This proposal represents a continuation of studies of functional characteristics of the coronary vascular system which may influence perfusion of potentially ischemic myocardium. Studies will examine vasomotor characteristics of the coronary resistance vessels, both during unimpeded arterial inflow and in the presence of a flow-limiting stenosis, and of the collateral channels which supply myocardium distal to an occluded coronary artery. Studies will be performed in chronically instrumented dogs in which coronary artery flow is measured with an electromagnetic flowmeter and regional systolic shortening is assessed with ultrasonic microcrystals. Myocardial perfusion will be measured with microspheres while a coronary sinus catheter will allow measurement of myocardial oxygen extraction and lactate metabolism. Collateral vessel development will be induced by (1) embolizing a hollow plug into a coronary artery, (2) by use of the ameroid constrictor model, or (3) by repeated brief coronary occlusions. The following topics will be studied: (1) Does endogenously produced adenosine contribute to coronary vasodilation during exercise in the normal coronary circulation and when a proximal stenosis impedes arterial inflow? (2) Is there persistent residual vasodilator capacity of the resistance vessels when exercise in the presence of a coronary stenosis causes myocardial ischemia? Does pharmacologic vasodilation of the coronary resistance vessels during exercise in the presence of a coronary stenosis cause improved systolic function? Can further vasodilation of the resistance vessels cause undesirable effects, including a shift of blood flow away from the subendocardium or a passive increase in stenosis severity as the result of a decrease in coronary artery distending pressure? (3) Does cold exposure cause coronary vasoconstriction which opposes metabolic vasodilation produced by exercise in normally perfused myocardium or in the presence of a coronary stenosis? (4) Are the coronary collateral vessels capable of active vasoconstriction which may impair blood flow to the dependent myocardium in response to adrenergic stimuli or vasoactive peptides? (5) Is the marked variability of collateral vessel development in response to coronary artery occlusion related to differences in the degree of native collateral vascularity between animals? (6) Does chronic coronary artery occlusion cause an increase in the width of the perfusion boundary between adjacent normally perfused and collateral-dependent myocardial areas?
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