Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

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 function at the area of infarct in the pig. Methods: Myocardial infarction was induced in 12 female anaesthetized 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 mu g . kg(-1) in two animals and 0.6 mu g . 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 was st (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 significantly 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 peri-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 number in both groups (P=0.8), as were mesenchymal cells stained for vimentin (P=0.7). Conclusions: Exogenous IGF-II delivered to the infarct ai ea ameliorates regional cardiac function in the pig, perhaps by inducing peri-infarct myocyte growth.