Key result
Selective breeding of WHHL rabbits into the WHHLMI strain increased the cumulative incidence of fatal myocardial infarction between 11 and 35 months of age from 21% to 90%, associated with marked progression of coronary atherosclerosis.
Absolute Event Rate: 90% vs 21%
Selective breeding of WHHL rabbits produced a strain (WHHLMI) with markedly progressive coronary atherosclerosis that spontaneously develops fatal myocardial infarction, providing a useful animal model for ischemic heart disease.
No immediate clinical implications; extends preclinical tools for spontaneous fatal MI research.
Recently, we developed myocardial infarction-prone WHHLMI rabbits from coronary atherosclerosis-prone WHHL rabbits (WHHLCA rabbits) by selective breeding. In this study, we examined the relation of atherosclerotic plaques to the onset of myocardial infarction. We examined myocardial lesions of 378 WHHL rabbits born between 1992 and 2000, and atherosclerosis lesions of 93 WHHLCA and 82 WHHLMI rabbits. The aortic lesions were evaluated as percent surface lesion area. The coronary lesions were evaluated as cross sectional narrowing using sections prepared at 500 or 1,000 microm intervals. Serum lipid levels were assayed with enzymatic methods. The cumulative incidence of fatal myocardial infarction between 11 and 35 months old was 90% in WHHLMI rabbits and 21% in WHHLCA rabbits, respectively. Selective breeding increased the serum cholesterol levels by about 200 mg/dl despite there being no changes in triglyceride levels. Aortic and coronary atherosclerosis progressed markedly in WHHLMI rabbits compared to WHHLCA rabbits. Especially, WHHLMI rabbits over 15 months old showed more than 90% cross sectional narrowing of the left circumflex arteries, main stem of the left coronary artery, and the origin portion of the right coronary artery. In addition, there were no gender differences in atherosclerotic lesions of both aortas and coronary arteries. In conclusion, the present study showed that marked progression of coronary atherosclerosis was probably associated with spontaneous development of myocardial infarction in WHHLMI rabbits.
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Ito et al. (2004) studied Coronary atherosclerosis and spontaneous myocardial infarction (n=931). WHHLMI strain (selective breeding) vs. WHHLCA strain was evaluated on Cumulative incidence of fatal myocardial infarction between 11 and 35 months old. Selective breeding of WHHL rabbits into the WHHLMI strain increased the cumulative incidence of fatal myocardial infarction between 11 and 35 months of age from 21% to 90%, associated with marked progression of coronary atherosclerosis.
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