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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1239.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Development of an Animal Model for Spontaneous Myocardial Infarction (WHHLMI Rabbit)

Masashi Shiomi; Takashi Ito; Satoshi Yamada; Seinosuke Kawashima; Jianglin Fan

From the Institute for Experimental Animals (M.S., T.I., S.Y.), Kobe University School of Medicine, and Division of Cardiovascular and Respiratory Medicine (S.K.), Kobe University Graduate School of Medicine, Kobe, Japan, and Department of Pathology (J.F.), Institute of Basic Medical Science, University of Tsukuba, Tsukuba, Japan.

Correspondence to Masashi Shiomi, PhD, Institute for Experimental Animals, Kobe University School of Medicine, 7-5–1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail ieakusm{at}med.kobe-u.ac.jp

Objective— Coronary heart disease is the most common cause of death in developed countries. However, there are no suitable animal models that mimic spontaneous myocardial infarction in humans. In this study, we attempted to obtain a rabbit strain with spontaneous myocardial infarction by selective breeding of coronary atherosclerosis–prone Watanabe heritable hyperlipidemic (WHHL) rabbits, designated as WHHLMI rabbits.

Methods and Results— WHHLMI rabbits were characterized by the high incidence of fatal myocardial infarction at ages 11 to 35 months, being increased from 23% to 97% after the selective breeding. The ECG on WHHLMI rabbits showed a typical feature of myocardial infarction. Histological examination of hearts from suddenly deceased WHHLMI rabbits revealed old myocardial infarction accompanied by fresh myocardial lesions. The culprit coronary arteries exhibited severe atheromatous plaques (>90% lumen area stenosis), suggesting that coronary atherosclerosis is responsible for myocardial infarction observed in WHHLMI rabbits. In addition, the coronary plaques showed vulnerable features including macrophage-rich thin cap and large necrotic core.

Conclusions— To the best of our knowledge, this is the first report of spontaneous myocardial infarction in rabbits, and it is suggested that this WHHLMI rabbit strain will be a useful animal model to study human myocardial infarction.

Key Words: coronary atherosclerosis • myocardial infarction • vulnerable plaque • WHHLMI rabbit

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