MYOCARDIAL ADAPTATION TO CORONARY OCCLUSION

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Our laboratory has developed a model of coronary collateral development in swine which results in a collateral dependent region of myocardium with little collateral vascular reserve even four months following coronary occlusion. Limited collateral vascular reserve is characteristic of humans with coronary artery disease. Past investigations using animal models of chronic coronary occlusion have dealt primarily with growth and development of the collateral circulation. Little information exist concerning the physiological characteristics and adaption of collateral dependent myocardium after chronic coronary artery occlusion. Studies in our laboratory in which antegrade reflow has been established to the collateral dependent myocardium distal to the coronary occlusion have shown significant changes in coronary hemodynamics in this region. We propose to further characterize the physiology of the collateral dependent myocardium 4 weeks to 1 year after placement of an ameroid-occluder on the proximal left circumflex coronary artery of swine. Anesthetized open- chest swine will be studied after antegrade coronary reflow is established to the collateral dependent myocardium distal to the ameroid occluder. Specifically we will 1) characterize the coronary hemodynamics of the collateral dependent region during antegrade reflow and examine arteriolar and capillary densities in this region post-mortem; 2) describe basal myocardial metabolism in the collateral dependent region by relating coronary blood flow, myocardial function, myocardial oxygen consumption and lactate production after antegrade reflow; 3) describe antegrade coronary blood flow, coronary vascular reserve and myocardial metabolism in collateral dependent myocardium during protocols which increase myocardial oxygen demand (i.e. dobutamine infusion) or decrease myocardial oxygen delivery (i.e. hypoxia) and; 4) determine which physiological alterations in the collateral dependent region persist six months to one year after coronary occlusion. These studies will provide important new information concerning myocardial adaptations occurring during chronic coronary occlusion.