Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration.
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.
a Department of Pharmacology , Cardiovascular Research Institute Maastricht, Maastricht University , Maastricht , The Netherlands .|b Cardiovascular Research Institute , Ioannina , Athens , Greece .
Evangelos P
EP
Daskalopoulos
b Cardiovascular Research Institute , Ioannina , Athens , Greece .
Agapi D
AD
Vilaeti
b Cardiovascular Research Institute , Ioannina , Athens , Greece .|c Ceramics and Composites Laboratory, Department of Materials Science and Engineering, University of Ioannina , Ioannina , Greece .
Eleonora
E
Barka
d Department of Pharmacology , Medical School, University of Athens , Athens , Greece .
Polixeni
P
Mantzouratou
e Department of Biomedical Research, Foundation for Research and Technology-Hellas , Institute of Molecular Biology and Biotechnology , Ioannina , Greece , and.
Dimitrios
D
Kouroupis
b Cardiovascular Research Institute , Ioannina , Athens , Greece .
Marianthi
M
Kontonika
b Cardiovascular Research Institute , Ioannina , Athens , Greece .
Christos
C
Tourmousoglou
b Cardiovascular Research Institute , Ioannina , Athens , Greece .|f Experimental Research Center ELPEN , Pikermi , Athens , Greece.
Apostolos
A
Papalois
d Department of Pharmacology , Medical School, University of Athens , Athens , Greece .
Constantinos
C
Pantos
a Department of Pharmacology , Cardiovascular Research Institute Maastricht, Maastricht University , Maastricht , The Netherlands .
W Matthijs
WM
Blankesteijn
c Ceramics and Composites Laboratory, Department of Materials Science and Engineering, University of Ioannina , Ioannina , Greece .
Simeon
S
Agathopoulos
b Cardiovascular Research Institute , Ioannina , Athens , Greece .
Theofilos M
TM
Kolettis
D000464:Alginates / Q000737:chemistry; D000818:Animals; D020723:Glucuronic Acid / Q000737:chemistry; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D009203:Myocardial Infarction / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds / Q000737:chemistry; D020257:Ventricular Remodeling
D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D013006:Growth Hormone
Alginate; angiogenesis; growth hormone; myocardial infarction; myofibroblasts; ventricular remodeling