The existence of a functional border zone (nonischemic muscle exhibiting dysfunction adjacent to an ischemic or infarcted area) is an important issue for the correct interpretation of most methods used clinically and experimentally to measure regional myocardial function. In our initial studies, we evaluated functional characteristics at the lateral margins of ischemic myocardium in anesthetized dogs. Circumflex artery occlusion produced nonischemic dysfunction extending 8 mm or 30 degrees of endocardial circumference from the perfusion boundary at one lateral margin. Although more limited in extent and severity than we had originally hypothesized, the data demonstrated that a functional border zone exists and that it may constitute an important feature in the overall impact on the left ventricle of acute regional ischemia. The main objective now is to characterize the functional border zone in conscious (rather than anesthetized) animals in order to evaluate nonischemic dysfunction chronically, up to 6 weeks after coronary occlusion. Systolic wall thickening proved to be a better functional parameter than segment shortening in earlier studies. Dogs will be chronically instrumented with sonomicrometers arrayed to provide high resolution measurements of wall thickness on both sides of the ischemic-nonischemic interface. Sigmoid curves will be fitted to the wall thickening data after occlusion to mathematically describe the distribution of functional impairment (and how it may change with time or different experimental interventions) across the perfusion boundary. The location of the perfusion boundary will be delineated with microspheres. Experiments are proposed to: 1. Establish the extent and severity of lateral nonischemic dysfunction in conscious dogs. 2. Determine if the functional border zone varies by location in the left ventricle. 3. Determine serial changes in lateral border zone function that may occur in the 4-6 weeks after myocardial infarction. 4. Evaluate changes that occur in viable subepicardial muscle overlying a subendocardial infarct.
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