ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Stuart L. Houser
James S. Allan
Joren C. Madsen
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schwarze, M. L.
Right arrow Articles by Madsen, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwarze, M. L.
Right arrow Articles by Madsen, J. C.
Related Collections
Right arrow Transplantation - heart

Ann Thorac Surg 2005;80:1787-1793
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Effects of Mycophenolate Mofetil on Cardiac Allograft Survival and Cardiac Allograft Vasculopathy in Miniature Swine

Margaret L. Schwarze, MD a , Stuart L. Houser, MD b , Ashok Muniappan, MD a , James S. Allan, MD a , c , Matthew T. Menard, MD a , Isabel McMorrow, PhD a , Michaella E. Maloney, BA a , Joren C. Madsen, MD, DPhil a , d , *

a Transplantation Biology Research Center, Department of Surgery, Boston, Massachusetts, USA
b Department of Pathology, Boston, Massachusetts, USA
c Division of Thoracic Surgery, Department of Surgery, Boston, Massachusetts, USA
d Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Accepted for publication April 26, 2005.

* Address correspondence to Dr Madsen, Massachusetts General Hospital, 55 Fruit Street, BUL-01-119, Boston, MA 02114 (Email: madsen{at}helix.mgh.harvard.edu).

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-{gamma} 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-{gamma} expression in the myocardium and prevent the generation of alloantibodies.




This article has been cited by other articles:


Home page
 CirculationHome page
E. Raichlin, J.-H. Bae, Z. Khalpey, B. S. Edwards, W. K. Kremers, A. L. Clavell, R. J. Rodeheffer, R. P. Frantz, C. Rihal, A. Lerman, et al.
Conversion to Sirolimus as Primary Immunosuppression Attenuates the Progression of Allograft Vasculopathy After Cardiac Transplantation
Circulation, December 4, 2007; 116(23): 2726 - 2733.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2005 by The Society of Thoracic Surgeons.