Optical recording of impulse propagation in designer cultures. Cardiac tissue architectures inducing ultra-slow...

It has long been established that slow conduction constitutes one of the key mechanisms in the generation of cardiac arrhythmias. Also, it has been recognized that alterations in the cellular architecture of cardiac tissue can contribute to slow conduction. Based on the recent development of an experimental system permitting both the design of geometrically defined cardiac tissue structures in culture and the measurement of impulse propagation at the cellular level, we investigated the extent of conduction slowing along a tissue structure consisting of a cell strand releasing multiple side branches. This structure, which can functionally be looked upon as a series of interconnected current-to-load mismatches, gave rise to ultra-slow conduction (1-2 cm/s) that displayed a high margin of safety due to a "pull" and "push" effect exerted by the side branches on electrotonic current flow along the main strand. Under physiological conditions, such branching structures might contribute to slow conduction in the AV-node and, under pathophysiological conditions, to the precipitation of reentrant arrhythmias within minuscule tissue regions in a structurally remodeled myocardium. The results illustrate that the combination of patterned growth techniques and optical recording of transmembrane voltage are ideally suited to characterize systematically the relationship between tissue structure and impulse conduction.