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Am J Physiol Heart Circ Physiol 292: H1796-H1811, 2007. First published December 1, 2006; doi:10.1152/ajpheart.00784.2006
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Dynamic changes of cardiac conduction during rapid pacing

Aleksandar A. Kondratyev, Julien G. C. Ponard, Adelina Munteanu, Stephan Rohr, and Jan P. Kucera

Department of Physiology, University of Bern, Bern, Switzerland

Submitted 21 July 2006 ; accepted in final form 30 November 2006

Slow conduction and unidirectional conduction block (UCB) are key mechanisms of reentry. Following abrupt changes in heart rate, dynamic changes of conduction velocity (CV) and structurally determined UCB may critically influence arrhythmogenesis. Using patterned cultures of neonatal rat ventricular myocytes grown on microelectrode arrays, we investigated the dynamics of CV in linear strands and the behavior of UCB in tissue expansions following an abrupt decrease in pacing cycle length (CL). Ionic mechanisms underlying rate-dependent conduction changes were investigated using the Pandit-Clark-Giles-Demir model. In linear strands, CV gradually decreased upon a reduction of CL from 500 ms to 230–300 ms. In contrast, at very short CLs (110–220 ms), CV first decreased before increasing again. The simulations suggested that the initial conduction slowing resulted from gradually increasing action potential duration (APD), decreasing diastolic intervals, and increasing postrepolarization refractoriness, which impaired Na+ current (INa) recovery. Only at very short CLs did APD subsequently shorten again due to increasing Na+/K+ pump current secondary to intracellular Na+ accumulation, which caused recovery of CV. Across tissue expansions, the degree of UCB gradually increased at CLs of 250–390 ms, whereas at CLs of 180–240 ms, it first increased and subsequently decreased. In the simulations, reduction of inward currents caused by increasing intracellular Na+ and Ca2+ concentrations contributed to UCB progression, which was reversed by increasing Na+/K+ pump activity. In conclusion, CV and UCB follow intricate dynamics upon an abrupt decrease in CL that are determined by the interplay among INa recovery, postrepolarization refractoriness, APD changes, ion accumulation, and Na+/K+ pump function.

tachyarrhythmia; microelectrode arrays; conduction velocity; conduction block; mathematical modeling; integrative electrophysiology; cell culture; ventricular myocytes



Address for reprint requests and other correspondence: J. P. Kucera, Dept. of Physiology, Univ. of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland (e-mail: kucera{at}pyl.unibe.ch)




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A. Munteanu, A. A. Kondratyev, and J. P. Kucera
Analysis of Damped Oscillations during Reentry: A New Approach to Evaluate Cardiac Restitution
Biophys. J., February 1, 2008; 94(3): 1094 - 1109.
[Abstract] [Full Text] [PDF]




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