title: Therapeutic potential of tacrolimus on acute myocardial infarction in minipigs: analysis with serial cardiac magnetic resonance and changes at histological and protein levels.
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.
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan.
authors.forename: Sheung-Fat
authors.identifier: 0000-0002-9524-6999
authors.initials: SF
authors.lastname: Ko
authors.affiliation: Department of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
authors.affiliation: 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.
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan.
authors.forename: Chen-Chang
authors.initials: CC
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.affiliation: 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.
authors.forename: Chia-Chang
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan.
authors.forename: Shu-Hang
authors.initials: SH
authors.lastname: Ng
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan.
authors.forename: Chung-Cheng
authors.identifier: 0000-0002-3622-1222
authors.initials: CC
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Min-Chi
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, E-Da Hospital, I-Shou University, Number 1, Yi-Da Road, Kaohsiung 82445, Taiwan.
authors.forename: Cheuk-Kwan
authors.identifier: 0000-0002-2524-9684
authors.initials: CK
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis*; D057791:Cardiac Imaging Techniques; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology*; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; D016559:Tacrolimus