Enhancement of wound healing by hyperbaric oxygen and transforming growth factor beta3 in a new chronic wound model in aged rabbits.

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 beta(3) at 1 microg/cm(2); 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 beta(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 beta(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.

Transforming growth factor beta3 promotes fascial wound healing in a new animal model.

HYPOTHESIS: Transforming growth factor beta(3) (TGF-beta(3)) promotes fascial wound healing in a new animal model, as measured by wound breaking strength, collagen deposition, and cellular proliferation. DESIGN/INTERVENTION: Bilateral, longitudinal incisions were made in the anterior rectus sheaths of 24 male New Zealand white rabbits. One incision was treated with 1 microg of TGF-beta(3); the contralateral incision served as a control. The wounds were harvested at 1, 2, 3, 4, 6, and 8 weeks after creation ("wounding"). MAIN OUTCOME MEASURES: Wound tissue was tested for breaking strength using a tensiometer and processed for histological examination of collagen deposition and cellular proliferation at all time points after wounding. Collagen deposition and cellular proliferation were measured in histological cross sections of wounds with Masson trichrome staining and proliferating cell nuclear antigen immunohistochemistry, respectively. RESULTS: At all time points after wounding, treatment with TGF-beta(3) significantly increased the wound breaking strength (up to 138%) and collagen deposition (up to 150%) over the control group. Cellular proliferation was increased during the first 3 weeks after wounding (up to 147%), but returned to baseline levels by the fourth week. CONCLUSIONS: Transforming growth factor beta(3) promotes fascial wound healing. In this new animal model of fascial wound healing, TGF-beta(3) increased fascia breaking strength, collagen deposition, and cellular proliferation. These results are similar to findings in cutaneous wound models and demonstrate, for the first time, a pharmacologic agent to accelerate fascial healing.

Postlaparoscopic small bowel obstruction. Rethinking its management.

BACKGROUND: Patients with early postoperative small bowel obstruction (SBO) are usually managed nonoperatively with nasogastric suction, intravenous fluids, and observation. The majority of early postoperative SBO resolve without an operation. METHODS: We performed a retrospective review of patients who had been diagnosed with postlaparoscopic SBO at three Chicago area teaching hospitals. RESULTS: The patients were initially managed nonoperatively for up to 7 days. However, all of them subsequently required an operation. In every case, the postlaparoscopic SBO was caused by the small bowel being incarcerated in a peritoneal defect created either by trocar placement or peritoneal incision for herniorrhaphy. CONCLUSION: In contradistinction to the approach used for early SBO after laparotomy, prompt operative intervention for postlaparoscopic SBO is recommended.

Hyperbaric oxygen as a signal transducer: upregulation of platelet derived growth factor-beta receptor in the presence of HBO2 and PDGF.

The purpose of this study was to test the hypothesis that hyperbaric oxygen (HBO2) may function by modifying the signal transduction pathway of growth factors or their receptors, or both. Studies were conducted with platelet derived growth factor (PDGF) and HBO2 using an established rabbit ear wound model. PDGF, a dimeric compound composed of A chain and B chain components, is found as PDGF-A, AB, and BB. It exerts its effects on cells by binding to one of two membrane-bound receptors, the alpha receptor or the beta receptor. Acutely ischemic wounds in rabbit ears were treated with saline or PDGF-BB and then animals were treated with hyperbaric air or oxygen at 2 atm abs (202.6 kPa). Hyperbaric air was without significant effect compared with control rabbits who breathed air at ambient pressure. Combined treatment with HBO2 plus PDGF-BB was synergistic in upregulating mRNA for PDGF-beta receptor. No treatments, whether alone or in combination, altered mRNA levels for PDGF-alpha receptor or for PGDF-A.