Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous Wound Repair
OBJECTIVE To test the influence of hyperbaric oxygen (HBO), platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-beta 1 (TGF-beta 1) on the deficit in wound healing produced by ischemia in a noncontractive dermal ulcer standardized model in the rabbit ear. DESIGN AND INTERVENTIONS Dermal ulcers were created in the ischemic ears of 42 anesthetized young female New Zealand white rabbits. The controls were ulcers created in nonischemic ears of eight anesthetized young female New Zealand white rabbits. Either PDGF-BB (5 micrograms), TGF-beta 1 (1 microgram), or buffer alone was applied to each wound, which was then covered. Some groups were treated with HBO on days 0 through 4. Wounds were harvested on day 7 and were evaluated histologically. MAIN OUTCOME MEASURES The amount of epithelial regrowth and granulation tissue production were measured. The wounds were evaluated for glycosaminoglycan and collagen content. Angiogenesis was measured. RESULTS Hyperbaric oxygen alone, in the ischemic model, increased the production of new granulation tissue by approximately 100% at 7 days without significantly affecting new epithelial growth (P = .03). In contrast, PDGF-BB and TGF-beta 1 each increased the new granulation tissue volume by greater than 200% in 7 days (P = .0001) and also had a statistically significant effect on new epithelial growth. However, the addition of growth factors to HBO treatment produced a synergistic total reversal of the wound-healing deficit produced by ischemia (P = .0001). CONCLUSIONS Both PDGF-BB and TGF-beta 1 alone are more effective than HBO treatment by itself in accelerating the impaired wound healing produced by ischemia. However, the combination of HBO with either of the growth factors has a synergistic effect that totally reverses the deficit produced by ischemia.