The purpose of this research is to assess the response of the neonatal and infant human left ventricle to acute and chronic volume overload, using ventricular septal defect as a relatively pure model of preload stress. The effects of medical and surgical therapy will be measured, as well as long term outcome after surgical closure. Newly developed, sensitive indices of myocardial performance will be used to address these previous unexplored issues. Invasive and noninvasive indices of contractile state which are capable of distinguishing abnormalities of ventricular loading conditions from abnormal contractile state as well as diastolic indices of relaxation, filling, and myocardial compliance will be collected in a serial fashion during progression of the volume overload, before and after medical therapy, and before and after surgical closure to assess the following: (1) Serial changes during normal development in preload, afterload, contractile state, and diastolic function and abnormalities which result from volume overload. (2) The influence of medical and surgical interventions on ventricular mechanics in infants with VSD, and the effect of abnormalities on surgical recovery and late outcome. The patterns of wall stress, hypertrophy, and regression of hypertrophy in response to volume overload and its surgical therapy in infants. These data are needed to determine optimal medical therapy and to rationalize the timing and indications for surgical closure in infants with VSD's. In addition, as an excellent model system, these findings are applicable to more general issues concerning the effects of volume overload on the immature heart and the control of cardiac hypertrophy.
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