The long-term objective of this project is to determine to what extent the rate and pattern of propagation in the mammalian heart depend upon the morphological substratum. Developing cardiac muscle will be used since, in a short period of time and yet asynchronously, several structural changes occur which affect axial resistance; this asynchronicity enables one to find cases where only a single morphological parameter is changing over a given period. For each preparation at each age, propagation velocity along and across the long axes of the cells of the right atrium and ventricle will be determined by extracellular recording, and indices of membrane properties (amplitude, maximum rate of rise, and time constant of foot of action potential, resting potential) will be determined by intracellular recording. Morphologic and morphometric techniques will be used to determine cell surface-to-volume ratio, cell length, cell diameter, cell volume, extracellular space annulus, nexus area-to-cell volume ratio, sarcomere length and septation index. Where there is a change in either longitudinal or transverse propagation velocity (or their ratio) as well as a single significant structural change, it will be possible to relate that structural change to the functional change. In this way, the effects of (1) cardiomyocyte geometry, (2) distribution of cardiomyocyte interconnections, and (3) subdivision of the myocardial mass into interconnecting fascicles and bundles upon propagation velocity and pattern will be discovered. Such data are important since the types of structural changes seen during development (e.g., in cell diameter, nexal coupling, and extent of septation) are seen in pathologic states and in normal ageing, and may contribute to arrhythmogenesis in those conditions.
