Combination therapy of cholesterol reduction and L-arginine supplementation controls accelerated vein graft atheroma.
Hyperlipidemia contributes to the development of intimal hyperplasia and accelerated 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 observations by examining the effect of the combination therapy of cholesterol reduction and L-arginine supplementation on the development of intimal hyperplasia in vein grafts in hypercholesterolemic animals. Thirty New Zealand White rabbits 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 received a 1% cholesterol diet for 4 weeks prior to surgery. This diet was continued until harvest in ten animals. Ten cholesterol-fed animals received L-arginine supplementation (2 g/kg/day, p.o.) for 7 days preoperatively and thereafter until harvest and in addition were returned to a normal diet on the day of surgery. The last ten animals were controls (normal diet). Combined cholesterol reduction and L-arginine supplementation prevented accelerated atheroma in vein grafts, halted the change in enhanced smooth muscle cell contractility, and improved endothelial cell function. Early postoperative therapy targeting atheroma development in the high-risk patient could offer significant morphological and functional benefits.
Davies
M G
MG
Vascular Biology and Atherosclerosis Research Laboratory, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Fulton
G J
GJ
Huynh
T T
TT
Barber
L
L
Svendsen
E
E
Hagen
P O
PO
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002339:Carotid Arteries / Q000601:surgery; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D018752:Diet, Fat-Restricted; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000601:surgery; D006949:Hyperlipidemias / Q000517:prevention & control; D006965:Hyperplasia; D007601:Jugular Veins / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D008297:Male; D008854:Microscopy, Electron; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology; D014661:Vasoconstriction / Q000502:physiology
D002791:Cholesterol, Dietary; D001120:Arginine