抄録
Ischemic heart disease is important in developed countries. However, there are few suitable animal models for myocardial infarction. To develop myocardial infarction (MI) -prone WHHL rabbits, we have carried out selective breeding by using coronary atherosclerosis-prone WHHL rabbits in our colony since 1994. We used following indices for the selective breeding; 1) vulnerable coronary plaque, 2) severe coronary stenosis greater than the lumen area stenosis with the mean value plus the standard error value of the parents' generation, 3) plasma cholesterol levels above 800 mg/dl at 12 months old, and 4) occurrence of myocardial infarction. During the selective breeding, housing condition was maintained constant and rabbits were fed standard rabbit chaw. We did not treat rabbits especially except the selective breeding. At 1999, after the selective breeding, myocardial infarction was observed in 94% of rabbits deceased up to 35 months old. Age of 35 months old in rabbits corresponds to approximately 44 years old in human by calculation of their life span (75 years old in humans and 60 months old in experimen-tal rabbits) . In histological examination, many rabbits after the selective breeding showed findings of acute myocardial infarction alone or in combination with findings of old myocardial infarction. Myocardial lesions of MI-prone WHHL rabbits were observed mainly at the subendocardial region circumf erentially, and about 60% rabbits showed transmural infarction in combination with subendocardial infarction. In some MI-prone WHHL rabbits, the profile of the electrocardiogram showed typical findings of myocardial infarction. The culprit coronary arteries had severe lumen area stenosis greater than 90% at about 20 serial sections prepared at 500μm interval. These findings of MI-prone WHHL rabbits resembled those of human multivessel disease. Atheromatous plaques of the coronary arteries of WHHL rabbits were changed from fibromuscular type to macrophage/extracellular lipid-rich type by the selective breeding. Many coronary plaques showed occlusion by macrophage accumulation at the superficial area of the plaque. In this case, denudation of the endothelial cells was observed. Some others showed thin fibromuscular cap with large lipid core. In this case, macrophages were detected at the border between the attenuated fibromuscular cap and the lipid core. This finding was considered as vulnerable plaque, which probably causes plaque rupture and consequent occlusive thrombus formation. However, we did not detect any plaque rupture or luminal thrombus in the coronary arteries. This suggests that we can examine which factors are important as trigger of plaque rupture by using MI-prone WHHL rabbits. We consider that MI-prone WHHL rabbits will contribute to studies of myocardial infarction.
