Skip to main content
SpringerLink
Log in

Rate Dependence of Antiarrhythmic and Proarrhythmic Properties of Class I and Class III Antiarrhythmic Drugs

  • Conference paper
Monophasic Action Potentials

Abstract

Rate or frequency dependence is a characteristic property of antiarrhythmic drugs belonging to the Vaughan William classes I and III [1]. The class I action, for instance, conduction slowing or QRS widening is more pronounced at faster rates. This reflects the intrinsic rate dependence of sodium channel blockade induced by these drugs. The sodium channel block increases with faster rates [2]. Likewise, the antiarrhythmic effect can be attributed to an increasing prolongation of the functional refractory period but may also be due to conversion of a unidirectional into a bidirectional block of conduction [3,4].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Vaughan Williams EM (1989) Classification of Anti-arrhythmic Agents. Springer, Berlin Heidelberg New York

    Google Scholar 

  2. Heistracher P (1971) Mechanisms of action of antifibrillatory drugs. Naiinyn Schmiedebergs Arch Pharmacol 269:199–212

    Article  CAS  Google Scholar 

  3. Antoni H (1971) Electrophysiological mechanisms underlying pharmacological models of cardiac fibrillation. Pflugers Arch 269:177–199

    CAS  Google Scholar 

  4. Weirich J, Antoni H (1986) Vulnerability of the heart to ventricular fibrillation:basic mechanisms. In:Rupp H (ed) Regulation of heart function. Basic concepts and clinical applications. Thieme, New York, pp 376–396

    Google Scholar 

  5. Carmeliet E (1992) Voltage- and time-dependent block of the delayed K+ current in cardiac myocytes by dofetilide. J Pharmacol Exp Ther 262:809–817

    PubMed  CAS  Google Scholar 

  6. Yang T, Snyders DJ, Roden DM (1995) Ibutilide, a methanesulfonaanilide, is a potent blocker of the rapidly activating delayed rectifier K+ current (IKr) in AT-1 cells. Concentration-, time-, voltage-, and use-dependent effects. Circulation. 91 (6):1799–1806

    PubMed  CAS  Google Scholar 

  7. Tande PM, Bjornstad H, Yang T, Refsum H (1990) Rate-dependent class III antiarrhythmic action, negative chronotropy, and positive inotropy of a novel IK blocking drug, UK- 68–798:potent in guinea pig but no effect in rat myocardium. J Cardiovasc Pharmacol 16:401–410

    Article  PubMed  CAS  Google Scholar 

  8. Hondeghem LM, Snyders DJ (1990) Class III antiarrhythmic agents have a lot of potential but a long way to go. Circulation 81:686–690

    Article  PubMed  CAS  Google Scholar 

  9. Weirich J, Hohnloser S, Antoni H (1994) d-Sotalol and dofetilide exhibits slow offset kinetics:significance for their antifibrillatory efficacy. Pace 17(II):332

    Google Scholar 

  10. Weirich J, Bernhardt R, Loewen N, Wenzel W, Antoni H (1996) Regional- and Species- Dependent Effects of K+ Channel Blocking Agents on Subendocardium and Mid-Wall Slices of Human, Rabbit and Guinea Pig Myocardium. Pflugers Arch 431 [Suppl]:328

    Google Scholar 

  11. Gintant GA (1996) Two components of delayed rectifier current in canine atrium and ventricle. Does IKs play a role in the reverse rate dependence of class III agents ? Circ Res 78:26–37

    PubMed  CAS  Google Scholar 

  12. Colatsky TJ, Follmer CH, Starmer CF (1990) Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias. Circulation 82:2235–2242

    Article  PubMed  CAS  Google Scholar 

  13. Eisenberg RS (1990) Channels as enzymes. J Membrane Biol 115:1–12

    Article  CAS  Google Scholar 

  14. Unwin N (1989) The structure of ion channels in membranes of excitable cells. Neuron 3:665–676

    Article  PubMed  CAS  Google Scholar 

  15. Hille H (1992) Mechanisms of block. In:Hille H (ed) Ionic channels of excitable membranes. Sinauer, Sunderland, MA, pp 376–396

    Google Scholar 

  16. Charnet etal. (1990) An open-channel blocker interacts with adjacent turns of a-helices in the nicotinic acetylcholine receptor. Neuron 2:87–95

    Article  Google Scholar 

  17. Ragsdale DS, McPhee JC, Scheuer T, Catteral WA (1994) Molecular determinants of state- dependent block of Na+ channels by local anesthetics. Science 265:1724–1728

    Article  PubMed  CAS  Google Scholar 

  18. Starmer CF, Grant AO, Strauss HC (1984) Mechanisms of use-dependent block of sodium channels in excitable membranes by local anesthetics. Biophys J 46:15–27

    Article  PubMed  CAS  Google Scholar 

  19. Hondeghem LM, Katzung BG (1977) Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium-channels. Biochim Biophys Acta 472:373–398

    PubMed  CAS  Google Scholar 

  20. Starmer CF (1986) Theoretical characterization of ion channel blockade:ligand binding to periodically accessible receptors. J Theor Biol 119:235–249

    Article  PubMed  CAS  Google Scholar 

  21. Weirich J, Antoni H (1989) Modelling frequency- and voltage-dependent effects of a class I antiarrhythmic drug (nicainoprol) on Vmax of the cardiac action potential from guinea- pig papillary muscle. Naunyn Schmiedebergs Arch Pharmacol 340:456–464

    Article  PubMed  CAS  Google Scholar 

  22. Weirich J (1992) Frequency-dependent action of antiarrhythmic drugs:the useful concept of periodical ligand binding. Basic Res Cardiol 8:205–214

    Article  Google Scholar 

  23. Weirich J, Antoni H (1990) Differential analysis of the frequency-dependent effects of class I-antiarrhythmic drugs according to periodical ligand binding:implications on antiarrhythmic and proarrhythmic efficacy. J Cardiovasc Pharmacol 15:998–1009

    Article  PubMed  CAS  Google Scholar 

  24. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators (1989) Preliminary report:effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 321:406–412

    Google Scholar 

  25. Weirich J, Hohnloser SH, Antoni H (1992) Differential analysis of frequency-dependent effects of antiarrhythmic drugs:importance of the saturation behavior of frequency- dependent sodium-channel blockade. J Cardiovasc Pharmacol 20 [Suppl 2]:8–16

    Article  Google Scholar 

  26. Jurkiewicz NK, Sanguinetti MC (1993) Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circ Res 72:75–83

    PubMed  CAS  Google Scholar 

  27. Li GR, Feng J, Yue L, Carrier M, Nattel S (1996) Evidence for two components of the delayed rectifier K+ current in human ventricular myocytes. Circ Res 78:689–696

    PubMed  CAS  Google Scholar 

  28. Luo CH, Rudy Y (1991) A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. Circ Res 68:1501–1526

    PubMed  CAS  Google Scholar 

  29. Zeng J, Laurita KR, Rosenbaum DS, Rudy J (1995) Two components of the delayed rectifier K+ current in ventricular myocytes of the guinea pig type. Circ Res 77:140–152

    PubMed  CAS  Google Scholar 

  30. Carmeliet E (1993) Use-dependent block of the delayed K+ current in rabbit ventricular myocytes. Cardiovasc Drugs Ther 7:599–604

    Article  PubMed  Google Scholar 

  31. Yang T, Roden DM (1996) Extracellular potassium modulation of drug block of IKr. Implications for torsades de pointes and reverse use-dependence. Circulation 93:407–411

    PubMed  CAS  Google Scholar 

  32. anuary CT, Riddle JM, Salata J J (1988) A model for early afterdepolarizations:induction with Ca-channel antagonist Bay K 8644. Circ Res 72:75–83

    Google Scholar 

  33. Jackman WM, Friday KJ, Anderson JL, Aliot EM, Clark M (1988) The long QT syndromes:a crtical review, new clinical observations and unifying hypothesis. Prog Cardiovasc Dis 31:115–172

    Article  PubMed  CAS  Google Scholar 

  34. Weirich J, Bernhardt R, Posival H, Minami K, Antoni H (1995) Differential class-3 effects of dofetilide on human, rabbit, and guinea-pig ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol 351:401

    Google Scholar 

  35. Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu F, Towbin JA Keating MT, Hammoude H, Brown AM, Chen LS, Colatsky TJ (1995) Long QT-syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation 92:3381–3386

    PubMed  CAS  Google Scholar 

  36. Liu D, Antzelevitch C (1995) Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell. Circ Res 76:351–365

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Jörg Weirich
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Cardiology, Veterans Affairs Medical Center and Georgetown University, 50 Irving St NW, 20422, Washington, DC, USA

    Michael R. Franz M.D., Ph.D. (Prof. of Med.) (Prof. of Med.)

  2. Elektrophysiologisches Labor, Deutsches Herzzentrum München, Lazarettstraße 36, 80636, München, Germany

    Claus Schmitt  & Bernhard Zrenner  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Weirich, J. (1997). Rate Dependence of Antiarrhythmic and Proarrhythmic Properties of Class I and Class III Antiarrhythmic Drugs. In: Franz, M.R., Schmitt, C., Zrenner, B. (eds) Monophasic Action Potentials. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60851-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60851-3_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64585-3

  • Online ISBN: 978-3-642-60851-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation