Heterotopic hindlimb allotransplantation in rats: an alternative model for immunological research in composite-tissue allotransplantation.

A nonfunctional heterotopic hindlimb allotransplantation model is presented, and a study was performed between this model and standard orthotopic hindlimb transplantation to compare operation and ischemia time, overall morbidity, and mortality rates. In this model, the skin component of the hindlimb was stripped away to the ankle level, and the remaining part along with the vascularized epigastric skin was transplanted heterotopically to the inguinal space of the recipient. No osteotomy and intramedullary fixation were performed. Thirty heterotopic and orthotopic hindlimb transplantations were performed in two groups. Each group involved 15 transplantations from inbred, male Brown Norway (BN; RT1n) weighing 150-200 g to Lewis rats (LEW; RT1(1)) weighing 250-300 g. The animals were followed up for 2 weeks under immunosuppression with cyclosporine A (16 mg/kg/day). Mean operation times for heterotopic and orthotopic hindlimb transplantations were 60 and 105 min, with ischemia times of 35 and 85 min, respectively. No animal deaths or major complications were encountered in heterotopic hindlimb transplantation during the follow-up period. Seroma formation was observed in one animal as the only minor complication. The mortality rate for orthotopic hindlimb transplantation was 26.7%, and there were minor complications in 35%, including infection, ulceration, and loss of rigid fixation. This model circumvents the disadvantages of osteotomy and intramedullary fixation, which may increase the risk of blood loss, embolus, and infection in immunosuppressed animals. It also helps avoid tension or kinking on the anastomosis due to inadequate judgment of the osteotomy level, distortion associated with loss of rigid fixation, and weight mismatch between donor and recipient. From the immunological point of view, insult to bone marrow is avoided, and a relatively constant amount of bone marrow is introduced to be used in chimerism-based tolerance studies. We recommend this model for composite-tissue allotransplantation studies when functional recovery is not of primary importance. Copyright 2005 Wiley-Liss, Inc.