Pittsburgh, Pa.; Newark, N.J.; and Baltimore, Md. From the Department of Plastic and Reconstructive Surgery, University of Pittsburgh Medical Center, the Department of Physical Medicine and Rehabilitation, University of Pittsburgh, the Department of Surgery, University of Medicine and Dentistry of New Jersey, and the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University School of Medicine.
Plast Reconstr Surg. 2013 May;131(5):720e-730e. doi: 10.1097/PRS.0b013e3182879e85.
Vascularized composite allotransplantation has become a clinical reality. Patients undergoing vascularized composite allotransplantation have modest functional return. Most patients have had multiple acute rejections. The effect of multiple acute rejections influencing functional outcomes is unknown. This study systematically analyzes the effects of multiple acute rejections on functional outcome.
Rat functional orthotopic hind-limb transplants were performed from Brown-Norway to Lewis rats. Group 1 consisted of isografts. In group 2, daily cyclosporine was administered to prevent acute rejection. In group 3, recipients did not receive regular immunosuppression but received only pulsed cyclosporine and dexamethasone to rescue acute rejection. The study endpoint was 90 days. Muscle and sciatic nerve biopsy specimens were taken for histologic analyses. Hind-limb function was assessed using sciatic nerve axon density, nerve conduction velocity, and muscle force generated by the gastrocnemius muscle. Novel video kinematics was used to analyze gait.
By the endpoint, group 3 animals had 17 ± 5.1 acute rejections. Muscle biopsy showed significant atrophy and fibrosis in group 3 compared with groups 1 and 2. Withdrawal to pin prick was evident by days 31 ± 1.2, 30 ± 2.3, and 31 ± 3.7 in groups 1, 2, and 3, respectively. At the endpoint, there was no significant difference in the axon density or nerve conduction velocity among the three groups, but muscle force generated was significantly less in group 3. Gait was abnormal in group 3 animals compared with other groups.
In this study, multiple acute rejections induced muscle atrophy and fibrosis and consequent decreased function. This emphasizes the importance of preventing acute rejection to achieve optimum function following vascularized composite allotransplantation.
血管化复合组织移植已成为临床现实。接受血管化复合组织移植的患者仅有适度的功能恢复。大多数患者经历了多次急性排斥反应。多次急性排斥反应对功能结果的影响尚不清楚。本研究系统分析了多次急性排斥反应对功能结果的影响。
Brown-Norway 大鼠到 Lewis 大鼠的功能性原位后肢移植。第 1 组为同系移植物。第 2 组每天给予环孢素以预防急性排斥反应。第 3 组受者未接受常规免疫抑制，但仅接受脉冲环孢素和地塞米松抢救急性排斥反应。研究终点为 90 天。取肌肉和坐骨神经活检标本进行组织学分析。采用坐骨神经轴突密度、神经传导速度和腓肠肌产生的肌肉力量评估后肢功能。采用新型视频运动学分析步态。
在研究终点，第 3 组动物发生了 17±5.1 次急性排斥反应。肌肉活检显示，与第 1 组和第 2 组相比，第 3 组的肌肉明显萎缩和纤维化。第 1 组、第 2 组和第 3 组的触针退缩时间分别为第 31±1.2 天、第 30±2.3 天和第 31±3.7 天。在研究终点，三组之间的轴突密度或神经传导速度没有显著差异，但第 3 组的肌肉力量明显较小。与其他组相比，第 3 组动物的步态异常。
在这项研究中，多次急性排斥反应导致肌肉萎缩和纤维化，继而导致功能下降。这强调了预防急性排斥反应以实现血管化复合组织移植后最佳功能的重要性。
