Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine |
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Authors: | BATTLER A; HASDAI D; GOLDBERG I; OHAD D; DI SEGNI E; BOR A; VARDA-BLOOM N; VERED Z; KORNOWSKI R; LAKE M; NASS D; SAVION N |
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Institution: | 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 |
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Abstract: | OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0.12 µg. kg1 in two animalsand 0.6 µg. kg1 in four) was incorporated intothe beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0.008) reducedin 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). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0.04). Tissue samples fromboth groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0.04) higher in the peri-infarctregion of the experimental group, as compared with controls(106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvesselsstained for von-Willebrand factor were similar in nwnber inboth groups (P=0.8), as were mesenchymal cells stained for vimentin(P=0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth. |
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Keywords: | Insulin-like growth factor II pig myocardial infarction echocardiography hypertrophy CD-56 microembolization infarction |
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