CORONARY MICROVASCULAR RESPONSES TO HUMORAL SUBSTANCES

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The objective of this proposal is to assess vasomotor responses of both native and mature collateral arteries and arterioles in vivo to neurohumoral and physiological stimuli by directly visualizing collateral microvessels on the left ventricle of the dog. Collateral microvessels on the epicardium will be visualized using two techniques. First, respiratory-induced motion is minimized using high frequency jet ventilation synchronized to the heart cycle. Second, motion of the heart due to contraction will be compensated for using computer-controlled stroboscopic epi-illumination synchronized to the cardiac cycle. Stroboscopic illumination visually freezes the motion of the heart enabling visualization of the microcirculation with a microscopic-video digitizing system. Thus, in an unrestrained heart vasomotor responses of microvessels from 30 to 400 micromoles can be measured. Microvascular pressures will be obtained using a computer-controlled electromechanical micropipette holder and the servo-null technique. Collaterals will be visually traced between the left anterior descending and left circumflex arteries using fluorescence angiography. Responses to both native and stimulated collaterals will be measured to test the hypothesis that the response of both native and stimulated collaterals to neurohumoral and physiological stimuli will be dependent upon the initial vessel size similar to non-collateral vessels. It is only with these techniques to visualize the coronary microcirculation that vasomotor responses of collaterals can be directly measured in vivo. The specific aims to be addressed in this proposal are: 1) to determine the response of both native and stimulated collaterals to vasodilators (nitroglycerin, acetylcholine) and vasoconstrictors (serotonin, endothelin, vasopressin and PGF2alpha.); 2) to determine the response of native collaterals to decreases in perfusion pressure and the vasodilator reserve with nitroglycerin or adenosine of collaterals in the presence of a flow-limiting stenosis or total occlusion; 3) to determine whether the response of native collaterals to serotonin is augmented in the presence of a flow-limiting stenosis or total coronary occlusion; and 4) to determine the distribution of microvascular pressures in native and mature collaterals and the distribution of microvascular resistance in myocardium dependent upon stimulated collaterals.