Effects of Mycophenolate Mofetil on Cardiac Allograft Survival and Cardiac Allograft Vasculopathy in Miniature Swine
| Autor: | Stuart L. Houser, James S. Allan, Ashok Muniappan, Margaret L. Schwarze, Isabel M. McMorrow, M.E. Maloney, Matthew T. Menard, Joren C. Madsen |
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| Rok vydání: | 2005 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Swine medicine.medical_treatment Miniature swine Mycophenolate Gastroenterology Mycophenolic acid Interferon Internal medicine medicine Animals Heart transplantation Cardiac allograft business.industry Graft Survival Respiratory disease Mycophenolic Acid medicine.disease Surgery Transplantation surgical procedures operative Heart Transplantation Swine Miniature Cardiology and Cardiovascular Medicine business Immunosuppressive Agents medicine.drug |
| Zdroj: | The Annals of Thoracic Surgery. 80:1787-1793 |
| ISSN: | 0003-4975 |
| DOI: | 10.1016/j.athoracsur.2005.04.054 |
| Popis: | Background Chronic rejection, as manifested by cardiac allograft vasculopathy, remains the leading cause of late graft failure in heart transplant recipients. Despite recent clinical trials, the efficacy of mycophenolate mofetil in preventing human cardiac allograft vasculopathy remains controversial. We investigated whether mycophenolate mofetil would prevent cardiac allograft vasculopathy and prolong cardiac allograft survival in our well-established miniature swine model of heart transplantation. Methods Hearts disparate at the major histocompatibility complex class I locus were heterotopically transplanted into miniature swine recipients treated with a 12-day course of mycophenolate mofetil (n = 3) or cyclosporine A (n = 3). Allograft survival, acute rejection, and chronic rejection were monitored in the two groups. Results Hearts transplanted with 12 days of cyclosporine were rejected between 46 and 61 days, whereas two of the three hearts transplanted with mycophenolate mofetil remained beating beyond 120 days ( p = 0.02). At necropsy, there was a 4.9% mean prevalence of cardiac allograft vasculopathy in the mycophenolate mofetil group as compared with 16.6% in the cyclosporine group ( p = 0.03). Cardiac allograft rejection and vasculopathy in the cyclosporine-treated group was associated with prominent myocardial interferon-γ gene expression, a finding absent in two thirds of the mycophenolate mofetil-treated swine. Moreover, the mycophenolate mofetil-treated swine failed to develop IgM or IgG alloantibodies. Conclusions A short course of mycophenolate mofetil resulted in a longer allograft survival than a similar course of cyclosporine. Moreover, mycophenolate mofetil reduced the prevalence of cardiac allograft vasculopathy as compared with cyclosporine-treated controls. The salutary effect of mycophenolate mofetil may be related to its ability to decrease interferon-γ expression in the myocardium and prevent the generation of alloantibodies. |
| Databáze: | OpenAIRE |
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