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 infants and children. Sources of possible concern with this procedure include the potential for autograft ischemia, patch dehiscence, and recurrent stenosis. Vascular endothelial growth factor is a potent angiogenic inducer (particularly in the setting of ischemia, hypoxia, or both) and is postulated to promote tissue healing. The purpose of this study was to test the hypothesis that pretreatment of tracheal autografts with topical vascular endothelial growth factor would enhance tracheal healing.


METHODS
In a rabbit model of tracheal reconstruction (n = 32), an elliptically 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 soaked in either vascular endothelial growth factor (5 microg/mL, n = 16) or normal saline solution (n = 16) for 15 minutes before being reimplanted in the resultant tracheal opening. Animals were killed and autografts were examined at 2 weeks, 1 month, and 2 months postoperatively for gross and microscopic characteristics.


RESULTS
By 2 weeks, and progressing through 1 and 2 months, autografts treated with vascular endothelial growth factor, as compared with control autografts, 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 treated 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 endothelial growth factor in a rabbit tracheal reconstruction model enhanced healing, as evidenced by accelerated autograft revascularization, reduced submucosal fibrosis and inflammation, and preservation of the normal tracheal architecture. Topical vascular endothelial growth factor may improve future results of tracheal reconstruction.
Dodge-Khatami
A
A
Northwestern University Medical School, Department of Surgery, Division of Cardiovascular-Thoracic Surgery, Children's Memorial Hospital, Chicago, Ill 60614-3394, USA.
Backer
C L
CL
Holinger
L D
LD
Mavroudis
C
C
Cook
K E
KE
Crawford
S E
SE
D000279:Administration, Cutaneous; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016228:Endothelial Growth Factors / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D005260:Female; D005355:Fibrosis; D007249:Inflammation; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011292:Premedication / Q000379:methods*; D011817:Rabbits; D011897:Random Allocation; D012008:Recurrence; D012720:Severity of Illness Index; D013529:Surgical Wound Dehiscence / Q000209:etiology / Q000523:psychology; D013997:Time Factors; D014132:Trachea / Q000637:transplantation*; D014135:Tracheal Stenosis / Q000145:classification / Q000151:congenital* / Q000473:pathology / Q000601:surgery*; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000187:drug effects*
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors