Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice
Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice
复制标题
DOI：
10.1161/01.cir.99.23.3063
复制
发表时间：
1999-06-15
期刊：
影响因子：
37.8
通讯作者：
Lee, RT
中科院分区：
文献类型：
--
作者：
Rohde, LE;Ducharme, A;Lee, RT
细胞外基质的合成和降解有助于心肌梗死（MI）后发生的形态学变化。方法和结果：我们验证了基质金属蛋白酶（MMPs）抑制可减轻实验性心肌梗死左心室重构的假设。71只左前冠状动脉结扎术后存活的雄性FVB小鼠随机分为广谱MMP抑制剂（cp - 471474）和安慰剂组，通过灌胃。在随机化前（手术24小时内）和4天后进行超声心动图研究，包括在乳头中部和根尖水平的短轴成像。根据壁运动异常定义的梗死在79%的手术中发生（n = 56）， 4天治疗期间的死亡率为23%（治疗组36例中有9例，安慰剂组35例中有7例；P = NS），治疗组和安慰剂组舒张末期和收缩末期的基线尺寸和面积相似（P = NS）。在随访中，与分配给安慰剂的梗死小鼠相比，分配给MMP抑制剂的梗死小鼠在收缩末期和舒张末期的尺寸和乳头中部和根尖水平的面积的增加明显较小
Background-Extracellular matrix synthesis and degradation contribute to the morphological changes that occur after myocardial infarction (MI).Methods and Results-We tested the hypothesis that inhibition of matrix metalloproteinases (MMPs) attenuates left ventricular remodeling in experimental MI. Seventy-one male FVB mice that survived ligation of the left anterior coronary artery were randomized to a broad-spectrum MMP inhibitor (CP-471,474) or placebo by gavage. Echocardiographic studies were performed before randomization (within 24 hours of surgery) and 4 days later and included short-axis imaging at the midpapillary and apical levels. Infarction as defined by wall motion abnormality was achieved in 79% of the procedures (n = 56), and mortality rate during the 4-day protocol was 23% (9 of 36 on treatment vs 7 of 35 on placebo; P = NS), Baseline end-diastolic and end-systolic dimensions and areas were similar (P = NS) between treated and placebo groups. At follow-up, infarcted mice allocated to MMP inhibitor had significantly smaller increases in end-systolic and end-diastolic dimensions and areas at both midpapillary and apical levels compared with infarcted mice allocated to placebo (all P