We propose to study the developmental changes in mammalian myocardium. Fetal, neonatal and adult myocardium will be studied both in vitro and in vivo to develop a basis for understanding changes with development and to determine when adult characteristics are acquired. These studies will be based on the hypothesis that describing these changes and how they come about will enable the mechanisms upon which adult myocardium functions to be fully elucidated. The description of sarcomere motion and force in the isolated preparation will provide a basis for explaining how sarcomere motion is transformed to force in the intact heart. The effect of changing the number and proportion of adrenergic receptors in the developing myocardium on the myocardial responses to adrenergic agonists is not well described. The exploration of these responses will allow the functional effect of developmental changes in adrenergic receptors to be described and ultimately applied to understanding how the acquisition of receptors is coupled to post-receptor responses and in the clinical utilization of sympathomimetic drugs for poor ventricular function in the neonate and child. The effect of in utero cardiovascular lesions on the time course of developmental changes in contractility will be monitored in order to determine if and in what manner the normal time courses are altered and whether and in what manner the achieved mechanical characteristics differ from the adult ones. These results will be of value in understanding how hypertrophy, both with normal development and pathologic lesions, alters cardiac function and how the elimination of the lesions will allow cardiac function to return to normal. These insights should lead to a better understanding of myocardial performance under normal and abnormal work loads and so provide the basis for useful and new diagnostic methods in evaluating not only the infant and the child but also the adult.
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