CHRONIC ISCHEMIC LEFT VENTRICULAR DYSFUNCTION

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。随着越来越多的人寿命延长，慢性心力衰竭的发病率正在迅速上升。这是西半球反复住院的最常见原因。尽管在过去的十年中，缺血性心力衰竭患者的治疗方法不断发展，但对这些不同治疗方案的潜在候选患者的正确识别并不是最佳的。慢性缺血性左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（“休克心肌”）或静息MBF减少（“冬眠心肌”），并且在任何个体患者中都可能存在不止一种机制。因此，从处理的角度来看，对特定基质的识别是非常重要的。我们最近开发了一种慢性缺血性左室收缩功能障碍模型，其中所有这些机制都在不同程度上起作用。本研究计划的总体目标是无创地描述同一左室不同心肌节段的左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。研究将在犬慢性缺血性左室功能障碍模型中进行，特别强调对低流量缺血、缺血后功能障碍和非缺血性功能障碍的识别，以及针对这些不同情况的个体治疗策略。研究计划的具体目的是：1。准确无创识别各功能不全心肌节段壁增厚减少的具体病理生理基础。2. 干预对Ly功能障碍的影响与潜在机制功能障碍有关。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. 药物治疗效果与缺血性左室功能障碍的根本原因有关。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细胞凋亡特性。

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.