The size of the current source to load mismatch determines the temporal evolution of intermittent conduction block across expansions of cardiac tissue during rapid pacing.

Aleksandar A. Kondratyev and Jan P. Kucera.

Dept. of Physiology, University of Bern , Bühlplatz 5, CH-3012 Bern , Switzerland.

It is known that expansions or branchings of cardiac tissue (e.g., in the border zone of infarct scars) represent sites of current source to load mismatch and form substrates for conduction block, a key ingredient of reentrant arrhythmias. It was the aim of this study to evaluate the evolution of intermittent conduction block across tissue expansions in patterned cultures of neonatal rat ventricular cells during rapid pacing, and to gain deeper insight into the ionic mechanisms of block using computer simulations.The patterned cultures consisted of cell strands (width: 40, 60 and 80 µm) expanding into large rectangular monolayers. The preparations were paced on the side of the strand for 1 min periods at a cycle length (CL) of 1000 ms alternating with 1 min periods at the shortest CL still resulting in 1:1 capture of the stimulus. Success or failure of conduction across the expansions was assessed by identifying cell contractions in digital videorecordings. Simulations were performed using a strand of 121 Luo-Rudy dynamic model cells releasing two 20-cell long branches from its center.In the cultures, the degree of conduction block (i.e., the percentage of blocked impulses) exhibited two distinct evolution patterns during the periods of rapid pacing. In all preparations with narrower strands (40 µm), the degree of block progressed as a function of time (from 23%±17% to 35%±11%, p<0.05, n=5), whereas, in all preparations with wider strands (60 and 80 µm), the degree of block regressed (from 30%±13% to 12%±9%, p<0.05, n=7). In the simulations, conduction exhibited a progressive deterioration: the conduction delay across the branch point increased progressively until 2:1 block occurred. This deterioration was caused by intracellular accumulation of Na+ and Ca2+, which led to a diminished driving force for inward currents and thus to a reduction of the current source.Therefore, intermittent conduction block across a tissue discontinuity can follow opposite evolutions depending on the size of the source to load mismatch. If this mismatch is large, the safety of conduction progressively decreases, possibly because of intracellular accumulation of Na+ and Ca2+. The mechanism underlying block regression in the presence of a smaller source to load mismatch remains however to be elucidated. In the diseased heart, these distinct evolutions will nevertheless be critical in determining the initiation, perpetuation and termination of reentry during tachyarrhythmic events.