Administration of granulocyte colony-stimulating factor enhances endothelialization and microvessel formation in small-caliber synthetic vascular grafts

Abstract

Objective: The purpose of this study was to determine whether systemic administration of granulocyte colony-stimulating factor (G-CSF) would promote endothelialization for small-caliber Dacron vascular grafts. Methods: We implanted 4-mm preclotted Dacron grafts in both carotids of 12 dogs. For a fair comparison, all dogs had a comparable platelet aggregation profile with platelet aggregation scores less than 30. Five dogs served as controls, and the others were given 7-day subcutaneous injections of G-CSF (10 μg/kg per day), starting on the seventh postoperative day. The effect of G-CSF was evaluated by white blood cell count, which showed a 3.7-fold (± 2.7-fold) increase at the end of treatment. Grafts were harvested at 4 weeks. All G-CSF grafts were patent, and one control occluded. Endothelial-like cell coverage averaged 80.8% on G-CSF grafts, but only 35.6% for control grafts (P < .0004). With the exclusion of the anastomotic pannus healing factor, the difference in endothelial-like cell coverage was even greater (68.5% vs 9.8%; P < .0001). Immunocytochemical staining and electron microscopy studies demonstrated endothelial cells. Light microscopy also showed that there were more microvessels on and in the G-CSF grafts than in the control grafts. This study suggests that G-CSF can enhance early endothelialization of small- caliber vascular grafts. Further studies to determine the proper dosage and timing are needed before clinical application can be recommended.