Topical vascular endothelial growth factor in rabbit tracheal surgery: comparative effect on healing using various reconstruction materials and intraluminal stents

OBJECTIVES: The effect of topical vascular endothelial growth factor (VEGF) on post-surgical tracheal healing using various reconstruction materials was studied, with particular regard to prevention of granulation tissue or fibrosis.

METHODS: Twenty-four New Zealand White rabbits underwent survival surgery using autograft patches (n=6), xenopericardium patches (n=6), intraluminal Palmaz wire stents (n=6), and controls (n=6). Autograft and pericardial half-patches were soaked in topical VEGF (5 microg/ml over 30 min) and saline before reimplantation. Stents and controls received circumferential injections of VEGF and saline in the tracheal wall. At 1-4 months postoperatively, specimens of sacrificed animals were stained with anti-VEGF antibody, followed by morphological and immunohistochemical examination.

RESULTS: Rabbits with autografts and controls fared well until planned sacrifice. After xenopericardium repair, obstructive intraluminal granulation tissue led to early sacrifice in three rabbits. Stent insertion led to earlier death from airway obstruction in all six rabbits. Topical VEGF reduced granulation tissue after pericardial repair and fibrosis in all repairs except in stents. Remarkably, VEGF-pretreated half-patches and saline half-patches stained similarly high for VEGF, suggesting also local production of VEGF, probably in plasmacells, and in submucosal glands.

CONCLUSIONS: Autograft repair induces the least granulation tissue and fibrosis, and the best healing pattern. Stents rapidly induced critical airway obstruction, unhindered by VEGF, leading to premature death. Tracheal pretreatment with topical VEGF reduces postoperative fibrosis after autograft and pericardial patch repairs, and reduces granulation tissue after xenopericardium repair. In time, VEGF is probably locally produced, although its potential role in tracheal healing remains to be established.