POSTOPERATIVE REDUCTION OF HIGH SERUM-CHOLESTEROL CONCENTRATIONS AND EXPERIMENTAL VEIN BYPASS GRAFTS - EFFECT ON THE DEVELOPMENT OF INTERNAL HYPERPLASIA AND ABNORMAL VASOMOTOR FUNCTION

Hypercholesterolemia is an important contributor to the development of intimal hyperplasia and superimposed accelerated atherosclerosis in v ein bypass grafts. This study examines the effect of dietary modificat ion of serum cholesterol on the development of intimal hyperplasia and vasomotor function of vein grafts. Thirty male New Zealand White rabb its had a right carotid vein bypass graft and were put to death 28 day s after the operation. Twenty animals received a 1% cholesterol diet f or 4 weeks before the operation. In 10 animals this diet was continued until harvest (hypercholesterolemia group). In another 10 animals the diet was changed to standard rabbit chow on the day of the surgical p rocedure and continued until harvest (cholesterol reduction group). Th e last 10 animals were control subjects. Vein grafts were harvested ei ther for histologic study or for in vitro isometric tension studies. C umulative dose response curves to norepinephrine, serotonin, bradykini n, and endothelin-1 were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphomet ry. The change in diet produced a 74% reduction in serum cholesterol c oncentration within 28 days. There was a 26% reduction in the intimal thickness of vein graft intimal hyperplasia and the macroscopic disapp earance of atheromatous lesions from the graft wall, which are always observed in vein grafts from the hypercholesterolemia group. Cholester ol reduction did not change hypercholesterolemia-induced agonist super sensitivity. Therefore, cholesterol reduction slows the formation of i ntimal hyperplasia in vein grafts but does not prevent the persistence of the hypercholesterolemia-associated smooth muscle phenotype.