Distribution and progression of coronary arterial and aortic lesions in the conventional Watanabe heritable hyperlipidemic rabbit--quantitative analysis.

The distribution and progression of coronary arterial and aortic lesions were examined in 40 conventional Watanabe heritable hyperlipidemic (WHHL) rabbits. They were classified according to age into stage I (3-5 months old, 14 rabbits), stage II (6-12 months old; 12 rabbits) and stage III (14-28 months old; 14 rabbits). Fifteen normal Japanese rabbits served as controls. The findings obtained from serial and transverse sections of each of the extramural coronary arteries (ECA) and transverse sections of 4 to 5 equal pieces of whole ventricle for intramural coronary arteries (ICA) were quantified by an image analyzer. Atherosclerosis with positive Sudan III stain was seen in aorta, ECA and ICA over 200 mu in diameter. Atherosclerotic lesions were noted in the aortic arch in stage I rabbits and in the whole aorta in stages II and III rabbits. In ECA, stenosis due to atherosclerosis was noted in 14, 33 and 93% of stages I, II and III rabbits, respectively. Stenosis of over 75% in the orifices of the left and right coronary arteries was noted frequently (71%), while mural thrombi, hemorrhage, intimal rupture and recanalization were seen rarely. Striking features were non-atherosclerotic stenosis with negative Sudan III, seen in the ICA less than 200 mu in diameter of almost all the hearts of stages II and III rabbits. Acute and old myocardial infarction appeared in 5 of the 14 hearts of the stage III rabbits and the infarct-related ECA showed severe stenosis of over 90%. In conclusion, to detect coronary atherosclerosis, serial and transverse sections of ECA are needed. In conventional WHHL rabbits, the incidence of stenosis in ECA is very high, compared with that of the previous reports, and myocardial infarction is due to severe stenosis in ECA. Non-atherosclerotic lesions in ICA occur before the appearance of the atherosclerotic lesions in ECA.