Description) Recent advances in +___________ our understanding of the fundamental processes involved in calcium regulation in the immature heart now provide the opportunity to develop rational, age-appropriate pharmacological strategies for altering cardiac performance. Studies from the investigator's laboratory have established that the primary calcium transport pathway in the late fetal and early newborn heart is the sarcolemmal sodium-calcium exchanger (NCX). The objective of this application is to exploit the predominant role of NCX as the primary target, either directly or indirectly, for modulation of contractile function in the immature heart. This represents an entirely new approach to the pharmacological manipulation of cardiac contractility during development. Experiments will be performed in freshly isolated ventricular myocytes at four different stages of development in rabbits. The investigator will also study ventricular myocytes isolated from human hearts in order to define critical aspects of regulation of contractile function during human maturation.
