Healing of a free tracheal autograft is enhanced by topical vascular endothelial growth factor in an experimental rabbit model

Objective: In 1996, we introduced the free tracheal autograft technique for repair of congenital tracheal stenosis from complete tracheal rings in inf ants and children. Sources of possible concern with this procedure include the potential for autograft ischemia, patch dehiscence, and recurrent steno sis. Vascular endothelial growth factor is a potent angiogenic inducer (par ticularly in the setting of ischemia, hypoxia, or both) and is postulated t o promote tissue healing. The purpose of this study was to test the hypothe sis that pretreatment of tracheal autografts with topical vascular endothel ial growth factor would enhance tracheal healing. Methods: In a rabbit model of tracheal reconstruction (n = 32), an elliptic ally shaped portion of the anterior tracheal wall was excised. The excised portion of trachea was one third of the tracheal circumference and 2 cm in length (6 tracheal rings). This portion of trachea (the autograft) was soak ed in either vascular endothelial growth factor (5 mug/mL, n = 16) or norma l saline solution (n = 16) for 15 minutes before being reimplanted in the r esultant tracheal opening. Animals were killed and autografts were examined at 2 weeks, 1 month, and 2 months postoperatively for gross and microscopi c characteristics. Results: By 2 weeks, and progressing through 1 and 2 months, autografts tre ated with vascular endothelial growth factor, as compared with control auto grafts, had reduced luminal stenosis, submucosal fibrosis, and inflammatory infiltrate (P <.05). The autografts tended to become malaligned in control animals, whereas the tracheal architecture was preserved in rabbits treate d with vascular endothelial growth factor. Microvascular vessel density was significantly greater in all vascular endothelial growth factor groups (P <.05) at all time intervals. Conclusions: Topical treatment of free tracheal autografts with vascular en dothelial growth factor in a rabbit tracheal reconstruction model enhanced healing, as evidenced by accelerated autograft revascularization, reduced s ubmucosal fibrosis and inflammation, and preservation of the normal trachea l architecture. Topical vascular endothelial growth factor may improve futu re results of tracheal reconstruction.