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Enhancement of Wound Healing by Hyperbaric Oxygen and Transforming Growth Factor ₃ in a New Chronic Wound Model in Aged Rabbits

Steven R. Bonomo, MD; John D. Davidson, MD; John W. Tyrone, MD; Xuanhan Lin, DDS, MS; Thomas A. Mustoe, MD, FACS

Arch Surg. 2000;135:1148-1153.

Hypothesis  Although hyperbaric oxygen (HBO) has been used clinically for 3 decades, there have been few controlled clinical trials. Animal models have not been adequate to test the efficacy of HBO in the treatment of chronic wounds, either by itself or in combination with growth factors. We hypothesize that HBO is as efficacious as a prototype growth factor in improving wound healing in a new animal model of ischemic chronic wounds.

Design  Twenty-five aged rabbits and 3 young rabbits had their ears rendered chronically ischemic and ulcers were created down to the level of cartilage. These ulcers were treated in 1 of 3 ways: with HBO, 90 minutes per day, Monday through Friday, for 4 weeks; with transforming growth factor ₃ at 1 µg/cm²; or with both modalities combined. Controls were treated with vehicle or hyperbaric room air or both.

Results  This model created an aged/ischemic wound that failed to heal spontaneously up to 26 days after wounding (88% reduction compared with aged/nonischemic controls). Hyperbaric oxygen alone and transforming growth factor ₃ alone both improved healing rate (only 38% reduction in healing compared with aged/nonischemic controls). Combined therapy produced no additional improvement over either modality by itself.

Conclusions  In aged animals, HBO and transforming growth factor ₃ were equally effective in improving wound healing. Our data suggest that HBO alone may be more effective in the chronic wound than in the acute wound. There was no additive benefit to combining modalities as has been reported in the same wound model in young rabbits.

From the Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, Ill (Drs Lin and Mustoe); Department of General Surgery, Rush-Presbyterian-St Luke's Medical Center, Rush University, Chicago, Ill (Dr Bonomo); Division of Hyperbaric Medicine, St Luke's Hospital and Department of Medicine, Washington University School of Medicine, St Louis, Mo (Dr Davidson); and the Department of General Surgery, University of California-Davis–East Bay, Oakland (Dr Tyrone).

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