Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration

Abstract

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.