Postoperative reduction of high serum cholesterol concentrations and experimental vein bypass grafts: Effect on the development of intimal hyperplasia and abnormal vasomotor function

Hypercholesterolemia is an important contributor to the development of intimal hyperplasia and superimposed accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary modification of serum cholesterol on the development of intimal hyperplasia and vasomotor function of vein grafts. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were put to death 28 days after the operation. Twenty animals received a 1% cholesterol diet for 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 procedure and continued until harvest (cholesterol reduction group). The last 10 animals were control subjects. Vein grafts were harvested either for histologic study or for in vitro isometric tension studies. Cumulative dose response curves to norepinephrine, serotonin, bradykinin, and endothelin-1 were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The change in diet produced a 74% reduction in serum cholesterol concentration within 28 days. There was a 26% reduction in the intimal thickness of vein graft intimal hyperplasia and the macroscopic disappearance of atheromatous lesions from the graft wall, which are always observed in vein grafts from the hypercholesterolemia group. Cholesterol reduction did not change hypercholesterolemia-induced agonist supersensitivity. Therefore, cholesterol reduction slows the formation of intimal hyperplasia in vein grafts but does not prevent the persistence of the hypercholesterolemia-associated smooth muscle phenotype.