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BioMed Research International
Volume 2014, Article ID 524078, 13 pages
http://dx.doi.org/10.1155/2014/524078
Research Article

Therapeutic Potential of Tacrolimus on Acute Myocardial Infarction in Minipigs: Analysis with Serial Cardiac Magnetic Resonance and Changes at Histological and Protein Levels

1Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
2Department of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
3Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
4Department of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
5Public Health and Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
6Department of Emergency Medicine, E-Da Hospital, I-Shou University, Number 1, Yi-Da Road, Kaohsiung 82445, Taiwan

Received 20 March 2014; Revised 21 May 2014; Accepted 5 June 2014; Published 9 July 2014

Academic Editor: Giuseppe M. Sangiorgi

Copyright © 2014 Sheung-Fat Ko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study investigates the therapeutic potential of intracoronary tacrolimus against acute myocardial infarction (AMI) in minipigs with serial cardiac magnetic resonance (CMR) and changes at histological and protein levels. Twelve minipigs subjected to permanent left anterior descending artery ligation were randomized as tac-treated group (, with intracoronary tacrolimus treatment) and controls . CMR with cine and late gadolinium enhancement (LGE) studies were performed on postoperative days 2, 5, and 21. There were no significant differences in left ventricular function (LVF), contractility, and LGE between the two groups on day 2. On day 5, the tac-treated group showed a significantly higher ejection fraction, smaller infarct, and lower day-5/day-2 infarct ratio than controls. On day 21, the controls demonstrated further deterioration of LVF and infarct. Contrastingly, the tac-treated animals demonstrated preservation of LVF, contractility, significantly smaller infarct, and lower day-21/day-2 infarct ratios compared with those on day 5 and controls. The in vivo CMR results were correlated with in vitro findings on histology, immunostaining, and Western blotting which revealed significantly less fibrosis, higher vascularities, less CD68+ and CD40+ inflammatory cells, lower expressions of inflammatory (MMP-9, NF-B, and TNF-), and apoptotic (Bax, Caspase-3, c-PARP) biomarkers, respectively, in tac-treated AMI minipigs than controls.