CHRONIC ISCHEMIC LEFT VENTRICULAR DYSFUNCTION

慢性缺血性左心室功能不全

基本信息

批准号：
6783316
负责人：
SANJIV KAUL
金额：
$ 28.52万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-01 至 2005-08-31
项目状态：
已结题

项目摘要

Chronic coronary artery disease is now the major cause of congestive heart failure (CHF) in the western hemisphere. With more people living longer, the incidence of CHF is rapidly on the rise. It is the commonest reason for repeated hospitalizations in the western hemisphere. Although novel ways to manage patients with ischemic CHF have evolved over the past decade, proper identification of patients who are potential candidates for these different treatment options is not performed optimally. The pathophysiology of chronic ischemic LV dysfunction is multifactorial involving previous infarction, post-ischemic dysfunction ('stunned myocardium'), or reduced resting MBF ('hibernating myocardium'), and more than one mechanism can be operative in any individual patient. Thus, the recognition of the specific substrate is very important from the point of view of treatment. We have recently developed a model of chronic ischemic LV systolic dysfunction where all these mechanisms are operative to different degrees. The overall aim of this research proposal is the noninvasive delineation of the mechanism(s) underlying LV systolic dysfunction in different myocardial segments within the same LV, and testing different management strategies for reversing this dysfunction. The studies will be performed in a canine model of chronic ischemic LV dysfunction with special emphasis on recognition of low-flow ischemia versus post-ischemic dysfunction versus non-ischemic dysfunction, and the individual therapeutic strategies for these various conditions. The specific aims of the research proposal are: 1. Accurate noninvasive identification of the specific pathophysiological basis for reduced wall thickening in each dysfunctional myocardial segment. 2. Effect of interventions on Ly dysfunction in relation to the underlying mechanism dysfunction. These interventions include: coronary artery bypass surgery and transmyocardial laser revascularization. 3. Effect of medical treatment in relation to the underlying cause of ischemic LV dysfunction. The drug we will test is carvedilol because of its unique adrenergic inhibitor properties as well as its anti-oxidant and anti-apoptotic properties.

慢性冠状动脉疾病现在是西半球充血性心力衰竭（CHF）的主要原因。随着人们寿命的延长，CHF 的发病率迅速上升。这是西半球反复住院的最常见原因。尽管在过去十年中已经出现了管理缺血性 CHF 患者的新方法，但尚未对这些不同治疗方案的潜在候选患者进行正确识别。慢性缺血性左心室功能障碍的病理生理学是多因素的，涉及先前的梗死、缺血后功能障碍（“心肌顿抑”）或静息MBF减少（“冬眠心肌”），并且不止一种机制可以在任何个体患者中发挥作用。因此，从治疗的角度来看，特定底物的识别非常重要。我们最近开发了一种慢性缺血性左心室收缩功能障碍的模型，其中所有这些机制都在不同程度上起作用。本研究提案的总体目标是无创地描述同一左心室不同心肌节段左心室收缩功能障碍的机制，并测试逆转这种功能障碍的不同管理策略。这些研究将在慢性缺血性左心室功能障碍的犬模型中进行，特别强调识别低流量缺血、缺血后功能障碍、非缺血性功能障碍，以及针对这些不同病症的个体治疗策略。该研究计划的具体目标是： 1. 准确无创地识别每个功能障碍心肌节段壁增厚减少的具体病理生理学基础。 2.干预措施对与潜在机制功能障碍相关的 Ly 功能障碍的影响。这些干预措施包括：冠状动脉搭桥手术和经心肌激光血运重建术。 3. 药物治疗对缺血性左心室功能障碍根本原因的影响。我们将测试的药物是卡维地洛，因为它具有独特的肾上腺素能抑制剂特性以及抗氧化和抗凋亡特性。