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Hepatocyte growth factor prevents intimal hyperplasia in rabbit carotid expanded polytetrafluoroethylene grafting
Masakazu Harada1, Hiroaki Takenaka, Sigeru Ikenaga
1First Department of Surgery, Yamaguchi University School of Medicine, Ube, Japan.
Purpose:
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).
Conclusion:
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.