Lidocaine does not affect myocardial electrical heterogeneity: implications for low proarrhythmic actions.
An area of unidirectional conduction block is one requirement for reentrant arrhythmias to occur. Functional block caused by dispersion of repolarization and refractoriness is the most probable mechanism of drug-induced unidirectional conduction block. We assessed the effects of lidocaine on spatial dispersion of myocardial repolarization and refractoriness in the intact porcine heart. Monophasic action potential duration at 90% repolarization, effective refractory period (ERP), and ventricular fibrillation cycle length (VFCL) were measured at two endocardial and one epicardial sites at baseline and during a treatment phase with D5W (n=11) or lidocaine 10 mg/kg/hour (n=12). Dispersion was calculated as the difference between the maximum and minimum values of the three recording sites. Lidocaine produced significant changes in ERP, VFCL, paced QRS duration, and intraventricular conduction time. It did not change basal levels of dispersion in repolarization and refractoriness. Lidocaine produced changes in myocardial electrophysiology that are uniform across the myocardium and thus did not change myocardial electrical heterogeneity. This may be a mechanism of the agent's lower proarrhythmic effects compared with other sodium channel blockers that increase myocardial electrical heterogeneity.
Sims
J J
JJ
University of Georgia College of Pharmacy, Augusta Veterans Affairs Medical Center, USA.
Winecoff
A P
AP
Ujhelyi
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D012033:Refractory Period, Psychological / Q000187:drug effects; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine