title: Multiscale Characterization of Impact of Infarct Size on Myocardial Remodeling in an Ovine Infarct Model.
abstract: The surviving myocardium initially compensates the loss of injured myocardium after myocardial infarction (MI) and gradually becomes progressively dysfunctional. There have been limited studies on the effect of infarct size on temporal and spatial alterations in the myocardium during progressive myocardial remodeling. MI with three infarct sizes, i.e. 15, 25 and 35% of the left ventricular (LV) wall, was created in an ovine infarction model. The progressive LV remodeling over a 12-week period was studied. Echocardiography, sonomicrometry, and histological and molecular analyses were carried out to evaluate cardiac function, regional tissue contractile function, structural remodeling and cardiomyocyte hypertrophy, and calcium handling proteins. Twelve weeks after MI, the 15, 25 and 35% MI groups had normalized LV end diastole volumes of 1.4 ± 0.2, 1.7 ± 0.3 and 2.0 ± 0.4 ml/kg, normalized end systole volumes of 1.0 ± 0.1, 1.0 ± 0.2 and 1.3 ± 0.3 ml/kg and LV ejection fractions of 43 ± 3, 42 ± 6 and 34 ± 4%, respectively. They all differed from the sham group (p < 0.05). All the three MI groups exhibited larger wall areal expansion (remodeling strain), larger cardiomyocyte size and altered expression of calcium handing proteins in the adjacent myocardium compared to the remote counterpart from the infarct. A significant correlation was found between cardiomyocyte size and remodeling strain in the adjacent zone. A comparative analysis among the three MI groups showed that a larger infarct size (35 vs. 15% MI) was associated with larger remodeling strain, more serious impairment in the cellular structure and composition, and regional contractile function at regional tissue level and LV function at organ level.
authors.affiliation: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, Md., USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Tielou
authors.initials: T
authors.lastname: Li
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
authors.forename: Zhongjun J
authors.initials: ZJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000473:pathology*; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D012756:Sheep; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*