A Shift from Class I to Class III Drugs in the Medical Treatment of Arrhythmias: Wishful Thinking?

  • E. Carmeliet
Chapter

Abstract

Recently attention among clinicians and arthythmologists has shifted from the study of class I drugs acting on the Na+ channel to class III drugs or drugs prolonging the action potential duration. The immediate reason was the Cardiac Arrhythmia Suppression Trial (CAST) study (1989), which showed an increased mortality in patients treated for premature ventricular extrasystoles following myocardial infarction with drugs representative of the class I type [2]. The fundamental question that should be answered is whether better results may be expected from the new approach of using drugs prolonging the action potential duration. Is this new hope justified?

Keywords

Anisotropy Ischemia Manifold Lidocaine Dura 

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References

  1. 1.
    Campbell DL, Qu Y, Rasmusson RL, Strauss HC (1993) The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. II Closed state reverse use-dependent block by 4-aminopyridine. J Gen Physiol 101: 603–626Google Scholar
  2. 2.
    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: 406–412Google Scholar
  3. 3.
    Carlsson L, Abrahamsson C, Almgren O, Lundberg C, Duker G (1991) Prolonged action potential duration and positive inotropy induced by the novel class III antiarrhythmic agent H234/o9 (almokalant) in isolated human ventricular muscle. J Cardiovasc Pharmacol 18: 882–887PubMedCrossRefGoogle Scholar
  4. 4.
    Carmeliet E (1992) Voltage-and time-dependent block of the delayed K+ current in cardiac myocytes by dofetilide. J Pharmacol Exp Ther 262: 809–817PubMedGoogle Scholar
  5. 5.
    Carmeliet E (1993a) Use-dependent block and use-dependent unblock of the delayed rectifier K+ current by almokalant in rabbit ventricular myocytes. Circ Res 73:857–868Google Scholar
  6. 6.
    Carmeliet E (1993b) Use-dependent block of the delayed K+ current in rabbit ventricular myocytes. Cardiovasc Drugs Ther 7:599-604Google Scholar
  7. 7.
    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: 2235–2242PubMedCrossRefGoogle Scholar
  8. 8.
    Hondeghem LM (1991) Ideal antiarrhythmic agents: chemical defibrillators. J Cardiovasc Electrophysiol 2 [Suppl 1: S169 – S177Google Scholar
  9. 9.
    Hondeghem LM (1992) Development of class III antiarrhythmic agents. J Cardiovasc Pharmacol 20 [Suppl 21: S17 – S22CrossRefGoogle Scholar
  10. 10.
    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: 75–83Google Scholar
  11. 11.
    Opthof T, Coronel R, Vermeulen JT, Verberne HJ, van Capelle FJL, Janse MJ (1993) Dispersion of refractoriness in normal and ischaemic canine ventricle: effect of sympathetic stimulation. Cardiovasc Res 27:1954–1960 Google Scholar
  12. 12.
    Sanguinetti MC, Jurkiewicz NK (1990) Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol 96: 195–215Google Scholar
  13. 13.
    Starmer CF, Lastra AA, Nesterenko VV, Grant AO (1991) Proarhythmic response to sodium channel blockade. Theoretical model and numerical experiments. Circulation 84: 1364–1377Google Scholar

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© Springer-Verlag Berlin Heidelberg 1995

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  • E. Carmeliet

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