Intra-coronary administration of tacrolimus markedly attenuates infarct size and preserves heart function in porcine myocardial infarction

Journal of Inflammation

Research

Li-Teh Chang¹  Steve Leu²  Chia-Hung Yen³  Hsueh-Wen Chang⁴  Cheuk-Kwan Sun⁵  Ying-Hsien Kao⁶  Yu-Chun Lin⁶  Yung-Lung Chen⁷  Sarah Chua⁷  Tzu-Hsien Tsai⁷  Hon-Kan Yip⁸  Jiunn-Jye Sheu⁹ 

[1] Basic Science, Nursing Department, Meiho University, Pingtung, Taiwan;Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan;Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan;Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan;Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan;Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;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;Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;

关键词: Tacrolimus;    Left Ventricular Ejection Fraction;    Acute Myocardial Infarction;    Left Anterior Descend;    Infarct Area;   

DOI  :  10.1186/1476-9255-9-21

 received in 2011-12-18, accepted in 2012-06-01,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundWe 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.MethodsTwelve 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.ResultsLarger 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).ConclusionIntra-coronary administration of tacrolimus significantly attenuated infarct size and preserved LV function.

【 授权许可】

Unknown   
© Chua et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.