CORONARY COLLATERAL FUNCTION

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The long term objectives are to characterize changes in coronary collateral function and elucidate mechanisms responsible for coronary collateral development under conditions of progressively improving collateral function without infarction. Studies will be performed in the conscious pony subjected to a regimen of intermittent coronary artery occlusions to stimulate collateral function. The animal will be instrumented with a Doppler flow probe and pneumatic occluder on the left anterior descending coronary artery, ultrasonic dimension gauges for measuring myocardial segment function, and chronically implanted catheters in the left atrium, LAD, and anterior cardiac vein. Use of this animal model permits long term observations on myocardial blood flow, metabolism, and segment function in a repeatedly ischemic, collateral dependent region of myocardium. Questions concerning the optimal intermittent coronary occlusion regimen, the anatomical distribution of mature collaterals, and the progression of changes in 1) the size and shape of the underperfused region, 2) myocardial norepinephrine release, 3) collateral conductance, and 4) the opening behavior of maturing and functionally regressed collateral vessels will be examined. The role of regional ischemia versus the inter-coronary artery pressure gradient as the primary stimulus for collateralization will also be investigated. Finally, an analysis of coronary venous blood draining the collateral dependent region for endothelial cell growth factors and other potential angiogenesis factors will be performed at different stages of collateral development. This work should help establish a promising new animal model for coronary and cardiac research, and provide original findings on the stimulus and behavior of maturing coronary collateral vessels relevant to the understanding and treatment of coronary heart disease.