The ultimate objective of the proposed research is to characterize and quantify basic cellular electrophysioloigcal properties of the developing myocardium. It is hoped that an analysis of this information will provide an understanding of the dynamic relationship between the maturation of cardiac cellular processes, and the response of the myocardium to ischemia, hypoxia, and acidosis. A comprehensive study of the changes in cellular membrane currents, ionic fluxes, and excitation-contraction coupling processes that accompany growth appears to be a prerequisite to understanding the differences in electrophysiological and mechanical properties of neonatal and adult hearts. Although there is evidence suggesting that certain intrinsic electrophysiological and mechanical properties of heart muscle may be age-dependent, many difficulties have surrounded efforts to quantitatively analyze these properties. These problems have arisen because of the technical complexity of adapting standard quantitative techniques to the smaller, more fragile neonatal tissue. However, it now appears that newer methods of examining isolated heart mescle may obviate the technical difficulties that have quantitative data and meaningful comparisons of neontal and adult ardiac tissues. The proposed investigation will utilize the voltage clamp technique and preparations to quantitatively elucidate developmental changes in cellular ionic fluxes. Furthermore, a study will be undertaken of the age-related changes in the response of these variables to hypoxia, ischemia, and acidosis. Integration of this data will provide insight into the cellular electrophysiological and mechanical effects of hypoxia and ischemia on the developing myocardium.
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