title: Mechanisms of lidocaine actions on normal and abnormal rhythms in canine cardiac tissues in vivo and in vitro.
abstract: 1. The actions of lidocaine on cardiac pacemaker rhythms were studied in anaesthetized dogs and in Purkinje fibres from hearts of the same animals. 2. In vivo, lidocaine (1 mg/kg, intravenously) slowed the sino-atrial (SA) node rhythm (-5.0%), and (during vagal stimulation) prolonged ventricular standstill by +25.1% and slowed the idioventricular rhythm (-16.7%). A higher dose (4 mg/kg) had more pronounced effects. 3. Propranolol also slowed sinus (-26.2%) and idioventricular (-27.2%) rhythms, and prolonged ventricular standstill (+36.8%). In the presence of propranolol, the effects of lidocaine on idioventricular rhythm were exaggerated. 4. In Purkinje fibres driven in vitro, lidocaine (10 mumol/L) decreased contractile force (-47.9%) and (during the interruption of drive) prolonged the suppression of (+53.2%) and slowed the escape rhythm (-67.0%). 5. In the presence of lidocaine the threshold potential was shifted to less negative values and diastolic depolarization slope was decreased (-23.6%). 6. Lidocaine slowed spontaneously active Purkinje fibres, abolished early afterdepolarizations in low [K]o and slow responses in high [K]o (by shifting the threshold to less negative values), and antagonized strophanthidin arrhythmias. 7. TTX reduced the hyperpolarization by lidocaine in low [K]o and vice versa. 8. We conclude that lidocaine enhances vagally-induced ventricular standstill by depressing the idioventricular rhythm far more than the sinus rhythm, an action enhanced by beta-blockade. Furthermore, lidocaine depresses normal and different types of abnormal automaticity through direct and indirect effects of the blockade of the fast sodium channel.
authors.affiliation: Department of Physiology, State University of New York, Brooklyn 11203.
authors.forename: P
authors.initials: P
authors.lastname: Abete
authors.forename: N
authors.initials: N
authors.lastname: Ferrara
authors.forename: F
authors.initials: F
authors.lastname: Rengo
authors.forename: M
authors.initials: M
authors.lastname: Vassalle
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000633:toxicity; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013327:Strophanthidin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D013779:Tetrodotoxin; D013327:Strophanthidin; D008012:Lidocaine; D012964:Sodium; D011433:Propranolol; D002118:Calcium