Document Detail

Functional outcomes following multiple acute rejections in experimental vascularized composite allotransplantation.
MedLine Citation:
PMID:  23629111     Owner:  NLM     Status:  MEDLINE    
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.
Jignesh V Unadkat; Dennis Bourbeau; Paul N Afrooz; Mario G Solari; Kia M Washington; Benson J Pulikkottil; Douglas J Weber; W P Andrew Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Plastic and reconstructive surgery     Volume:  131     ISSN:  1529-4242     ISO Abbreviation:  Plast. Reconstr. Surg.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-30     Completed Date:  2013-07-16     Revised Date:  2014-10-13    
Medline Journal Info:
Nlm Unique ID:  1306050     Medline TA:  Plast Reconstr Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  720e-30e     Citation Subset:  AIM; IM    
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MeSH Terms
Acute Disease
Anti-Inflammatory Agents / pharmacology
Cyclosporine / pharmacology
Dexamethasone / pharmacology
Graft Rejection / drug therapy,  physiopathology*,  prevention & control*
Hindlimb / physiology*,  transplantation*
Immunosuppressive Agents / pharmacology
Locomotion / physiology
Muscular Atrophy / pathology,  physiopathology,  prevention & control
Nerve Regeneration / physiology
Neural Conduction / physiology
Postoperative Complications / pathology,  physiopathology,  prevention & control
Pulse Therapy, Drug
Rats, Inbred BN
Rats, Inbred Lew
Recovery of Function / physiology*
Sciatic Nerve / physiology,  surgery
Transplantation, Homologous
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Immunosuppressive Agents; 7S5I7G3JQL/Dexamethasone; 83HN0GTJ6D/Cyclosporine

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