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，CHF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，治疗缺血性充血性心力衰竭患者的新方法已经发展，但正确地确定哪些患者是这些不同治疗方案的潜在候选者并没有得到最佳的执行。慢性缺血性左心功能不全的病理生理学机制是多因素的，包括既往脑梗塞、缺血后功能障碍(“顿抑心肌”)或静息MBF减少(“冬眠心肌”)，任何一个患者都可以有多种机制可供手术治疗。因此，从治疗的角度来看，对特定底物的识别非常重要。我们最近开发了一种慢性缺血性左心室收缩功能障碍的模型，所有这些机制都在不同程度上起作用。这项研究的总体目标是无创性地描述同一左室内不同心肌节段左室收缩功能障碍的机制(S)，并测试不同的治疗策略来逆转这种功能障碍。这些研究将在慢性缺血性左心功能障碍的犬模型中进行，特别强调识别低流量缺血与缺血后功能障碍与非缺血功能障碍，以及针对这些不同情况的个体化治疗策略。该研究方案的具体目的是：1.准确无创性地确定各功能不全心肌节段减少室壁增厚的具体病理生理学基础。2.干预对Ly功能障碍与潜在机制功能障碍的影响。这些干预措施包括：冠状动脉搭桥术和激光心肌血运重建术。3.治疗对缺血性左心功能不全根本原因的影响。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。

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.