Electrophysiological Mechanisms for the Antiarrhythmic Action of Mexiletine on Digitalis-, Reperfusion- and Reoxygenation-induced Arrhythmias

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1985 Dec 1

PMID 4075017

Citations 6

Authors

S Amerini

P Carbonin

E Cerbai

A GIOTTI

A Mugelli

M Pahor

Affiliations

Soon will be listed here.

Abstract

The antiarrhythmic potency of mexiletine was evaluated on three groups of guinea-pig isolated hearts. Arrhythmias were induced (a) with digitalis intoxication, (b) with hypoxia followed by reoxygenation and (c) with ischaemia followed by reperfusion. Mexiletine 10 microM was found to be very effective against all three types of arrhythmias in all three groups. The electrophysiological effects of mexiletine were then studied on sheep cardiac Purkinje fibres manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin. Mexiletine 10 microM consistently decreased the amplitude of oscillatory afterpotentials and blocked subsequent triggered activity in sheep Purkinje fibres. In contrast, mexiletine 10 microM had no significant effect on Vmax in normal, barium- and strophanthidin-treated preparations. The results are discussed in relation to the mechanisms of antiarrhythmic action of mexiletine.

Citing Articles

Relevance of mexiletine in the era of evolving antiarrhythmic therapy of ventricular arrhythmias.

Alhourani N, Wolfes J, Konemann H, Ellermann C, Frommeyer G, Guner F Clin Res Cardiol. 2024; 113(6):791-800.

PMID: 38353682 PMC: 11108884. DOI: 10.1007/s00392-024-02383-9.

Electrophysiological mechanism for the antiarrhythmic action of propafenone: a comparison with mexiletine.

Amerini S, Bernabei R, Carbonin P, Cerbai E, Mugelli A, Pahor M Br J Pharmacol. 1988; 95(4):1039-46.

PMID: 3219479 PMC: 1854270. DOI: 10.1111/j.1476-5381.1988.tb11737.x.

Role of calcium ions in reperfusion arrhythmias: relevance to pharmacologic intervention.

Opie L, Coetzee W Cardiovasc Drugs Ther. 1988; 2(5):623-36.

PMID: 3154637 DOI: 10.1007/BF00054202.

Mexiletine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias.

Monk J, Brogden R Drugs. 1990; 40(3):374-411.

PMID: 2226221 DOI: 10.2165/00003495-199040030-00005.

Lack of correlation between the antiarrhythmic effect of L-propionylcarnitine on reoxygenation-induced arrhythmias and its electrophysiological properties.

Barbieri M, Carbonin P, Cerbai E, Gambassi Jr G, LO GIUDICE P, Masini I Br J Pharmacol. 1991; 102(1):73-8.

PMID: 2043933 PMC: 1917891. DOI: 10.1111/j.1476-5381.1991.tb12134.x.

References

Allen J, Ekue J, Shanks R, Zaidi S . The effect of Kö 1173, a new anticonvulsant agent on experimental cardiac arrhythmias. Br J Pharmacol. 1972; 45(4):561-73. PMC: 1665959. DOI: 10.1111/j.1476-5381.1972.tb08114.x. View

Di Gennaro M, Carbonin P, Vassalle M . On the mechanism by which caffeine abolishes the fast rhythms induced by cardiotonic steroids. J Mol Cell Cardiol. 1984; 16(9):851-62. DOI: 10.1016/s0022-2828(84)80009-7. View

Ferrier G . Digitalis arrhythmias: role of oscillatory afterpotentials. Prog Cardiovasc Dis. 1977; 19(6):459-74. DOI: 10.1016/0033-0620(77)90010-x. View

Kass R, Lederer W, Tsien R, Weingart R . Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978; 281:187-208. PMC: 1282691. DOI: 10.1113/jphysiol.1978.sp012416. View

Kass R, Tsien R, Weingart R . Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978; 281:209-26. PMC: 1282692. DOI: 10.1113/jphysiol.1978.sp012417. View

Penkoske P, Sobel B, Corr P . Disparate electrophysiological alterations accompanying dysrhythmia due to coronary occlusion and reperfusion in the cat. Circulation. 1978; 58(6):1023-35. DOI: 10.1161/01.cir.58.6.1023. View

Attwell D, Cohen I, Eisner D, Ohba M, Ojeda C . The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch. 1979; 379(2):137-42. DOI: 10.1007/BF00586939. View

Vassalle M, Lin C . Effect of calcium on strophanthidin-induced electrical and mechanical toxicity in cardiac Purkinje fibers. Am J Physiol. 1979; 236(5):H689-97. DOI: 10.1152/ajpheart.1979.236.5.H689. View

Sheridan D, Penkoske P, Sobel B, Corr P . Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats. J Clin Invest. 1980; 65(1):161-71. PMC: 371351. DOI: 10.1172/JCI109647. View

10.

Tsien R, Kass R, Weingart R . Cellular and subcellular mechanisms of cardiac pacemaker oscillations. J Exp Biol. 1979; 81:205-15. DOI: 10.1242/jeb.81.1.205. View

11.

Morena H, Janse M, Fiolet J, Krieger W, Crijns H, Durrer D . Comparison of the effects of regional ischemia, hypoxia, hyperkalemia, and acidosis on intracellular and extracellular potentials and metabolism in the isolated porcine heart. Circ Res. 1980; 46(5):634-46. DOI: 10.1161/01.res.46.5.634. View

12.

Kaplinsky E, Ogawa S, Michelson E, DREIFUS L . Instantaneous and delayed ventricular arrhythmias after reperfusion of acutely ischemic myocardium: evidence for multiple mechanisms. Circulation. 1981; 63(2):333-40. DOI: 10.1161/01.cir.63.2.333. View

13.

Vassalle M, Mugelli A . An oscillatory current in sheep cardiac Purkinje fibers. Circ Res. 1981; 48(5):618-31. DOI: 10.1161/01.res.48.5.618. View

14.

Carbonin P, Di Gennaro M, Valle R, Weisz A . Inhibitory effect of anoxia on reperfusion- and digitalis-induced ventricular tachyarrhythmias. Am J Physiol. 1981; 240(5):H730-7. DOI: 10.1152/ajpheart.1981.240.5.H730. View

15.

Hoffman B, Rosen M . Cellular mechanisms for cardiac arrhythmias. Circ Res. 1981; 49(1):1-15. DOI: 10.1161/01.res.49.1.1. View

16.

Bourdillon P, Poole-Wilson P . Effects of ischaemia and reperfusion on calcium exchange and mechanical function in isolated rabbit myocardium. Cardiovasc Res. 1981; 15(3):121-30. DOI: 10.1093/cvr/15.3.121. View

17.

Bhattacharyya M, Vassalle M . The effect of local anaesthetics on strophanthidin toxicity in canine cardiac Purkinje fibres. J Physiol. 1981; 312:125-42. PMC: 1275545. DOI: 10.1113/jphysiol.1981.sp013620. View

18.

Horowitz J, Anavekar S, Morris P, GOBLE A, Doyle A, Louis W . Comparative trial of mexiletine and lignocaine in the treatment of early ventricular tachyarrhythmias after acute myocardial infarction. J Cardiovasc Pharmacol. 1981; 3(3):409-19. DOI: 10.1097/00005344-198105000-00001. View

19.

Clusin W, Bristow M, Karagueuzian H, KATZUNG B, Schroeder J . Do calcium-dependent ionic currents mediate ischemic ventricular fibrillation?. Am J Cardiol. 1982; 49(3):606-12. DOI: 10.1016/s0002-9149(82)80019-2. View

20.

Hohnloser S, Weirich J, ANTONI H . Effects of mexiletine on steady-state characteristics and recovery kinetics of V max and conduction velocity in guinea pig myocardium. J Cardiovasc Pharmacol. 1982; 4(2):232-9. DOI: 10.1097/00005344-198203000-00011. View