METABOLISM OF THE FAILING HEART

Our understanding of the pathogenesis and therapy of heart failure has evolved through three paradigms. Organ physiology, the first paradigm , focused therapy of heart failure on salt and water retention and vas oconstriction, which represent major circulatory responses to, cardiac pumping. The second paradigm of cell biochemistry led to the developm ent of powerful inotropic agents designed to increase myocardial contr actility. The third paradigm, gene expression (molecular biology), des cribes regulatory mechanisms that are both primitive and complex; in t he setting of heart failure, this paradigm focuses on the roles of alt ered myocardial cell growth and composition in explaining the accelera ted deterioration of the hypertrophied, failing heart. This review foc uses on one aspect of the second paradigm: factors that contribute to a state of energy-starvation and the resulting functional consequences in the failing heart.