Edwards Richard, Yousef Zaheer, Rakhit Roby, Wright Mathew, Rosenthal Eric, Redwood Simon, Marber Michael
Deparment of Cardiology, KCL, Guy's, King's and St. Thomas' School of Medicine, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, Great Britain.
Basic Res Cardiol. 2002 Sep;97(5):374-83. doi: 10.1007/s003950200046.
Coronary artery ligation is the standard technique to induce regional myocardial infarction in small animal models. However, opening the chest and incising the pericardium independently influence post-MI remodelling. Our purpose was to develop and characterize a novel closed chest model of regional myocardial infarction (MI) in the rabbit of increased clinical relevance. Coronary angiography was performed percutaneously in New Zealand White Rabbits (NZW) using pre-formed catheters. A 0.36 mm thrombogenic coil was positioned in the circumflex artery to induce closed chest MI. Of rabbits undergoing coil deployment 40 % survived until day 100. Rabbits were classified as small MI (n = 5), moderate MI (n = 6) and large MI (n = 6) < 15 %, 15 - 30 %, > 30 % of LV myocardial volume respectively) or sham controls (n=11). Transthoracic echocardiographic images were obtained 0, 3, 5, 7, 14, 28, 60, 100 days post procedure. At day 100, LVEDP was measured before and after plasma substitute infusion. Hearts were subsequently excised and chamber stiffness (Kc) was derived from the passive pressure-volume relationship. Cardiac weight, dimensions and MI as a percentage of LV volume (MI%) were also recorded. Differences in percentage fractional shortening (%FS) were apparent from day 14. %FS was reduced in rabbits with large and moderate MI compared to controls (day 100, p < 0.005 and p < 0.05, respectively). LVEDP was increased in large and moderate MI compared to small MI and controls (26 mmHg +/- 6 and 21 mmHg +/- 5 vs. 9 mmHg +/- 1 and 7 mmHg +/- 3 p < 0.005); these differences were maintained during plasma substitute infusion. Kc in large MI was significantly less than moderate MI, small MI or control (all p < 0.05). Direct morphometric measurements distinguished between all groups.This study provides the first description of post-infarction remodelling after coronary artery occlusion where the pericardium remains intact in a small animal model. We believe it may provide a more physiologically and clinically relevant in vivo assay system of left ventricular dysfunction after myocardial infarction.
冠状动脉结扎是在小动物模型中诱导局部心肌梗死的标准技术。然而，打开胸腔和切开心包会独立影响心肌梗死后的重塑过程。我们的目的是开发并描述一种在兔身上建立的具有更高临床相关性的新型闭合胸腔局部心肌梗死（MI）模型。使用预制导管对新西兰白兔（NZW）进行经皮冠状动脉造影。将一个0.36毫米的致血栓形成线圈放置在回旋动脉中以诱导闭合胸腔心肌梗死。在接受线圈植入的兔子中，40%存活至第100天。兔子被分为小面积心肌梗死组（n = 5）、中等面积心肌梗死组（n = 6）和大面积心肌梗死组（n = 6）（分别为左心室心肌体积的<15%、15 - 30%、>30%）或假手术对照组（n = 11）。在术后0、3、5、7、14、28、60、100天获取经胸超声心动图图像。在第100天，在输注血浆代用品前后测量左心室舒张末期压力（LVEDP）。随后取出心脏，从被动压力 - 容积关系中得出心室僵硬度（Kc）。还记录了心脏重量、尺寸以及心肌梗死面积占左心室体积的百分比（MI%）。从第14天起，左心室短轴缩短率（%FS）的差异就很明显。与对照组相比，大面积和中等面积心肌梗死的兔子%FS降低（第100天，分别为p < 0.005和p < 0.05）。与小面积心肌梗死组和对照组相比，大面积和中等面积心肌梗死组的LVEDP升高（26 mmHg ± 6和21 mmHg ± 5 vs. 9 mmHg ± 1和7 mmHg ± 3，p < 0.005）；在输注血浆代用品期间这些差异持续存在。大面积心肌梗死组的Kc明显低于中等面积心肌梗死组、小面积心肌梗死组或对照组（所有p < 0.05）。直接形态测量法区分了所有组。本研究首次描述了在小动物模型中心包保持完整的冠状动脉闭塞后梗死后期的重塑过程。我们认为它可能为心肌梗死后左心室功能障碍提供一个在生理和临床方面更相关的体内检测系统。
