The primary aim is to test an hypothesis concerning the effects of nonuniform compressive and tangential ventricular wall stresses on the balance between oxygen supply and demand in different regions of the myocardium under normal and various abnormal hemodynamic conditions. The approach will be to obtain biochemical data on regional myocardial metabolism and indicator uptake data on regional myocardial blood flow in a canine open chest preparation in which the conditions of proximal coronary artery stenosis and segmental coronary artery occlusion can be stimulated, and in a domestic swine preparation in which the condition of left ventricular hypertrophy due to a chronic pressure overload can be simulated. A number of hemodynamic and metabolic variables will be measured, including left ventricular, coronary and aortic pressures, total myocardial blood flow and oxygen consumption, and the myocardial tissue levels of creatine phosphate, adenosine triphosophate, and lactate. The tissue analysis will be performed on the outer, middle, and inner thirds of a transmural sample procured in situ from the beating left ventricle. Additional tissue analysis for biochemical indices of regional left ventricular hypertrophy will be obtained in the pressure overloaded swine heart. It is hoped that the proposed project will provide information on the nutritional adequacy of regional myocardial flow under a variety of physiological conditions, and new insights into the pathophysiology of subendocardial ischemia, myocardial infarction, and the mechanism of cardiac hypertrophy.
NIH ExPorter
NIH ExPorter