When does atherosclerosis become irreversible? Chronological change from an early to an advanced atherosclerotic lesion observed by angioscopy.

Quite a large number of studies on atherosclerosis have been published to date. However, no report on the development and irreversibility of lesions has been published so far. The authors conducted the following experiments to examine in vivo lesions under direct vision. Atherosclerotic lesions were created in 11 Japanese macaques, and progress of the lesions was observed under changing feeding conditions. The efficacy of cholesterol-lowering therapy was also evaluated and the mechanism by which eicosapentaenoic acid (EPA) suppresses atherosclerosis was examined. The results of this long-term study were as follows: (1) Early lesions of atherosclerosis (fatty streaks) developed in the aortic wall owing to cholesterol loading disappeared when the serum concentration of total cholesterol was reduced. (2) Atheromas first developed at the orifices of major branches of the aorta. And even though serum cholesterol was reduced, the lesions gradually spread to nearby areas. (3) After atheromas developed, advancement of the lesions slowed, as assessed by angioscopy, when EPA was administered while cholesterol loading was continued. Thus, early lesions of atherosclerosis are reversible and cholesterol-lowering therapy is an effective treatment; however, since advanced lesions seem to be irreversible, cholesterol-lowering therapy may not be effective for such lesions. The results of angioscopic examination showed that EPA slowed the progression of atheromatous lesions, and probably suppression of the proliferation of smooth muscle cells is the mechanism of such effect.

Intraatrial rerouting by atrial flaps for partial anomalous pulmonary venous return.

We report a new surgical correction technique using an autologous atrial septal flap and anterolateral right atrial wall in a 3-year-old girl with partial anomalous pulmonary venous return and lower margin atrial septal defect. The patient recovered smoothly and is doing well 3 years after the operation.

Cholesterol-fed ovariectomized monkeys are good animal models for human atherosclerosis of postmenopausal women.

Although it is well known that the incidence of atherosclerosis is markedly increased in postmenopausal women, antiatherosclerotic effects of estrogen replacement therapies are not clear. One of the reasons for this is due to the lack of appropriate animal models for atherosclerosis of postmenopausal women. Therefore, we attempted to develop an animal model for atherosclerosis of postmenopausal women and examined the antiatherosclerotic effects of estrogen replacement therapy. Adult ovariectomized Japanese monkeys were fed 2% cholesterol diet alone (C-group) or in combination with conjugated estrogen (CE-group) for 30 months. The serum estradiol-17beta levels of the CE-group were varied between 10 and 204.5 ng/dl during treatment. In the C-group, the serum total cholesterol levels were increased from 110 to 270 mg/dl, and atheroma was first observed after 3-months treatment with angioscopy. In the CE-group, the levels of the serum total cholesterol during treatment were 30% lower than those of the C-group, and the aortic lesions were first observed after 12-months treatment with angioscopy. The aortic intimal thickness of the CE-group was 58% of the C-group. This finding showed good agreement with the angioscopic observation. The aortic lesions were of a fibromuscular type in both groups. In conclusion, a cholesterol-fed ovariectomized monkey is an appropriate animal model for atherosclerosis of postmenopausal women. Furthermore, angiofiberscopic and histopathological observations suggested that estrogen replacement therapy was valid for atherosclerosis of postmenopausal women.