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The effects of AEB071 (sotrastaurin) with tacrolimus on rat heterotopic cardiac allograft rejection and survival

Authors
 Yu Hui Fang ; Dong Jin Joo ; Yu Seun Kim ; Hwal Suh ; Myoung Soo Kim ; Kyu Ha Huh ; Beom Jin Lim 
Citation
 Journal of Surgical Research, Vol.171(1) : e131~e137, 2011 
Journal Title
 Journal of Surgical Research 
ISSN
 0022-4804 
Issue Date
2011
Abstract
BACKGROUND: AEB071 (sotrastaurin) is a specific inhibitor of protein kinase C that prevents T-cell activation. Our previous study demonstrated that AEB071 monotherapy could prevent acute cardiac allograft rejection in rats. Herein, we investigated the effects of AEB071 combined with various doses of tacrolimus (Tac) on the allograft rejection and survival in a rat heart transplantation model. MATERIALS AND METHODS: Heterotopic cardiac transplantation from Brown-Norway to Lewis rats was performed. Cardiac allograft survival was assessed by monitoring heartbeats in six recipients of each experimental group. Another four recipient rats were selectively sacrificed in each group at d 7 post-transplantation for histologic examination. Serum transaminases, blood urea nitrogen, and creatinine concentrations were measured. RESULTS: AEB071 monotherapy prolonged allograft mean survival time (MST) compared with the untreated control group. Also a combination of AEB071 and Tac prolonged MST compared with monotherapy groups with higher dose of Tac. In the cardiac graft histology, AEB071 combined with Tac 0.6 mg/kg/d significantly decreased the rejection grade as indicative of decreased inflammatory cell infiltration into the graft. No experimental group was found with any abnormal histologic or serologic evidence of liver and kidney toxicity. CONCLUSION: AEB071 combined with a smaller dosage of Tac may be clinically possible to establish calcineurin inhibitor (CNI) minimization protocol in solid organ transplantation.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/93825
DOI
10.1016/j.jss.2011.06.039
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Surgery
1. 연구논문 > 1. College of Medicine > Dept. of Medical Engineering
1. 연구논문 > 1. College of Medicine > Dept. of Pathology
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0022480411005890
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