Copyright © 1995 by the European Society of Cardiology.
© 1995 The European Society of Cardiology
Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine
The Neufeld Cardiac Research Institute, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University Tel Aviv, Israel
*The Department of Pathology, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University Tel Aviv, Israel
Kabi-Pharmacia Stockholm, Sweden
The Goldschleger Eye Research Institute, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University Tel Aviv, Israel
revised 9 March 1995; accepted 26 April 1995.
Correspondence: Alexander Battler, MD, Director, Cardiology Division, Soroka Medieal Center, Beer Sheva, Israel 84105
Abstract
OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocyte growth and contractility in vitro. This study was designed to investigate the effect of exogenous IGF-II on regional myocardial fun ction at the area of infarct in the pig.
METHODS: Myocardial infarction was induced in 12 female anoesthetized pigs by affigel blue beads, embolizing microvessels of the left anterior descending coronary artery distribution. In the experimental group (n=6), IGF-II (0.12 µg. kg–1 in two animals and 0.6 µg. kg–1 in four) was incorporated into the beads and delivered by them to the infarct area. Myocardial function was followed echocardiographically, and the excised heart was analysed immunohistochemically and histopathologically.
RESULTS: Myocardial function in injured zones, inversely related to an echocardiographic segmental wall motion score (mean ± SEM), was similar between the two groups at baseline, but at 4 weeks post-infarction was significantly (P=0.008) reduced in the control group (0.58± 0.38 vs 3.42 ± 0.84), in contrast to nearly baseline values in the experimental group (0.58 ± 0.33 vs 1.17 ± 0.42, P=0.41). Cardiac performance in injured segments was sign better after myocardial injury in the experimental group (P=0.04). Tissue samples from both groups (4 weeks post-infarction), stained with haematoxylin and eosin demonstrated pen-infarct myocyte hypertrophy, corresponding to regions selectively stained by an antibody for CD56, which highlights growing cardiac myocytes. By image analysis semi-quantification, staining for CD56 was significantly (P=0.04) higher in the peri-infarct region of the experimental group, as compared with controls (106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvessels stained for von-Willebrand factor were similar in nwnber in both groups (P=0.8), as were mesenchymal cells stained for vimentin (P=0.7).
CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area ameliorates regional cardiac function in the pig, perhaps by inducing peri-infarct myocyte growth.
Key Words: Insulin-like growth factor II • pig • myocardial infarction • echocardiography • hypertrophy • CD-56 • microembolization • infarction
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