CHRONIC ISCHEMIC LEFT VENTRICULAR DYSFUNCTION

慢性缺血性左心室功能不全

• 批准号: 6650862
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/6650862
• 关键词: angiogenesis; antiadrenergic agents; antihypertensive agents; antioxidants; biomechanics; chronic disease /disorder; congestive heart failure; coronary bypass; coronary disorder; dogs; heart contraction; heart function; heart pharmacology; heart ventricle; hemodynamics; histopathology; immunocytochemistry; myocardial infarction; myocardial ischemia /hypoxia; myocardium; tissue /cell culture

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。随着更多的人寿命更长，CHF的发生率迅速上升。 这是西半球反复住院的最常见原因。 尽管在过去的十年中，管理缺血性CHF患者的新型方法已经发展，但对这些不同治疗选择的潜在候选患者的适当识别并未最佳地进行。 慢性缺血性LV功能障碍的病理生理是多因素的，涉及先前的梗塞，缺血后功能障碍（“震惊的心肌”）或静息MBF（“冬眠心肌'）以及任何患者的静息MBF（“冬眠性心肌”）可以操作。 因此，从治疗的角度来看，对特定底物的识别非常重要。 我们最近开发了一个慢性缺血性LV收缩功能障碍的模型，其中所有这些机制在不同程度上都可以操作。这项研究建议的总体目的是对同一LV内不同心肌段中基础LV收缩功能障碍的机制的无创划分，并测试了反向这种功能障碍的不同管理策略。 这些研究将在慢性缺血性LV功能障碍的犬模型中进行，特别强调低流量缺血与缺血后功能障碍与非缺血性功能障碍的识别，以及在各种情况下的单个治疗策略。研究建议的具体目的是：1。对每个功能失调的心肌段降低壁增厚的特定病理生理基础的准确无创鉴定。 2。与潜在机制功能障碍有关的干预措施对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跨膜激光血运重建。 3。与缺血性LV功能障碍的根本原因有关的医疗作用。 我们将测试的药物是卡维地醇，因为它具有独特的肾上腺素抑制剂及其抗氧化剂和抗凋亡特性。