TRANSFORMING GROWTH-FACTOR BETA(1) IMPROVES WOUND-HEALING AND RANDOM FLAP SURVIVAL IN NORMAL AND IRRADIATED RATS

Objectives: To evaluate the effect of chronic irradiation on wound hea ling and random flap survival (FV), and the effect of transforming gro wth factor beta(1) (TGF beta(1)) in this setting using an animal model . Design: A randomized, controlled study with four groups of rats to s tudy the effect of irradiation 4 months before surgical intervention. The effect of TGF-beta(1) on FV and wound healing also was evaluated i n the irradiated and nonirradiated groups. Subjects: Ninety-five rats were available for evaluation. Group 1 (n=10) was the control; group 2 (n=28) received TGF-beta(1); group 3 (n=28) received radiation therap y; and group 4 (n=29) received radiation therapy and TGF-beta(1). Inte rvention: The irradiated groups received 15 Gy to their dorsal skin. F our months later all received McFarlane skin flaps. Groups 2 and 4 rec eived topical TGF-beta(1), 4 mu g, to the bed of the flap; groups 1 an d 3 received saline. On postoperative day 7 all rats were evaluated fo r tensile strength and FV, and histologic staining with hematoxylin-eo sin for collagen and TGF-beta(1) was done. The slides were evaluated i n a ''blinded'' fashion. Results: Irradiation decreased tensile streng th and FV, but not to a notable degree. Transforming growth factor bet a(1) improved tensile strength in the irradiated (P=.04, Student's t t est) and nonirradiated groups (P=.05, Student's t test). Transforming growth factor beta(1) also improved FV in all groups, but significantl y in the irradiation plus TGF-beta(1) group (P=.001, Student's t test) . The TGF-beta(1) group had the most mature collagen present at the wo und edge. No qualitative difference was seen in the immunohistochemica l staining for the four groups. Conclusions: Transforming growth facto r beta(1) improves wound healing and random FV in radiated and nonirra diated rat skin. Further study is needed to determine the radiation do se necessary to create an ''impaired woundhealing model'' in rats, and the optimum dose of TGF-beta(1) in this setting.