HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Michael Weyand Frank Harig Teddy Fischlein Stephan M. Ensminger Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abele, S. Articles by Ensminger, S. M. Search for Related Content PubMed PubMed Citation Articles by Abele, S. Articles by Ensminger, S. M. Related Collections Cardiac - pharmacology Transplantation - heart

J Thorac Cardiovasc Surg 2006;131:1161-1166
© 2006 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Clopidogrel reduces the development of transplant arteriosclerosis

^a Department of Cardiac Surgery, Institute for Clinical Immunology, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, Germany
^b Department of Medicine III, Institute for Clinical Immunology, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, Germany
^c Department of Cardiothoracic Surgery, Deutsches Herzzentrum, Berlin, Germany

Received for publication September 20, 2005; revisions received December 6, 2005; accepted for publication January 13, 2006.

^_* Address for reprints: Stephan M. Ensminger, MD, DPhil, Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nuernberg, Krankenhausstrasse 12, 91054 Erlangen, Germany (Email: stephan.ensminger{at}herz.imed.uni-erlangen.de).

BACKGROUND: Transplant arteriosclerosis, the hallmark feature of chronic rejection, is still the major limiting factor for the long-term success of heart transplantation. Platelets have been implicated to play a role in the pathogenesis of this disease. Therefore the aim of this study was to investigate whether platelet inhibition alone has a positive effect on the development of transplant arteriosclerosis.

METHODS: Fully major histocompatibility complex–mismatched C57BL/6 (H2^b) donor aortas were transplanted into CBA (H2^k) recipients, and mice received different doses (1, 10, and 20 mg/kg) of clopidogrel or control saline as a daily intraperitoneal injection for 30 days. Blood was analyzed on days 2, 7, 14, and 30 by using a platelet aggregation test (adenosine diphosphate) for effectiveness of the treatment. Grafts were analyzed by means of histology and morphometry on day 30 after transplantation.

RESULTS: When mice were treated daily with 1 mg/kg clopidogrel in the absence of any other immunosuppression, transplant arteriosclerosis was significantly reduced compared with that seen in saline-treated control animals (intimal proliferation of 66% ± 9% [1 mg/kg clopidogrel] vs 77% ± 5% [control], n = 7, P .03). Daily application of 10 mg/kg and 20 mg/kg clopidogrel also significantly reduced the development of transplant arteriosclerosis compared with that seen in control animals (intimal proliferation of 61% ± 11% [10 mg/kg clopidogrel] vs 54% ± 10% [20 mg/kg clopidogrel] vs 77% ± 5% [control], n = 8, P .003). There was, however, no additional beneficial effect when compared with mice treated with 1 mg/kg clopidogrel (P = .06). Isografts did not show any signs of vascular lesions on day 30 after transplantation.

CONCLUSION: These results demonstrate that monotherapy with clopidogrel can effectively reduce the formation of transplant arteriosclerosis in a murine aortic allograft model.

This article has been cited by other articles:

				R. N. Mitchell and P. Libby Vascular Remodeling in Transplant Vasculopathy Circ. Res., April 13, 2007; 100(7): 967 - 978. [Abstract] [Full Text] [PDF]

				Chia Shu Hui, C. S. McLachlan, and M. Moursi Can Clopidogrel Monotherapy Influence Vascular Remodeling? Vascular and Endovascular Surgery, April 1, 2007; 41(2): 165 - 166. [PDF]