Postrepolarization Refractoriness Versus Conduction Slowing Caused by Class I Antiarrhythmic Drugs

Abstract

Background-Conduction block may be both antiarrhythmic and proarrhythmic. Drug-induced postrepolarization refractoriness (PRR) may prevent premature excitation and tachyarrhythmia induction. The effects of propafenone and procainamide on these parameters, and their antiarrhythmic or proarrhythmic consequences, were investigated. Methods and Results-In 11 isolated Langendorff-perfused rabbit hearts, monophasic action potentials (MAPs) were recorded simultaneously from six to seven different right and left ventricular sites, along with a volume-conducted ECG. All recordings were used to discern ventricular tachycardia (VT) or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5) or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of procainamide (20 mol/L) or propafenone (1 mol/L) to the perfusate. MAPs were analyzed for action potential duration at 90% repolarization (APD 90 ), conduction times (CT) between the pacing site and the other MAPs, and PRR (effective refractory periodϪAPD 90 ϭPRR) and related to the induction of VT or VF. During steady-state pacing, procainamide and propafenone prolonged APD 90 by 12% and 14%, respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing, whereas propafenone slowed mean CT by up to 400% (PϽ0.001 versus baseline and procainamide). Wavelength was not changed significantly by procainamide but was shortened fourfold by propafenone at S5. Both drugs produced PRR, which was associated with a 70% decrease in VF inducibility with procainamide and elimination of VF with propafenone. Despite this protection from VF, monomorphic VT was induced with propafenone in 57% of burst stimulations. Conclusions-Drug-induced PRR protects against VF induction. Propafenone promotes slow monomorphic VT, probably by use-dependent conduction slowing and wavelength shortening. (Circulation. 1998;97:2567-2574.)

Electrophysiological, Anatomical and Histological Remodeling of the Heart to AV Block Enhances Susceptibility to Arrhythmogenic Effects of QT-Prolonging Drugs

“…More importantly, the prolongation of the MAP duration was more marked than that of the ERP in the chronic phase, particularly at a slower heart rate, indicating the prolongation of the electrically vulnerable period of the ventricle. These local electrophysiological changes indicate increase in the risk of aberrant excitation, which may provide a "substrate" for re-entry arrhythmias, leading to the onset of TdP (14,15).…”

Effects of Disopyramide and Mexiletine on the Terminal Repolarization Process of the In Situ Heart Assessed Using the Halothane-Anesthetized In Vivo Canine Model.

“…Moreover, a MAP recording/pacing combination catheter was used to Circulation Journal Vol.66, September 2002 simultaneously measure both MAP and effective refractory period (ERP) at the same site to assess the drug effects on the terminal repolarization period (phase 3) of the action potential. [3][4][5][6][7][8][9][10][11][14][15][16][17] …”

“…[3][4][5][6][7][8][9][10][11] Class I drugs are known to affect the QT interval, 12,13 but information regarding the effects of class I antiarrhythmic drugs in this type of model is still limited. [14][15][16][17] In this study, we simultaneously assessed the in vivo electrophysiological and cardiohemodynamic effects of typical class I antiarrhythmic drugs, disopyramide and mexiletine, using the halothane-anesthetized canine model. To better analyze the electrophysiological effects on the depolarization/repolarization process, we recorded His bundle electrograms and monophasic action potentials (MAPs), respectively, in addition to the standard lead II surface ECG.…”

“…The terminal repolarization period (TRP) of the action potential was calculated as TRP = MAP90(CL400) -ERP, which would reflect the extent of the electrical vulnerability of the heart. [3][4][5][6][7][8][9][10][11][14][15][16][17]19 …”

Influence of age on inducibility and cholinergic modulation of arrhythmia in isolated rat right atria

“…Additionally, in the present study, seeking a more quantitative methodological approach, we related SS to arrhythmia inducibility. By using a similar approach, Kirchhof et al (1998Kirchhof et al ( , 2003 showed the antiarrhythmic and proarrhythmic effects on ventricular fibrillation of amiodarone, procainamide and propafenone. Therefore, the use of SS seems to be suitable for the evaluation of arrhythmia inducibility in diverse experimental conditions.…”