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Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration.
Growth Factors ( IF 1.8 ) Pub Date : 2015-08-13
Evangelos P Daskalopoulos,Agapi D Vilaeti,Eleonora Barka,Polixeni Mantzouratou,Dimitrios Kouroupis,Marianthi Kontonika,Christos Tourmousoglou,Apostolos Papalois,Constantinos Pantos,W Matthijs Blankesteijn,Simeon Agathopoulos,Theofilos M Kolettis

Prevention of left ventricular remodeling is an important therapeutic target post-myocardial infarction. Experimentally, treatment with growth hormone (GH) is beneficial, but sustained local administration has not been thoroughly investigated. We studied 58 rats (322 ± 4 g). GH was administered via a biomaterial-scaffold, following in vitro and in vivo evaluation of degradation and drug-release curves. Treatment consisted of intra-myocardial injection of saline or alginate-hydrogel, with or without GH, 10 min after permanent coronary artery ligation. Echocardiographic and histologic remodeling-indices were examined 3 weeks post-ligation, followed by immunohistochemical evaluation of angiogenesis, collagen, macrophages and myofibroblasts. GH-release completed at 3 days and alginate-degradation at ∼7 days. Alginate + GH consistently improved left ventricular end-diastolic and end-systolic diameters, ventricular sphericity, wall tension index and infarct-thickness. Microvascular-density and myofibroblast-count in the infarct and peri-infarct areas were higher after alginate + GH. Macrophage-count and collagen-content did not differ between groups. Early, sustained GH-administration enhances angiogenesis and myofibroblast-activation and ameliorates post-infarction remodeling.

中文翻译:

持续给予心肌生长激素可减轻大鼠梗死后重塑。

预防左心室重塑是心肌梗死后的重要治疗目标。在实验上,用生长激素(GH)治疗是有益的,但是持续的局部给药尚未得到彻底研究。我们研究了58只大鼠(322±4 g)。在对降解和药物释放曲线进行体外和体内评估后,通过生物材料支架施用GH。治疗方法是在永久性冠状动脉结扎后10分钟,向心肌内注射生理盐水或藻酸盐水凝胶,有或没有GH。结扎后3周检查超声心动图和组织学重塑指数,然后对血管生成,胶原蛋白,巨噬细胞和成肌纤维细胞进行免疫组织化学评估。GH释放在3天时完成,藻酸盐降解在约7天时完成。海藻酸钠+ GH持续改善左心室舒张末期和收缩末期直径,心室球形度,壁张力指数和梗塞厚度。藻酸盐+ GH后,梗塞区和梗塞周区的微血管密度和成肌纤维细胞计数更高。两组之间的巨噬细胞计数和胶原蛋白含量没有差异。早期持续施用GH可增强血管生成和成纤维细胞活化,并改善梗死后重塑。
更新日期:2019-11-01
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