Angeli Franca S, Shapiro Mia, Amabile Nicolas, Orcino Gina, Smith Charles S, Tacy Theresa, Boyle Andrew J, Chatterjee Kanu, Glantz Stanton A, Grossman William, Yeghiazarians Yerem
Division of Cardiology, Department of Medicine, University of California, San Francisco, California, USA.
Comp Med. 2009 Jun;59(3):272-9.
Current guidelines recommend beta blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a beta blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure-volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dt(max)), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential beta coefficient of the LV end-diastolic pressure-volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% +/- 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia-reperfusion swine model of acute MI on beta-blocker therapy and may guide future studies.
当前指南推荐心肌梗死(MI)患者使用β受体阻滞剂。心力衰竭的新型疗法在进入临床试验之前,应与这种药物联合进行测试。在这项方法学研究中,我们试图描述在用β受体阻滞剂治疗的猪MI闭胸模型中,心脏收缩和舒张功能参数在6周时间内的变化过程。通过对10头猪的左前降支冠状动脉进行90分钟的球囊闭塞来诱导心肌梗死。在心肌梗死前以及心肌梗死后1周和6周收集超声心动图和压力-容积数据;在6周时评估组织病理学。在6周内,左心室(LV)容积显著增加,射血分数、壁运动指数、每搏功、压力上升速率(dP/dt(max))、可募集前负荷每搏功和机械效率显著降低。舒张功能障碍表现为左心室舒张末压力-容积关系的指数β系数显著增加以及左心室压力衰减减少。在6周时,组织病理学分析显示梗死面积大小为16.3%±4.4%,与未梗死猪(n = 5)相比,梗死边缘和远隔区域的左心室质量和心肌细胞横截面积均增加。这些发现提示在β受体阻滞剂治疗的急性心肌梗死闭胸缺血-再灌注猪模型中,随着时间推移存在动态的重塑模式,并可能为未来的研究提供指导。