Frequency-dependent effect of quinidine, mexiletine, and their combination on postrepolarization refractoriness in vivo.

Journal of Cardiovascular Pharmacology
A Costard-JaeckleM R Franz

Abstract

Combination therapy with mexiletine and quinidine has been shown to enhance antiarrhythmic efficacy. To assess further the underlying electrophysiological mechanism, the effect of therapeutic concentrations of mexiletine and quinidine, and of their combination, on action potential duration (at the level of 90% repolarization, APD90), effective refractory (ERP), and the relationship between these two parameters (ERP-APD90) was determined in 21 in vivo canine hearts. The frequency dependence of these effects was assessed over a range of paced steady-state cycle lengths from 250-600 ms. A modified contact electrode technique allowed measurements of both APD90 and ERP simultaneously and at the same ventricular site. In the drug-free state, both APD90 and ERP shortened linearly with shorter cycle lengths, maintaining a constant relationship (ERP-APD90) difference = -9 +/- 2 ms) at all cycle lengths. Quinidine prolonged APD90 by a near constant amount of 11 +/- 1 ms over the entire range of cycle lengths, while mexiletine tended to shorten it. Both mexiletine and quinidine increased ERP and ERP-APD90 in a rate-dependent fashion, the effect increasing with shorter cycle lengths. When used in combination, mexiletine attenuated the leng...Continue Reading

Citations

Apr 18, 2007·Pflügers Archiv : European journal of physiology·Ian N SabirChristopher L-H Huang
Jun 1, 2005·Heart Rhythm : the Official Journal of the Heart Rhythm Society·José Jalife, Sandeep V Pandit
Oct 1, 1990·Journal of the American College of Cardiology·M R FranzM M Scheinman
Jan 1, 1993·Fundamental & Clinical Pharmacology·C Funck-Brentano
Oct 30, 1998·Pacing and Clinical Electrophysiology : PACE·Y MurakawaM Omata
Feb 1, 1996·Journal of Cardiovascular Electrophysiology·P T Sager, M Behboodikhah
Nov 2, 2014·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Michael R FranzSteven N Singh
Dec 7, 2010·Trends in Cardiovascular Medicine·Asli KalinIan N Sabir

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