By applying new techniques of quantitative physiology, the studies of myocardial energetics and mechanics are proposed to provide insight into the pathophysiology of cardiac failure, as well as the ability to improve various interventions in the treatment of the failing heart. Using chronically implanted, conscious animals, the mechanisms of heart failure due to aortic stenosis, aortic regurgitation, mitral regurgitation, ventricular tachycardia, and global ischemia will be studied. Left ventricular energetics will be assessed using the new technique of thermodilution calorimetry and models relating myocardial oxygen consumption to mechanical energy or pressure-volume area. Ventriculo-arterial coupling will be examined to quantify ventricular load intrinsic and extrinsic to the ventricle itself. The major issues to be examined include the conditions under which the failing heart either wastes oxygen or consumes less oxygen. Others include the effects of various treatments for cardiac failure on left ventricular energetics, the effects of heart failure treatment on left ventricular mechanics, and the timing for such interventions as medical treatment or valve replacement to avoid irreversible changes in heart failure.
