Attenuation of proarrhythmias related to delayed repolarization by low-dose lidocaine in the anesthetized rabbit
Carlsson, L.; Drews, L.; Duker, G.; Schiller-Linhardt, G.
Journal of Pharmacology and Experimental Therapeutics 267(3): 1076-1080
1993
ISSN/ISBN: 0022-3565 PMID: 8263767 Document Number: 418997
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 lt .01. Two separate groups of eight rabbits in each were given lidocaine (4.3 mu-mol/kg + 12.8 mu-mol/kg/hr or 12.8 mu-mol/kg + 38.4 mu-mol/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 = .1 538 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 lt .01, and from 116 +- 8.4 to 159 +- 10.3 msec, P lt .001, respectively). Acute injection of lidocaine (12.8 mu-mol/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. Based on these in vivo observations it is speculated that a depolarizing sodium current may play a decisive role in the initiation of torsades de pointes and/or that sodium channel blockade may prevent propagation of early after depolarizations from its site of origin to the ventricular muscle cell.