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Antiarrhythmic drug effects on premature beats are partly determined by prior cardiac activation frequency in perfused guinea-pig heart.
Exp Physiol. 2020 May; 105(5):819-830.EP

Abstract

NEW FINDINGS

What is the central question of this study? Can antiarrhythmic drug effects on repolarization, conduction time and excitation wavelength in premature beats be determined by prior cardiac activation frequency? What is the main finding and its importance? In premature beats induced after a series of cardiac activations at a slow rate, antiarrhythmics prolong repolarization but evoke little or no conduction delay, thus increasing the excitation wavelength, which indicates an antiarrhythmic effect. Fast prior activation rate attenuates prolongation of repolarization, while amplifying the conduction delay induced by drugs, which translates into the reduced excitation wavelength, indicating proarrhythmia. These findings suggest that a sudden increase in heart rate can shape adverse pharmacological profiles in patients with ventricular ectopy.

ABSTRACT

Antiarrhythmic drugs used to treat atrial fibrillation can occasionally induce ventricular tachyarrhythmia, which is typically precipitated by a premature ectopic beat through a mechanism related, in part, to the shortening of the excitation wavelength (EW). The arrhythmia is likely to occur when a drug induces a reduction, rather than an increase, in the EW of ectopic beats. In this study, I examined whether the arrhythmic drug profile is shaped by the increased cardiac activation rate before ectopic excitation. Ventricular monophasic action potential durations, conduction times and EW values were assessed during programmed stimulations applied at long (S1 -S1 [basic drive cycle length] = 550 ms) and short (S1 -S1 = 200 ms) cycle lengths in perfused guinea-pig hearts. The premature activations were induced with extrastimulus application immediately upon termination of the refractory period. With dofetilide, a class III antiarrhythmic agent, a prolongation in action potential duration and the resulting increase in the EW obtained at S1 -S1 = 550 ms were significantly attenuated at S1 -S1 = 200 ms, in both the regular (S1) and the premature (S2) beats. With class I antiarrhythmic agents (quinidine, procainamide and flecainide), fast S1 -S1 pacing was found to attenuate the drug-induced increase in action potential duration, while amplifying drug-induced conduction slowing, in both S1 and S2 beats. As a result, although the EW was increased (quinidine and procainamide) or not changed (flecainide) at the long S1 -S1 intervals, it was invariably reduced by these agents at the short S1 -S1 intervals. These findings indicate that the increased heart rate before ectopic activation shapes the arrhythmic profiles by facilitating drug-induced EW reduction.

Authors+Show Affiliations

Department of Biomedical Sciences, University of Copenhagen, Copenhagen N, Denmark. Department of Health Science and Technology, University of Aalborg, Aalborg, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32175633

Citation

Osadchii, Oleg E.. "Antiarrhythmic Drug Effects On Premature Beats Are Partly Determined By Prior Cardiac Activation Frequency in Perfused Guinea-pig Heart." Experimental Physiology, vol. 105, no. 5, 2020, pp. 819-830.
Osadchii OE. Antiarrhythmic drug effects on premature beats are partly determined by prior cardiac activation frequency in perfused guinea-pig heart. Exp Physiol. 2020;105(5):819-830.
Osadchii, O. E. (2020). Antiarrhythmic drug effects on premature beats are partly determined by prior cardiac activation frequency in perfused guinea-pig heart. Experimental Physiology, 105(5), 819-830. https://doi.org/10.1113/EP088165
Osadchii OE. Antiarrhythmic Drug Effects On Premature Beats Are Partly Determined By Prior Cardiac Activation Frequency in Perfused Guinea-pig Heart. Exp Physiol. 2020;105(5):819-830. PubMed PMID: 32175633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiarrhythmic drug effects on premature beats are partly determined by prior cardiac activation frequency in perfused guinea-pig heart. A1 - Osadchii,Oleg E, Y1 - 2020/04/20/ PY - 2019/09/10/received PY - 2020/03/13/accepted PY - 2020/3/17/pubmed PY - 2020/3/17/medline PY - 2020/3/17/entrez KW - antiarrhythmic agents KW - excitation wavelength KW - premature beats SP - 819 EP - 830 JF - Experimental physiology JO - Exp. Physiol. VL - 105 IS - 5 N2 - NEW FINDINGS: What is the central question of this study? Can antiarrhythmic drug effects on repolarization, conduction time and excitation wavelength in premature beats be determined by prior cardiac activation frequency? What is the main finding and its importance? In premature beats induced after a series of cardiac activations at a slow rate, antiarrhythmics prolong repolarization but evoke little or no conduction delay, thus increasing the excitation wavelength, which indicates an antiarrhythmic effect. Fast prior activation rate attenuates prolongation of repolarization, while amplifying the conduction delay induced by drugs, which translates into the reduced excitation wavelength, indicating proarrhythmia. These findings suggest that a sudden increase in heart rate can shape adverse pharmacological profiles in patients with ventricular ectopy. ABSTRACT: Antiarrhythmic drugs used to treat atrial fibrillation can occasionally induce ventricular tachyarrhythmia, which is typically precipitated by a premature ectopic beat through a mechanism related, in part, to the shortening of the excitation wavelength (EW). The arrhythmia is likely to occur when a drug induces a reduction, rather than an increase, in the EW of ectopic beats. In this study, I examined whether the arrhythmic drug profile is shaped by the increased cardiac activation rate before ectopic excitation. Ventricular monophasic action potential durations, conduction times and EW values were assessed during programmed stimulations applied at long (S1 -S1 [basic drive cycle length] = 550 ms) and short (S1 -S1 = 200 ms) cycle lengths in perfused guinea-pig hearts. The premature activations were induced with extrastimulus application immediately upon termination of the refractory period. With dofetilide, a class III antiarrhythmic agent, a prolongation in action potential duration and the resulting increase in the EW obtained at S1 -S1 = 550 ms were significantly attenuated at S1 -S1 = 200 ms, in both the regular (S1) and the premature (S2) beats. With class I antiarrhythmic agents (quinidine, procainamide and flecainide), fast S1 -S1 pacing was found to attenuate the drug-induced increase in action potential duration, while amplifying drug-induced conduction slowing, in both S1 and S2 beats. As a result, although the EW was increased (quinidine and procainamide) or not changed (flecainide) at the long S1 -S1 intervals, it was invariably reduced by these agents at the short S1 -S1 intervals. These findings indicate that the increased heart rate before ectopic activation shapes the arrhythmic profiles by facilitating drug-induced EW reduction. SN - 1469-445X UR - https://www.unboundmedicine.com/medline/citation/32175633/Antiarrhythmic_drug_effects_on_premature_beats_are_partly_determined_by_prior_cardiac_activation_frequency_in_perfused_guinea-pig_heart L2 - https://doi.org/10.1113/EP088165 DB - PRIME DP - Unbound Medicine ER -
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