Activation, Metabolism and Perfusion of the Heart

This paper presents combined experimental-theoretical results pertinent to anisotropic discontinuous propagation at a microscopic size scale «200 JJ.m). We first simulated how the transmembrane and extracellular potential waveforms, a.nd their derivatives, are theoretically related to each other and to the sodium current and conductance in normal propagating action potentials and at the site of a collision or end of a one-dimensional cable. We then applied the relationships between the time derivatives of the extracellular waveforms and the underlying action potentials in an experimental analysis of anisotropic propagation at this small size scale in human atrial muscle bundles of different ages. At sites where the boundary effects alter the rate of rise of the action potential, the time course of the internal membrane variables (gNa and INa) are changed in a way that alters the total open time of the sodium channels during depolarization. In turn, this predicts that the same concentration of sodium channel blocking drugs should have an anisotropic distribution in the depression of Vmax and conduction velocity, a prediction confirmed with preliminary experiments. The extracellular waveforms changed from a smooth contour during transverse propagation in young preparations to complex polyphasic waveforms in the older preparations. The differences in the extracellular waveforms and their derivatives indicated that there was electrical uncoupling of the side-to-side connections between small groups of fibers with aging. These changes produced a prominent zigzag course of transverse propagation at a microscopic level which, in turn, accounted for the marked complexity of the extracellular waveforms. The electrophysiological consequence was an age-related decrease in the 'effective' transverse conduction velocities to the range of very slow conduction which makes it possible for reentry to occur in small regions of cardiac muscle with normal cellular electrophysiological properties.