Hyperbaric oxygen delays healing in an ischemic wound model

The true etiology of non-healing, chronic wounds remains elusive. One common denominator, whether the wounds are due to pressure, diabetes, or arterial insufficiency is localized tissue ischemia in the wound bed. Angiogenesis is an important process in tissue growth and development and therefore plays an integral role in wound healing. This study was designed to test the hypothesis that hyperbaric oxygen (HBO) will promote angiogenesis and therefore improve healing in a rat model of tissue ischemia. A rat model of tissue ischemia was used in which excisional wounds were centered on a 2.0 cm dorsal bipedicle skin flap with an intervening silicone sheet. In previous studies we have shown that the tissue remains ischemic up to 14 days, wound healing and tensile strength are impaired and lactate is elevated. After flap creation, 60 rats were divided into treatment and control groups, with the treatment group receiving daily HBO at 2.4 atm for 90 minutes. Wound surface area tracing and excision of the wound beds was performed on days 1, 3, 7, 10 and 14, with n = 6 per data point. The concentration of VEGF in wound extracts was quantified by ELISA and standardized for total protein. Data were expressed as mean ± SEM. The wound healing curves diverge at day 5, with HBO-treated wounds consistently larger and delayed in healing compared to control (day 7: HBO - 0.27 ± 0.02 cm² vs control - 0.17 ± 0.07 cm², day 14: HBO - 0.06 ± 0.04 vs cm² vs control - 0.03 ± 0.02 cm²). VEGF is greater at all time points in the control wounds with a peak at day 10 (HBO: 159 ± 55 pg/mg protein vs control: 244 ± 61 pg/mg protein). Non-ischemic wounds expressed low levels of VEGF, which was unchanged by hyperbaric treatment throughout the course of healing. HBO suppresses the expression of VEGF and delays healing in a model of tissue ischemia. Ongoing studies will analyze the effect of HBO on matrix metalloproteinase expression and the relationship between the angiogenic factors, oxidative stress and neovascularization.