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Biomed Res Int. 2014;2014:524078. doi: 10.1155/2014/524078. Epub 2014 Jul 9.

Therapeutic potential of tacrolimus on acute myocardial infarction in minipigs: analysis with serial cardiac magnetic resonance and changes at histological and protein levels.

Author information

  • 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.

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 (n=6, with intracoronary tacrolimus treatment) and controls (n=6). 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-κB, and TNF-α), and apoptotic (Bax, Caspase-3, c-PARP) biomarkers, respectively, in tac-treated AMI minipigs than controls.

PMID:
25114905
PMCID:
PMC4119637
DOI:
10.1155/2014/524078
[PubMed - indexed for MEDLINE]
Free PMC Article
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