Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Jan;108(1):255–261. doi: 10.1111/j.1476-5381.1993.tb13471.x

Effects of hyperkalaemia on the depression of maximum rate of depolarization by class I antiarrhythmic agents in guinea-pig myocardium.

K R Wyse 1, V Ye 1, T J Campbell 1
PMCID: PMC1907716  PMID: 8428209

Abstract

1 Standard microelectrode methods were used to record intracellular action potentials from strips of guinea-pig right ventricular myocardium superfused with either standard physiological saline ([K+] = 5.6 mM) or the same solution modified to contain [K+] = 11.2 mM. 2 The effects on action potential parameters of three therapeutic concentrations of mexiletine, quinidine and disopyramide were studied under both conditions at four different drive rates (interstimulus intervals = 2400, 1200, 600 and 300 ms). 3 Hyperkalaemia in the absence of drugs produced reductions in resting potential (-86.7 +/- 2.5 mV to -71.8 +/- 3.7 mV; n = 30; P < 0.001), maximum rate of depolarization (300 +/- 46.5 V s-1 to 205.6 +/- 37.6 V s-1; P < 0.0001), and action potential duration (205 +/- 26 ms to 188 +/- 32 ms; P < 0.05). 4 All three drugs produced increased depression of maximum rate of depolarization in hyperkalaemia compared to control conditions, but at all three concentrations this enhancement of effect was greater for mexiletine than for quinidine, with disopyramide exhibiting intermediate behaviour. 5 Mexiletine behaved very similarly to therapeutic concentrations of lignocaine as described in previous reports from this laboratory. 6 Quinidine behaved very similarly to Class Ic agents. 7 It is concluded that mexiletine demonstrated significantly greater selectivity for depolarized myocardium than quinidine and that this may have implications in terms of proarrhythmic potential. 8 Disopyramide exhibited intermediate selectivity for depolarized myocardium between mexiletine and quinidine.

Full text

PDF
255

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arif M., Laidlaw J. C., Oshrain C., Willis P. W., 3rd, Nissen C. H., McDermott D. J., Smith W. S., Karim A., Wilson R. R. A randomized, double-blind, parallel group comparison of disopyramide phosphate and quinidine in patients with cardiac arrhythmias. Angiology. 1983 Jun;34(6):393–400. doi: 10.1177/000331978303400603. [DOI] [PubMed] [Google Scholar]
  2. Brugada J., Boersma L., Kirchhof C., Allessie M. Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias. Circulation. 1991 Oct;84(4):1808–1818. doi: 10.1161/01.cir.84.4.1808. [DOI] [PubMed] [Google Scholar]
  3. Campbell N. P., Pantridge J. F., Adgey A. A. Long-term oral antiarrhythmic therapy with mexiletine. Br Heart J. 1978 Jul;40(7):796–801. doi: 10.1136/hrt.40.7.796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Campbell T. J., Hemsworth P. D. Selective depression of maximum rate of depolarization of guinea-pig ventricular action potentials by amiodarone and lignocaine in simulated ischaemia: comparison with encainide. Clin Exp Pharmacol Physiol. 1990 Feb;17(2):135–145. doi: 10.1111/j.1440-1681.1990.tb01296.x. [DOI] [PubMed] [Google Scholar]
  5. Campbell T. J. Kinetics of onset of rate-dependent effects of Class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Cardiovasc Res. 1983 Jun;17(6):344–352. doi: 10.1093/cvr/17.6.344. [DOI] [PubMed] [Google Scholar]
  6. Campbell T. J. Proarrhythmic actions of antiarrhythmic drugs: a review. Aust N Z J Med. 1990 Jun;20(3):275–282. doi: 10.1111/j.1445-5994.1990.tb01039.x. [DOI] [PubMed] [Google Scholar]
  7. Campbell T. J., Wyse K. R., Hemsworth P. D. Effects of hyperkalemia, acidosis, and hypoxia on the depression of maximum rate of depolarization by class I antiarrhythmic drugs in guinea pig myocardium: differential actions of class Ib and Ic agents. J Cardiovasc Pharmacol. 1991 Jul;18(1):51–59. doi: 10.1097/00005344-199107000-00008. [DOI] [PubMed] [Google Scholar]
  8. Coplen S. E., Antman E. M., Berlin J. A., Hewitt P., Chalmers T. C. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation. 1990 Oct;82(4):1106–1116. doi: 10.1161/01.cir.82.4.1106. [DOI] [PubMed] [Google Scholar]
  9. Denes P., Gabster A., Huang S. K. Clinical, electrocardiographic and follow-up observations in patients having ventricular fibrillation during Holter monitoring. Role of quinidine therapy. Am J Cardiol. 1981 Jul;48(1):9–16. doi: 10.1016/0002-9149(81)90566-x. [DOI] [PubMed] [Google Scholar]
  10. Echt D. S., Liebson P. R., Mitchell L. B., Peters R. W., Obias-Manno D., Barker A. H., Arensberg D., Baker A., Friedman L., Greene H. L. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991 Mar 21;324(12):781–788. doi: 10.1056/NEJM199103213241201. [DOI] [PubMed] [Google Scholar]
  11. Hoffman B. F., Rosen M. R., Wit A. L. Electrophysiology and pharmacology of cardiac arrhythmias. VII. Cardiac effects of quinidine and procaine amide. A. Am Heart J. 1975 Jun;89(6):804–808. doi: 10.1016/0002-8703(75)90197-0. [DOI] [PubMed] [Google Scholar]
  12. Hondeghem L. M. Antiarrhythmic agents: modulated receptor applications. Circulation. 1987 Mar;75(3):514–520. doi: 10.1161/01.cir.75.3.514. [DOI] [PubMed] [Google Scholar]
  13. Jackman W. M., Friday K. J., Anderson J. L., Aliot E. M., Clark M., Lazzara R. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis. 1988 Sep-Oct;31(2):115–172. doi: 10.1016/0033-0620(88)90014-x. [DOI] [PubMed] [Google Scholar]
  14. Morganroth J., Anderson J. L., Gentzkow G. D. Classification by type of ventricular arrhythmia predicts frequency of adverse cardiac events from flecainide. J Am Coll Cardiol. 1986 Sep;8(3):607–615. doi: 10.1016/s0735-1097(86)80190-5. [DOI] [PubMed] [Google Scholar]
  15. Morganroth J. Comparative efficacy and safety of oral mexiletine and quinidine in benign or potentially lethal ventricular arrhythmias. Am J Cardiol. 1987 Dec 1;60(16):1276–1281. doi: 10.1016/0002-9149(87)90608-4. [DOI] [PubMed] [Google Scholar]
  16. Morganroth J. Early and late proarrhythmia from antiarrhythmic drug therapy. Cardiovasc Drugs Ther. 1992 Feb;6(1):11–14. doi: 10.1007/BF00050910. [DOI] [PubMed] [Google Scholar]
  17. Morganroth J., Goin J. E. Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias. A meta-analysis. Circulation. 1991 Nov;84(5):1977–1983. doi: 10.1161/01.cir.84.5.1977. [DOI] [PubMed] [Google Scholar]
  18. Morganroth J., Horowitz L. N. Flecainide: its proarrhythmic effect and expected changes on the surface electrocardiogram. Am J Cardiol. 1984 Feb 27;53(5):89B–94B. doi: 10.1016/0002-9149(84)90509-5. [DOI] [PubMed] [Google Scholar]
  19. Morganroth J. Risk factors for the development of proarrhythmic events. Am J Cardiol. 1987 Apr 30;59(11):32E–37E. doi: 10.1016/0002-9149(87)90199-8. [DOI] [PubMed] [Google Scholar]
  20. Morganroth J., Somberg J. C., Pool P. E., Hsu P. H., Lee I. K., Durkee J., Salerno D. M. Comparative study of encainide and quinidine in the treatment of ventricular arrhythmias. J Am Coll Cardiol. 1986 Jan;7(1):9–16. doi: 10.1016/s0735-1097(86)80251-0. [DOI] [PubMed] [Google Scholar]
  21. Niarchos A. P. Disopyramide: serum level and arrhythmia conversion. Am Heart J. 1976 Jul;92(1):57–64. doi: 10.1016/s0002-8703(76)80403-6. [DOI] [PubMed] [Google Scholar]
  22. Vaughan Williams E. M. Subgroups of class 1 antiarrhythmic drugs. Eur Heart J. 1984 Feb;5(2):96–98. doi: 10.1093/oxfordjournals.eurheartj.a061632. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES