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.
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