Effect of ischemia on growth factor enhancement of incisional wound healing

Abstract

Several growth factors have been shown to enhance incisional wound healing in different models, but the models have been difficult to compare, and the effects under ischemic conditions are unknown. An ischemic model was developed by selective interruption of the rabbit ear circulation and placement of dorsal incisions. The model was defined during a 28-day period by use of serial blood gas analysis, breaking strength measurement, and histologic analysis. In a separate experiment, incisions were treated with topical growth factors with the contralateral ear serving as paired controls, and the wounds were evaluated similarly. The ischemic ears were more hypoxic than controls through day 14 after wounding (48.5 versus 41 mm Hg, p < 0.03), and healing was impaired through day 28 (3.21 versus 1.90 newtons, p < or = 0.001). Transforming growth factor-beta (1 microgram) and Kaposi's fibroblast growth factor (20 micrograms) increased breaking strengths under both normal (3.03 versus 2.41 and 2.83 versus 2.47 newtons, respectively; p < 0.05) and ischemic conditions (1.40 versus 1.11 and 1.56 versus 1.23 newtons, respectively; p < 0.05). Platelet-derived growth factor-BB (10 micrograms) was effective only under normal conditions (2.67 versus 2.15 newtons, p < 0.02), whereas basic fibroblast growth factor (20 micrograms) was ineffective under both conditions. The rabbit ear incisional model is a reproducible ischemic incisional model allowing comparison of growth factor effects under ischemic and nonischemic conditions. Transforming growth factor-beta and Kaposi's fibroblast growth factor are both effective under ischemic conditions, whereas basic fibroblast growth factor and platelet-derived growth factor-BB are not, suggesting that ischemia is an important parameter affecting growth factor actions.