title: Procainamide and lidocaine produce dissimilar changes in ventricular repolarization and arrhythmogenicity in guinea-pig.
abstract: Procainamide is class Ia Na(+) channel blocker that may prolong ventricular repolarization secondary to inhibition of IK r , the rapid component of the delayed rectifier K(+) current. In contrast to selective IN a blockers such as lidocaine, procainamide was shown to produce arrhythmogenic effects in the clinical setting. This study examined whether pro-arrhythmic responses to procainamide may be accounted for by drug-induced repolarization abnormalities including impaired electrical restitution kinetics, spatial gradients in action potential duration (APD), and activation-to-repolarization coupling. In perfused guinea-pig hearts, procainamide was found to prolong the QT interval on ECG and left ventricular (LV) epicardial monophasic APD, increased the maximum slope of electrical restitution, enhanced transepicardial APD variability, and eliminated the inverse correlation between the local APD and activation time values determined at distinct epicardial recording sites prior to drug infusion. In contrast, lidocaine had no effect on electrical restitution, the degree of transepicardial repolarization heterogeneities, and activation-to-repolarization coupling. Spontaneous episodes of monomorphic ventricular tachycardia were observed in 57% of procainamide-treated heart preparations. No arrhythmia was induced by lidocaine. In summary, this study suggests that abnormal changes in repolarization may contribute to pro-arrhythmic effects of procainamide.
authors: Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen N 2200, Denmark; Department of Health Science and Technology, University of Aalborg, Fredrik Bajers Vej 7E, Aalborg 9220, Denmark.
authors: Oleg E
authors: OE
authors: Osadchii
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000633:toxicity*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D008012:Lidocaine / Q000494:pharmacology / Q000633:toxicity*; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology; D011342:Procainamide / Q000494:pharmacology / Q000633:toxicity*; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000503:physiopathology; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000889:Anti-Arrhythmia Agents; D061567:Voltage-Gated Sodium Channel Blockers; D008012:Lidocaine; D011342:Procainamide
keywords: lidocaine; pro-arrhythmia; procainamide; repolarization