, Japan (N.N., A.S., K.M.); and Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.L.).
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishida
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Norihisa
authors.initials: N
authors.lastname: Nitta
authors.forename: Akinaga
authors.initials: A
authors.lastname: Sonoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamada
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.forename: Nobue
authors.initials: N
authors.lastname: Kuniyoshi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Murata
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
mesh_terms: D054058:Acute Coronary Syndrome / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D003324:Coronary Artery Disease / Q000235:genetics / Q000503:physiopathology*; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004874:Ergonovine / Q000494:pharmacology; D006949:Hyperlipidemias / Q000235:genetics / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D010120:Oxytocics / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D010120:Oxytocics; D014662:Vasoconstrictor Agents; D004874:Ergonovine; D009638:Norepinephrine
keywords: cardiovascular diseases; coronary atherosclerosis; coronary vasospasm; ischemia, myocardium; models, animal