Improving surgical wound healing with basic fibroblast growth factor after radiation.
OBJECTIVE
Delayed wound healing in surgical patients who have received previous irradiation continues to be a significant problem. We investigated whether radiation decreases basic fibroblast growth factor (bFGF) production in skin and whether supplemental bFGF can improve irradiated postsurgical soft tissue healing.


METHODS
Experimental study in the porcine skin flap model.


METHODS
Pigs were subjected to orthovoltage radiation (1,300 cGy). To test whether radiation alters bFGF production in skin, semiquantitation of bFGF message was compared in irradiated and nonirradiated skin by reverse transcription-polymerase chain reaction (RT-PCR). To determine whether supplemental bFGF can improve postsurgical soft tissue healing after radiation, bFGF was given intravenously or intracuticularly preoperatively. To investigate whether additional oxygen tissue levels would modify the effects of supplemental bFGF, one test group received hyperbaric oxygen. Six weeks later, 108 skin flaps (random and arterial) were created in 27 pigs and monitored over 2 weeks. Tissues were analyzed for flap viability, vascularity, endothelial cell apoptosis by caspase-3 activation, and histologic analysis.


RESULTS
Radiation statistically increased endothelial cell apoptosis in porcine skin by 650%. Radiation also significantly reduced bFGF message by 75% in porcine skin by RT-PCR analysis. Supplemental intravenous bFGF in irradiated tissue significantly increased skin flap viability by 25% compared with controls (P < .001). Intravenous bFGF also significantly reduced gastrointestinal side effects from irradiation by 50% compared with controls. BFGF treatment induced a trend to decrease endothelial cell apoptosis in irradiated skin, but this was not statistically significant. Histologically, the intravenous bFGF-treated flaps had similar cellularity, fibroblasts, and extracellular acid mucopolysaccharides as controls. When bFGF was administered by intracuticular injection with and without hyperbaric oxygen, skin flap survival and flap vascularity were similar to controls.


CONCLUSIONS
Decreased local levels of bFGF in skin may play an important role in the delayed healing of irradiated wounds. Radiation appears to decrease bFGF production by significantly reducing bFGF message in irradiated tissue. Supplemental intravenous bFGF reduced irradiated soft tissue injury and improved random skin flap viability in this porcine model. More studies are needed to investigate the effects of bFGF in the surgical healing of irradiated wounds.
Hom
David B
DB
Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Minnesota School of Medicine and, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
Unger
Gretchen M
GM
Pernell
Kerri J
KJ
Manivel
J Carlos
JC
D000818:Animals; D017209:Apoptosis; D004727:Endothelium / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000502:physiology*; D006931:Hyperbaric Oxygenation; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000628:therapy; D011835:Radiation Protection; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013524:Surgical Flaps; D013552:Swine; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology / Q000528:radiation effects*
D016222:Fibroblast Growth Factor 2