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Functional Outcomes following Multiple Acute Rejections in Experimental Vascularized Composite Allotransplantation

Unadkat, Jignesh V. M.D.; Bourbeau, Dennis Ph.D.; Afrooz, Paul N. M.D.; Solari, Mario G. M.D.; Washington, Kia M. M.D.; Pulikkottil, Benson J. M.D.; Weber, Douglas J. Ph.D.; Lee, W. P. Andrew M.D.

Plastic & Reconstructive Surgery:
doi: 10.1097/PRS.0b013e3182879e85
Experimental: Original Articles
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Author Information

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.

Received for publication April 6, 2012; accepted November 14, 2012.

Disclosure: None of the authors has a conflict of interest to declare.

This work was supported by THE PLASTIC SURGERY FOUNDATION.

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Presented, in part, at the 53rd Annual Meeting of the Plastic Surgery Research Council, in Springfield, Illinois, May 28 through 31, 2001; 63rd Annual Meeting of the American Society for Surgery of Hand, in Chicago, Illinois, September 18 through 20, 2008; 54th Annual Scientific Meeting of the Robert H. Ivy Society of Plastic Surgeons, in King of Prussia, Pennsylvania, April 12, 2008; 51st Annual Meeting of the Ohio Valley Society of Plastic Surgeons, in Cleveland, Ohio, May 16 through 18, 2008; the 94th Annual Clinical Congress of the American College of Surgeons, in San Francisco, California, October 12 though 16, 2008; and the First American Conference on Reconstructive Transplant Surgery, Philadelphia, Pennsylvania, July 18 through 19, 2008.

Department of Plastic and Reconstructive Surgery, University of Pittsburgh Medical Center, Suite 6b, Scaife Hall, 3550 Terrace Street, Pittsburgh, Pa. 15261, unadkatjv@upmc.edu

©2013American Society of Plastic Surgeons