Mechanisms of lidocaine actions on normal and abnormal rhythms in canine cardiac tissues in vivo and in vitro.
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.
Abete
P
P
Department of Physiology, State University of New York, Brooklyn 11203.
Ferrara
N
N
Rengo
F
F
Vassalle
M
M
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
D000889:Anti-Arrhythmia Agents; D013779:Tetrodotoxin; D013327:Strophanthidin; D008012:Lidocaine; D012964:Sodium; D011433:Propranolol; D002118:Calcium