Pathologic conditions such as hypertension and valvular herat disease impose a sustained excessive load on the heart. In response to this abnormal hemodynamic burden, the heart adapts by a pattern of hypertrophic growth which is concentric for a pressure overload and eccentric for a volume overload. This alteration in mass and configuration enables the heart to maintain systemic perfusion despite an excessive circulatory load that would acutely exceed the capacity of the normal heart. However, one of the major problems in clinical cardiology is that the hypertrophied heart is often not able to chronically sustain this increased load and congestive heart failure supervenes. The overall objectives of this proposal are to determine the extent to which ventricular dimensions and morphology are critical for the transition from stable ventricular hypertrophy to ventricular dysfunction and failure and to determine, once ventricular dysfunction occurs, whether amelioration of the inciting hemodynamic burden will reverse the depression of ventricular performance and the changes in morphology associsated with cardiac hypertrophy and failure. Ventricular performance will be assessed in several models of genetic and experimentally-porduced systemic hypertension and volume overload in rats to determine the level and duration of the hemodynamic burden that produces left ventricular dysfunction. Basal and stressed hemodynamics, passive left ventricular pressure-volume relations, and echocardiographic indices of ventricular dimensions will be assessed at various ages in these models of overload. Ventricular performance will then be related to morphologic determinations of myocyte size and subcellular composition to determine whether ventricular dysfunction is associasted with a critical imbalance between cellular components and volume. Measurements of geometry and calculations of wall stresses will be made in left ventricles with compensated hypertrophy and hypertrophy with dysfunction to determine whether the increasing internal load imposed by an expanded ventricular diameter may eventually exceed the initial benefit of a reduction in the fiber shortening required to maintain stroke volume and lead to cardiac decompensation. Our final objective is to determine whether, once ventricular dysfunction is evident, amelioration of the inciting hemodynamic load will reverse cardiac decompensation or whether the altered ventricular geometry and morphology will sustain dysfunction.