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.
J Inflamm (Lond). 2012 Jun 1;9(1):21. doi: 10.1186/1476-9255-9-21.
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.
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.
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).
Intra-coronary administration of tacrolimus significantly attenuated infarct size and preserved LV function.
我们通过结扎小型猪的左前降支冠状动脉来测试以下假说，即在急性心肌梗死（AMI）后通过冠状动脉内给予他克莫司是否可以限制梗死面积并保存左心室射血分数（LVEF）。
将 12 只雄性小型猪随机分为 AMI-盐水（MI-only）组和 AMI-他克莫司（MI-Tac）组，在结扎后 30 分钟分别给予冠状动脉内注射盐水（3.0ml）和他克莫司（0.5mg 于 2.5ml 盐水中）。
MI-only 组的梗死面积更大（p<0.001）。MI-only 动物的蛋白水平 [氧化应激、肿瘤坏死因子-α、核因子-κB]、基因（基质金属蛋白酶-9、纤溶酶原激活物抑制剂-1）和细胞水平（CD40+、CD68+炎症细胞）的炎症生物标志物显著升高（p<0.01）。相反，抗炎生物标志物在基因水平（白细胞介素-10）、基因和蛋白水平（内皮型一氧化氮合酶）以及基因和蛋白水平的抗氧化生物标志物 [血红素加氧酶 1、NAD(P)H：醌氧化还原酶]均降低（p<0.01）。MI-only 组的细胞凋亡核数量和基因及蛋白水平的凋亡生物标志物表达（Bax、caspase 3）显著升高，而基因和蛋白水平的抗凋亡生物标志物（Bcl-2）、LVEF 和分数缩短显著降低（p<0.001）。
冠状动脉内给予他克莫司可显著减轻梗死面积并保存 LV 功能。
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