Attenuation of proarrhythmias related to delayed repolarization by low-dose lidocaine in the anesthetized rabbit.
Polymorphous ventricular tachyarrhythmias (torsades de pointes) were induced in seven of eight (88%) anesthetized rabbits receiving the class III antiarrhythmic agent almokalant (25 nmol/kg/min i.v.). The tachyarrhythmia was preceded by a significant lengthening of the QT interval from 118 +/- 7.2 to 148 +/- 9.0 msec, P < .01. Two separate groups of eight rabbits in each were given lidocaine (4.3 mumol/kg + 12.8 mumol/kg/hr or 12.8 mumol/kg + 38.4 mumol/kg/hr), before almokalant was administered. In comparison with the vehicle-pretreated rabbits, lidocaine treatment caused a dose-dependent attenuation in the incidence of torsades de pointes. Hence, the incidence was reduced to four of eight (50%, P = .1538 vs. the vehicle-treated group) rabbits and to none of eight (0%; P = .0007) rabbits in the groups treated with the "low" and the "high" dose of lidocaine, respectively. This attenuation was observed despite a significant prolongation of the QT interval by almokalant (from 128 +/- 7.6 to 175 +/- 15.9 msec, P < .01, and from 116 +/- 8.4 to 159 +/- 10.3 msec, P < .001, respectively). Acute injection of lidocaine (12.8 mumol/kg, n = 4) during recurrent episodes of torsades de pointes in vehicle-treated rabbits caused an abrupt restoration of sinus rhythm without influencing the almokalant-induced prolongation of the QT interval. It is concluded that lidocaine may inhibit the initiation of and suppress rhythm abnormalities related to delayed repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Carlsson
L
L
Astra Hässle AB, Preclinical Research and Development, Cardiovascular Pharmacology, Mölndal, Sweden.
Drews
L
L
Duker
G
G
Schiller-Linhardt
G
G
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008012:Lidocaine / Q000097:blood / Q000494:pharmacology*; D008297:Male; D011412:Propanolamines / Q000097:blood / Q000633:toxicity; D011817:Rabbits; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D008012:Lidocaine; C074334:almokalant