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Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine purkinje fibres

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Summary

The cellular electrophysiological effects of restacorin, a new antiarrhythmic agent were studied using conventional microelectrode techniques in isolated dog cardiac Purkinje fibres. Restacorin (1 – 30 µmol/l) decreased the maximum rate of rise of the action potential upstroke and action potential amplitude while action potential duration measured at 90% of repolarization was shortened in a concentration-dependent manner during pacing at a constant basic cycle length of 500 ms. The effect of 10 µmol/l restacorin on maximal rate of rise of the action potential upstroke and on action potential duration measured at 90% of repolarization were also studied while varying the constant pacing cycle length between 300 and 5000 ms. The results of these studies indicated a rate-dependent effect of restacorin on the action potential characteristics examined. After abrupt changes in cycle length, 10 µmol/l restacorin slowed the fast component of the relation for restitution of action potential duration from 155.3 ± 5.2 ms (control, n = 6) to 217.1 ± 17.8 ms (n = 6, P < 0.05). In the presence of restacorin (10 µmol/l), a second slow component for recovery of maximal action potential up stroke rising velocity was expressed having a time constants of 8.5 ± 1.2 s. The range of premature action potential durations was significantly decreased (by 57.1%, P < 0.01) by 10 µmol/l restacorin. These results indicate that the cellular electrophysiological effects produced by restacorin in dog cardiac Purkinje fibres best resemble those produced by recognized class Ic antiarrhythmic drugs.

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Authors and Affiliations

  1. Departments of Pediatrics, University of Cincinnatti College of Medicine, Cincinnatti, OH, USA

    Andràs Varrò, Timothy K. Knilans, Péter P. Nànàsi & David A. Lathrop

  2. Departments of Pharmacology and Cell Biophysics, University of Cincinnatti College of Medicine, Cincinnatti, OH, USA

    Andràs Varrò & David A. Lathrop

  3. Institute for Drug Research, Budapest, Hungary

    Andràs Varrò & György Rabloczkys

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  1. Andràs Varrò
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  2. Timothy K. Knilans
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  3. Péter P. Nànàsi
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  4. György Rabloczkys
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  5. David A. Lathrop
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Varrò, A., Knilans, T.K., Nànàsi, P.P. et al. Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine purkinje fibres. Naunyn-Schmiedeberg's Arch Pharmacol 342, 691–697 (1990). https://doi.org/10.1007/BF00175714

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  • DOI: https://doi.org/10.1007/BF00175714

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