Developmental changes in myocardial contractile responses to inotropic agents.

ABSTRACT

Although substantial information has accumulated over the past decade, many gaps remain in our understanding of the regulation of contractility and modulation of inotropic responsiveness in the developing heart. There are several important problems facing investigators in the field of developmental cardiology. Responses often differ among species and the human correlates to many of the animal studies remain to be defined. In many instances, the supply of tissues is limited and difficult to obtain consistently. Furthermore, comparable experiments may be nearly impossible to perform in human fetal and neonatal myocardium. Interpretation of results from developmental studies using various animal species and a number of different experimental models is further complicated by the complexity of normal developmental processes. Numerous changes are occurring simultaneously in neurohumoral influences, cardiac ultrastructure, protein synthesis, gene expression, and metabolism. Comprehensive integration of the impact of these and other factors on overall contractile performance and inotropic responsiveness requires a multifaceted approach incorporating a variety of techniques. Results from pharmacological experiments must be placed into perspective with available knowledge of relevant morphological, physiological, and biochemical status at the precise age in the particular species in which the experiments are performed. A thorough understanding of developmental cardiology is of more than simple academic interest. Basic knowledge of the regulation of contractile function during development will obviously have important therapeutic applications in the immature heart. Moreover, results from future developmental studies directed toward characterising myocardial gene expression, modulation of specific effector systems, and regulation of excitation-contraction coupling are ultimately likely to contribute to the design of therapeutic strategies for both congenital and acquired heart disease.