Circulation, Vol 87, 261-269, Copyright © 1993 by American Heart Association
DM Eich, JE Nestler, DE Johnson, GH Dworkin, D Ko, AS Wechsler and ML Hess
BACKGROUND. Accelerated coronary atherosclerosis has become a critical
problem in cardiac transplantation. Although the pathogenesis of this
disease is unknown, hypercholesterolemia has been shown to be a major risk
factor. METHODS AND RESULTS. To study this problem, a hypercholesterolemic
rabbit model of heterotopic cardiac transplantation was developed to study
accelerated graft atherosclerosis. Based on suggestions in the literature,
it was hypothesized that dehydroepiandrosterone (DHEA) may retard the
progression of the disease. Using semiquantitative light microscopy, a
predilection for the development of small vessel occlusive disease in the
transplanted hearts was found. Chronic DHEA administration produced a 45%
reduction in the number of significantly stenosed vessels in the
transplanted hearts (p < 0.05) compared with controls and a 62%
reduction in the nontransplanted hearts (p < 0.05), yielding an overall
50% reduction in the number of significantly stenosed vessels in both the
transplanted and nontransplanted hearts. This reduction in luminal stenosis
was observed in the absence of any significant alterations in lipid
profiles. CONCLUSIONS. It is concluded that chronic DHEA administration in
a hypercholesterolemic rabbit model of heterotopic cardiac transplantation
significantly retards the progression of accelerated atherosclerosis in
both the transplanted heart and in the native heart.
ARTICLES
Inhibition of accelerated coronary atherosclerosis with dehydroepiandrosterone in the heterotopic rabbit model of cardiac transplantation
Department of Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
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