Document Detail

Prevention of allograft heart valve failure in a rat model.
MedLine Citation:
PMID:  11479504     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Allograft heart valves are commonly used in cardiac surgery. Despite mounting evidence that these valves are immunogenic, leading to premature failure, current clinical practice does not attempt to minimize or control such a response. The objective of this study was to evaluate immune modulatory approaches to ameliorate allograft valve failure in a rat model. METHOD: Aortic valve grafts were implanted infrarenally into Lewis rat recipients (n = 32). There were 4 transplant groups: syngeneic grafts (Lewis to Lewis), untreated allografts (Brown Norway to Lewis), allograft recipients treated with cyclosporine (INN: ciclosporin) (10 mg/kg per day for 7 or 28 days), and allograft recipients treated with anti-alpha4 integrin and anti-beta2 integrin monoclonal antibodies for 7 days. At 7 and 28 days the valves were examined for structural integrity and cellular infiltration. RESULTS: Both cyclosporine and anti-alpha4/beta2 integrin treatment resulted in significant reduction in leaflet infiltration by macrophages (ED1(+)), T cells (CD3(+)), and CD8(+) T cells at 7 days with preservation of structural integrity when compared with control allografts. Twenty-eight days after implantation, daily treatment with cyclosporine preserved leaflet structural integrity and inhibited cellular infiltration. However, a short course of cyclosporine (7 days) failed to prevent destruction of the valves at 28 days. CONCLUSIONS: Immune modulatory approaches aimed at T-cell activation or trafficking decrease leaflet cellular infiltration and prevent allograft valve structural failure. However, short-course therapy does not appear to be sufficient and must be maintained to allow long-term preservation of leaflet structural integrity (28 days).
J F Légaré; D B Ross; T B Issekutz; W Ruigrok; K Creaser; G M Hirsch; T D Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  122     ISSN:  0022-5223     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-07-31     Completed Date:  2001-09-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  310-7     Citation Subset:  AIM; IM    
Departments of Surgery, Pathology, and Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
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MeSH Terms
Analysis of Variance
Antibodies, Monoclonal / therapeutic use
Aortic Valve / immunology,  transplantation*
Cyclosporine / immunology,  therapeutic use
Flow Cytometry
Graft Rejection / immunology*,  prevention & control*
Heart Valve Prosthesis Implantation
Immunoenzyme Techniques
Immunosuppressive Agents / immunology,  therapeutic use*
Integrins / immunology,  therapeutic use
Rats, Inbred BN
Rats, Inbred Lew
Transplantation, Homologous
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Immunosuppressive Agents; 0/Integrins; 59865-13-3/Cyclosporine

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