Zhang Pei, Li Tielou, Griffith Bartley P, Wu Zhongjun J
Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, Md., USA.
Cells Tissues Organs. 2015;200(5):349-62. doi: 10.1159/000435875. Epub 2015 Aug 14.
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.
存活心肌最初会代偿心肌梗死（MI）后受损心肌的损失，并逐渐出现功能障碍。关于梗死面积对进行性心肌重构过程中心肌时空变化的影响，相关研究有限。在绵羊梗死模型中制造了三种梗死面积的MI，即左心室（LV）壁的15%、25%和35%。研究了12周内LV的进行性重构。进行了超声心动图、超声测微术以及组织学和分子分析，以评估心脏功能、局部组织收缩功能、结构重构、心肌细胞肥大以及钙处理蛋白。MI后12周，15%、25%和35%MI组的LV舒张末期标准化容积分别为1.4±0.2、1.7±0.3和2.0±0.4 ml/kg，收缩末期标准化容积分别为1.0±0.1、1.0±0.2和1.3±0.3 ml/kg，LV射血分数分别为43±3%、42±6%和34±4%。它们均与假手术组不同（p<0.05）。与梗死灶远端的心肌相比，所有三个MI组在梗死灶相邻心肌中均表现出更大的壁面积扩张（重构应变）、更大的心肌细胞大小以及钙处理蛋白表达改变。在相邻区域，心肌细胞大小与重构应变之间存在显著相关性。三个MI组之间的比较分析表明，更大的梗死面积（35%MI与15%MI相比）与更大的重构应变、区域组织水平上细胞结构和组成的更严重损伤以及局部收缩功能和器官水平上的LV功能损伤相关。
