Background:

Functional outcomes following vascularized composite allotransplantation (VCA) have been promising, but there is still room for improvement. Studies to investigate strategies to overcome this obstacle are limited by the lack of a functional VCA animal model. To address this problem, we developed a novel forelimb transplant model in which functional recovery is tested by measuring progressive return of grip-strength within the transplanted forelimb.

Methods:

Orthotopic forelimb allotransplantation (Brown Norway to Lewis) is performed at mid-humerus level, with end-to-end suture anastomosis of brachial artery and vein. Median and radial nerves are approximated in the experimental group to innervate extrinsic flexor and extensor muscles, respectively, and left in discontinuity in the control group (N=8 per group). Weekly grip strength testing is performed with a force transducer device. At 12 weeks, all animals are sacrificed for median nerve histomorphometry and flexor digitorum neuromuscular junction analysis.

Results:

After an initial learning curve, forelimb transplantation can be performed with consistent success (operative time 180-220 minutes). Long-term graft survival (120 days) was achieved with immunosuppressive treatment. Allograft rejection without treatment occurred within 10 days. Animals reflexively use the transplanted forelimb to grasp a bar, with progressive improvement in grip strength observed beginning at 3 weeks. Statistical analysis of grip strength data, nerve histomorphometry and neuromuscular junction analysis are pending completion of study.

Conclusion:

Rat forelimb transplantation may represent the first VCA model that allows for reliable and reproducible measurement of functional recovery. Statistical analysis of grip strength data will elucidate the degree of variability at each time-point and the degree of improvement from week to week as compared to non-innervated controls.

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