A MODEL OF CHRONIC ISCHEMIC HEART FAILURE

慢性缺血性心力衰竭模型

• 批准号: 3346907
• 负责人: ADRIAN KANTROWITZ
• 金额: $ 5.57万
• 依托单位: VIADERM, LLC
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1986-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346907
• 关键词: catheterization; cineangiocardiography; collateral circulation; disease /disorder model; electrocardiography; electrodes; heart circulation; heart failure; heart function; heart pharmacology; heart ventricle; histopathology; model design /development; myocardial ischemia /hypoxia; thrombosis

The purpose of the proposed research is to investigate the role of discretionary, sequential electrothrombogenesis (ETG) in the creation of a practical model of chronic (3-month) ischemic left ventricular failure. Nearly all reported models either accomplish too little--the heart undergoes no lasting change--or too much--the animal dies. In the proposed technique 8 electrodes whose ends will be exteriorized will be implanted in the lumina of left coronary artery branches in each of 60 dogs. In 25 conscious dogs that have recovered from thoracotomy (Group A), anodal current will be applied to the LAD near its origin for 6 hours to induce a thrombus (i.e., electrothrombogenesis, or ETG). After the dog's recovery, branches of the circumflex (CX) will be obstructed by ETG one by one until the pulmonary capillary wedge pressure (PCWP) is greater than 15 mm Hg. The dog will then be kept in failure for 3 months, receiving medical treatment when the PCWP is greater than 20 mm Hg. Documentation of the dog's response to each ETG will include cardiac output and PCWP measurement during graded treadmill exercise, and standard clinical observations. Left coronary cineangiography will be performed after recovery from thoracotomy and just before sacrifice. Comparison of left ventricular function curves and evaluation of clinical data will define the most practical protocol. The same procedure will be followed in 25 Group B animals, except that the first ETG will be applied to the CX and succeeding ones to the branches of the LAD. Five Group C dogs will serve as controls. A simplified protocol will be developed on the basis of the Group A and B results and followed in 5 Group D dogs to confirm its practicality. Since the dog represents the most difficult case for establishment of a chronic failure model, the protocol, if successful, is expected to be readily transferred to larger species, such as those used in study of mechanical circulatory assist devices.

这项研究的目的是调查 自由裁量权，顺序电血栓形成（ETG）在创建一个 慢性（3个月）缺血性左心室衰竭的实用模型。 几乎所有报告的模型要么完成太少-心脏 没有持续的变化--或者变化太大--动物就会死亡。 拟议 技术8将其末端将被外置的电极植入 60只犬左冠状动脉分支管腔。 在25 开胸术后恢复的清醒犬（A组）， 电流将被施加到靠近其原点的LAD 6小时，以诱导 血栓（即，电血栓形成或ETG）。 狗康复后， 回旋支（CX）的分支将被ETG一个接一个地阻塞， 肺毛细血管楔压（PCWP）大于15 mm Hg。 这只狗将被关在失败的3个月，接受医疗 当PCWP大于20 mm Hg时进行治疗。 记录本 犬对每个ETG的反应将包括心输出量和PCWP测量 在分级跑步机运动和标准临床观察期间。 左 开胸术后恢复后行冠状动脉造影 就在献祭之前 左心室功能曲线的比较 临床数据的评估将确定最实用的方案。 在25只B组动物中遵循相同程序，不同之处在于 第一个ETG将应用于CX，随后的ETG将应用于 LAD。 C组5只犬作为对照。 简化协议 将在A组和B组结果的基础上制定， D组5只犬，以确认其实用性。 由于狗代表了建立一个最困难的情况下， 慢性失效模型，该方案如果成功， 容易转移到较大的物种，如用于研究 机械循环辅助装置。