The myocardium is a continually working aerobic organ. It is essential for normal myocardial function that a continual supply of oxygen is maintained to ensure a proper balance between myocardial oxygen supply and myocardial oxygen demands. The goal of this proposal is to investigate neural and microcirculatory mechanisms involved in regulating oxygen balance in the myocardium. Project I, Coronary Microvascular Dynamics, examines the hypothesis that the coronary microcirculation will exhibit a hierarchy of control to common stimuli. To accomplish Project I, I use a computer-controlled system which compensates for cardiac motion to enable microvascular pressure and diameter measurements in the beating heart. This computer-controlled device can move a micro-pipette in three dimensions in concert with a moving microvessel on a beating heart. Furthermore, using stroboscopic illumination (1 flash per heart cycle) microvessels are always in focus and """"""""appear"""""""" stationary. With this approach in the beating heart, there is little trauma to the coronary system and I can obtain continuous measurements of coronary microvascular pressures and diameters. The specific goals of the project are to answer the following questions: (1) What is the distribution of resistance in the coronary circulation of the left ventricle? (2) What are the changes in the distribution of resistance in the left ventricular coronary circulation during autoregulation? (3) What are the effects of neural stimulation or norepinephrine infusion on the distribution of resistance in the coronary circulation of the left ventricle? Project II, Adrenergic Control Mechanisms in the Coronary Circulation, tests the hypothesis that adrenergic vasoconstriction is augmented in models of coronary pathophysiology. This project entails measurement of myocardial perfusion with microspheres to innervated and sympathectomized regions of the left ventricle in conscious dogs. To accomplish this the posterior region of the left ventricular free wall is sympathectomized with phenol whereas the innervation of the anterior left ventricle remains intact. The specific goals of this project are to answer the following questions: (1) In the presence of a proximal coronary stenosis, what are the effects of the coronary sympathetic nerves on limiting coronary blood flow? (2) Are adrenergic coronary vasoconstrictor influences augmented in the coronary vascular system in animals with hypertension and left ventricular hypertrophy? (3) During exercise is perfusion to the right ventricle under greater sympathetic control than that to the left ventricle?
