title: Functional outcomes following multiple acute rejections in experimental vascularized composite allotransplantation.
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.
authors: 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.
authors: Jignesh V
authors: JV
authors: Unadkat
authors: Dennis
authors: D
authors: Bourbeau
authors: Paul N
authors: PN
authors: Afrooz
authors: Mario G
authors: MG
authors: Solari
authors: Kia M
authors: KM
authors: Washington
authors: Benson J
authors: BJ
authors: Pulikkottil
authors: Douglas J
authors: DJ
authors: Weber
authors: W P Andrew
authors: WPA
authors: Lee
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006084:Graft Rejection / Q000188:drug therapy / Q000503:physiopathology* / Q000517:prevention & control*; D006614:Hindlimb / Q000502:physiology* / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008124:Locomotion / Q000502:physiology; D008297:Male; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009416:Nerve Regeneration / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D011183:Postoperative Complications / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D020551:Pulse Therapy, Drug; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology / Q000601:surgery; D014184:Transplantation, Homologous
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016572:Cyclosporine
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