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To develop a functional model for the study of whole limb transplantation, inbred Lewis rats were used as both donors and recipients. In this model, the recipient biceps femoris muscle was elevated from its distal attachment to preserve... more
To develop a functional model for the study of whole limb transplantation, inbred Lewis rats were used as both donors and recipients. In this model, the recipient biceps femoris muscle was elevated from its distal attachment to preserve part of the adductor function of the limb after surgery. The tibial, peroneal, and sural branches of the sciatic nerve were anastomosed separately to provide faster and more precise functional recovery. For control sensory evaluation, the saphenous branches of the femoral nerve were not reattached. A flat intramedullary pin stabilized with methyl methacrylate was used to rigidly immobilize the femur. The transplanted limbs started bearing weight at 17 to 22 days. Walking on the plantar surface of the hock and adduction of the toes gradually decreased, and the rats developed a normal walking pattern. Sciatic and tibial function indexes, based on walking track analysis, correlated well with clinical observations. In this study, a new model for limb transplantation was developed that provided good and reliable sensory and ambulatory recovery.
Experimental limb transplantation has been attempted since the turn of this century. The surgical procedures have involved a large variety of different tissues. Precise anatomic reconstruction is crucial for the return of optimal function. This makes limb transplantation very different from solid organ transplantation, as merely providing circulatory restoration does not guarantee an acceptable outcome. To better understand the control of allograft rejection and recovery after limb transplantation, a reliable, functional animal model is needed.
By the 1960s, most limb replantation/transplantation studies were performed using dogs because the anastomosis of blood vessels and nerves was much easier than in smaller animal models. Later, rat models became popular because of space, housing, and source considerations, as well as the need for inbred animals in transplantation studies. Since the first rat limb model was described in 1978, 1 satisfactory functional recovery (walking) has never been achieved. In most models, only muscle twitching, 2–4 tactile placing response, 5 or protective withdrawal movement 6,7 had been observed. Additionally, pain reaction could take 3 months or longer to recover. 8
Evaluation of limb function in experimental animals has been very difficult to interpret. Methods including histology, 8–10 immunochemistry, 11,12 neuromusculoelectrical activity, 8 muscle physiologic parameters (e.g., muscle shortening, contraction property, twitch tension, latency period, contraction time, half-relaxation time), 13 and axonal transport analysis were either too subjective or not quantifiable. Because only limited functional recovery was documented in earlier rat limb transplants, clinical assessment of function may have been adequate. However, in a model in which walking and sensory ability is regained in the transplanted limb, more objective and quantitative methods of evaluation are needed
Experimental limb transplantation has been attempted since the turn of this century. The surgical procedures have involved a large variety of different tissues. Precise anatomic reconstruction is crucial for the return of optimal function. This makes limb transplantation very different from solid organ transplantation, as merely providing circulatory restoration does not guarantee an acceptable outcome. To better understand the control of allograft rejection and recovery after limb transplantation, a reliable, functional animal model is needed.
By the 1960s, most limb replantation/transplantation studies were performed using dogs because the anastomosis of blood vessels and nerves was much easier than in smaller animal models. Later, rat models became popular because of space, housing, and source considerations, as well as the need for inbred animals in transplantation studies. Since the first rat limb model was described in 1978, 1 satisfactory functional recovery (walking) has never been achieved. In most models, only muscle twitching, 2–4 tactile placing response, 5 or protective withdrawal movement 6,7 had been observed. Additionally, pain reaction could take 3 months or longer to recover. 8
Evaluation of limb function in experimental animals has been very difficult to interpret. Methods including histology, 8–10 immunochemistry, 11,12 neuromusculoelectrical activity, 8 muscle physiologic parameters (e.g., muscle shortening, contraction property, twitch tension, latency period, contraction time, half-relaxation time), 13 and axonal transport analysis were either too subjective or not quantifiable. Because only limited functional recovery was documented in earlier rat limb transplants, clinical assessment of function may have been adequate. However, in a model in which walking and sensory ability is regained in the transplanted limb, more objective and quantitative methods of evaluation are needed