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
Sheung-Fat Ko,
1
Hon-Kan Yip,
2
Steve Leu,
3
Chen-Chang Lee,
1
Jiunn-Jye Sheu,
4
Chia-Chang Lee,
3
Shu-Hang Ng,
1
Chung-Cheng Huang,
1
Min-Chi Chen,
5
and Cheuk-Kwan Sun
6
1
Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine,
123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
2
Department of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine,
123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
3
Center 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
4
Department of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine,
123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
5
Public 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
6
Department of Emergency Medicine, E-Da Hospital, I-Shou University, Number 1, Yi-Da Road, Kaohsiung 82445, Taiwan
Correspondence should be addressed to Sheung-Fat Ko; sfa.ko@msa.hinet.net
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. his 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.
his 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 let anterior descending artery ligation were randomized as tac-treated group (=6, with intracoronary tacrolimus
treatment) and controls ( = 6). CMR with cine and late gadolinium enhancement (LGE) studies were performed on postoperative
days 2, 5, and 21. here were no signiicant diferences in let ventricular function (LVF), contractility, and LGE between the two
groups on day 2. On day 5, the tac-treated group showed a signiicantly 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, signiicantly smaller infarct, and lower day-21/day-2 infarct
ratios compared with those on day 5 and controls. he in vivo CMR results were correlated with in vitro indings on histology,
immunostaining, and Western blotting which revealed signiicantly less ibrosis, higher vascularities, less CD68+ and CD40+
inlammatory cells, lower expressions of inlammatory (MMP-9, NF-B, and TNF-), and apoptotic (Bax, Caspase-3, c-PARP)
biomarkers, respectively, in tac-treated AMI minipigs than controls.
1. Introduction
Ischemic heart disease is one of the leading causes of
death worldwide [1]. Early reperfusion of the jeopardized
myocardium remains the most common approach to treating
acute myocardial infarction (AMI) [2]. However, reperfusion
harbors potential shortcomings, including myocardial stun-
ning, ventricular arrhythmia, and microvascular obstruc-
tion [3]. Recent studies have proposed that inlammatory
and immune reactions also play important roles in AMI
and that administrating immunosuppressive drugs to block
such reactions could potentially salvage the myocardium
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 524078, 13 pages
http://dx.doi.org/10.1155/2014/524078