Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart

TY - JOUR

T1 - Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart

AU - Osadchiy, Oleg

PY - 2016/1/1

Y1 - 2016/1/1

N2 - OBJECTIVES: Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length.DESIGN: ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation.RESULTS: Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms).CONCLUSIONS: Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

AB - OBJECTIVES: Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length.DESIGN: ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation.RESULTS: Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms).CONCLUSIONS: Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

KW - Action Potentials

KW - Adaptation, Physiological

KW - Animals

KW - Anti-Arrhythmia Agents

KW - Arrhythmias, Cardiac

KW - Cardiac Pacing, Artificial

KW - Disease Models, Animal

KW - Electrocardiography

KW - Electrophysiologic Techniques, Cardiac

KW - Flecainide

KW - Guinea Pigs

KW - Heart Rate

KW - Heart Ventricles

KW - Male

KW - Sodium Channel Blockers

KW - Ventricular Function, Left

KW - Ventricular Function, Right

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.3109/14017431.2015.1099721

DO - 10.3109/14017431.2015.1099721

M3 - Journal article

C2 - 26402340

SN - 1401-7458

VL - 50

SP - 28

EP - 35

JO - Scandinavian Cardiovascular Journal, Supplement

JF - Scandinavian Cardiovascular Journal, Supplement

IS - 1

ER -