Combination therapy of cholesterol reduction and L-arginine supplementation controls accelerated vein graft atheroma

Hyperlipidemia contributes to the development of intimal hyperplasia and ac celerated atheroma in vein bypass grafts. Dietary cholesterol reduction and oral supplementation with L-arginine have been shown to reduce accelerated atheroma in experimental vein grafts. This study extends these observation s by examining the effect of the combination therapy of cholesterol reducti on and L-arginine supplementation on the development of intimal hyperplasia in vein grafts in hypercholesterolemic animals. Thirty New Zealand White r abbits had a carotid vein bypass graft performed and were sacrificed at 28 days postoperatively either for morphology (light and electron microscopy) and videomorphometry, or for in vitro contractile studies. Twenty animals r eceived a 1% cholesterol diet for 4 weeks prior to surgery. This diet was c ontinued until harvest in ten animals. Ten cholesterol-fed animals received L-arginine supplementation (2 g/kg/day, p.o.) for 7 days preoperatively an d thereafter until harvest and in addition were returned to a normal diet o n the day of surgery. The last ten animals were controls (normal diet). Com bined cholesterol reduction and L-arginine supplementation prevented accele rated atheroma in vein grafts, halted the change in enhanced smooth muscle cell contractility, and improved endothelial cell function. Early postopera tive therapy targeting atheroma development in the high-risk patient could offer significant morphological and functional benefits.