Intra-coronary administration of tacrolimus markedly attenuates infarct size and preserves heart function in porcine myocardial infarction.
BACKGROUND
We test the hypothesis that intra-coronary tacrolimus administration can limit infarct size and preserve left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) through ligating left anterior descending coronary artery (LAD) in mini-pigs.


METHODS
Twelve male mini-pigs were randomized into AMI-saline (MI-only) group and AMI-tacrolimus (MI-Tac) group that received intra-coronary saline (3.0 mL) and tacrolimus (0.5 mg in 2.5 mL saline) injection, respectively, beyond site of ligation 30 minutes after LAD occlusion.


RESULTS
Larger infarct area was noted in MI-only group (p < 0.001). Inflammatory biomarkers at protein [oxidative stress, tumor necrotic factor-α, nuclear factor-κB], gene (matrix metalloproteinase-9, plasminogen activator inhibitor-1), and cellular (CD40+, CD68+ inflammatory cells) levels were remarkably higher in MI-only animals (p < 0.01). Conversely, anti-inflammatory biomarkers at gene level (Interleukin-10), gene and protein level (endothelial nitric oxide synthase), and anti-oxidant biomarkers at both gene and protein levels [heme oxygenase 1, NAD(P)H:quinone oxidoreductase] were lower in MI-only group (p < 0.01). Number of apoptotic nuclei and apoptotic biomarkers expressions at gene and protein levels (Bax, caspase 3) were notably higher, whereas anti-apoptotic biomarkers at gene and protein levels (Bcl-2), LVEF, and fractional shortening were markedly lower in MI-only group (p < 0.001).


CONCLUSIONS
Intra-coronary administration of tacrolimus significantly attenuated infarct size and preserved LV function.
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Sarah
S
Chua
Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Steve
S
Leu
Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Jiunn-Jye
JJ
Sheu
Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Yu-Chun
YC
Lin
Basic Science, Nursing Department, Meiho University, Pingtung, Taiwan.
Li-Teh
LT
Chang
Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Ying-Hsien
YH
Kao
Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
Chia-Hung
CH
Yen
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Tzu-Hsien
TH
Tsai
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Yung-Lung
YL
Chen
Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Hsueh-Wen
HW
Chang
Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Cheuk-Kwan
CK
Sun
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Hon-Kan
HK
Yip