Hepatocyte growth factor prevents intimal hyperplasia in rabbit carotid expanded polytetrafluoroethylene grafting.
OBJECTIVE
The major cause of vascular prosthesis failure is anastomotic intimal hyperplasia caused by the proliferation and migration of smooth muscle cells. Hepatocyte growth factor (HGF) is an endothelium-specific growth factor that exerts a mitogenic action on endothelial cells. This study was designed to examine the effect of HGF on the suppression of intimal hyperplasia after small-caliber expanded polytetrafluoroethylene (ePTFE) grafting.


METHODS
An ePTFE graft, 2 mm in diameter and 30 mm in length, was implanted in the left common carotid arteries of Japanese white rabbits, after which the animals were fed with a 1.0% cholesterol diet. HGF was infused intravenously immediately and then every day for 7 days at doses of 0.3 mg/body (the 0.3-mg HGF group; n = 20) or 1.0 mg/body (the 1.0-mg HGF group; n = 17). A control group (n = 20) underwent infusion with saline solution. The rabbits were killed on postoperative days (PODs) 1, 2, 3, 5, 7, and 28.


RESULTS
The patency rates on POD 28 were 33%, 55%, and 100% in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and the 1.0-mg HGF group (P <.05). Endothelial-like cells were seen on the intraluminal surface of the graft only near the anastomotic site on POD 5 in the 1.0-mg HGF group. Intimal thickness at the distal anastomosis was 284 +/- 140 microm, 106 +/- 18 microm, and 67 +/- 10 microm in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.05). The number of anti-embryonic smooth muscle antibody positive cells at the distal anastomosis was 28.6 +/- 0.8, 3.8 +/- 2.8, and 3.9 +/- 0.9 in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.01).


CONCLUSIONS
HGF might suppress intimal thickness at the anastomotic site and improve the patency rate via rapid reendothelialization by POD 28 in a rabbit carotid ePTFE grafting model.
Harada
Masakazu
M
First Department of Surgery, Yamaguchi University School of Medicine, Ube, Japan.
Takenaka
Hiroaki
H
Ikenaga
Sigeru
S
Zhang
Hua
H
Zempo
Nobuya
N
Esato
Kensuke
K
Nagano
Tomokazu
T
Taiji
Mutsuo
M
Noguchi
Hiroshi
H
D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D017536:Carotid Artery, Common / Q000473:pathology* / Q000601:surgery; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011138:Polytetrafluoroethylene; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology*; D014654:Vascular Patency
D002791:Cholesterol, Dietary; D017228:Hepatocyte Growth Factor; D011138:Polytetrafluoroethylene