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

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*

*Corresponding author for this work

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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 similar to 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.
Original languageEnglish
Pages (from-to)250-258
JournalGrowth Factors
Volume33
Issue number4
DOIs
Publication statusPublished - 2015

Keywords

  • Alginate
  • angiogenesis
  • growth hormone
  • myofibroblasts
  • myocardial infarction
  • ventricular remodeling

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