Hyperbaric oxygen and cyclosporine as a combined treatment regimen to prevent skin allograft rejection in immunohistoincompatible mice

Several previous studies reported various immunosuppressive effects of hyperbaric oxygen on nonspecific and specific cell-mediated reactions. A highly immunogenic skin allograft mouse model was used to evaluate the clinical relevance of the previously described immunosuppressive effects of hyperbaric oxygen. A 1.5 x 2.0-cm full-thickness skin allograft was cross-grafted between paired immunohistoincompatible mouse strains (N = 40, C57BL/6 and BALB/c female mice) that were randomly assigned to four groups receiving (1) no treatment (controls), (2) cyclosporine 1 mg per kilogram intraperitoneally daily, (3) cyclosporine plus a low-dose hyperbaric oxygen treatment (two treatments per day, once a week), and (4) cyclosporine plus a high-dose hyperbaric oxygen treatment (two treatments per day, three times a week) following surgery (N = 32). Allograft samples were taken from each group at day 9 after cross-grafting (N = 8). Skin allograft rejection was significantly delayed in all treatment groups compared to controls. No difference was found between animals who received cyclosporine only and the combined treatment regimen including low-dose hyperbaric oxygen. High-dose hyperbaric oxygen treatment in combination with cyclosporine substantially prolonged skin allograft survival compared to other treatments. These findings were histologically confirmed. We conclude that hyperbaric oxygen treatment as an adjunct to standard immunosuppressive therapy may only be advantageous if frequently applied.