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  • Title: Attenuation of proarrhythmias related to delayed repolarization by low-dose lidocaine in the anesthetized rabbit.
    Author: Carlsson L, Drews L, Duker G, Schiller-Linhardt G.
    Journal: J Pharmacol Exp Ther; 1993 Dec; 267(3):1076-80. PubMed ID: 8263767.
    Abstract:
    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)
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