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.

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

Acknowledgements

The skillful technical assistance of Lily Vervoort-Peters (Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands) in the immunohistochemistry experiments is gratefully acknowledged. We thank Prof H. Stamatis and Dr M. Katsoura (Department of Biological Applications and Technology, University of Ioannina, Greece) for their help in fluorescence measurements. We also thank Eleftheria Karampela, Nikolaos Psychalakis, Kalliopi Tsarea, Maria Karamperi and Antonios Karaiskos (Experimental Research Center ELPEN, Pikermi, Athens, Greece) and Anastasia Fambri (medical student at the University of Ioannina) for their valuable help during the experiments. The animal care provided by Stergios Gerakis and Evripidis Gerakis (Experimental Research Center ELPEN, Pikermi, Athens, Greece) is gratefully acknowledged. Eleni Goga (Cardiovascular Research Institute, Ioannina and Athens, Greece) efficiently coordinated this research.

Declaration of interest

The authors report no declarations of interest.