RT Journal Article SR Electronic T1 Attenuation of proarrhythmias related to delayed repolarization by low-dose lidocaine in the anesthetized rabbit. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1076 OP 1080 VO 267 IS 3 A1 L Carlsson A1 L Drews A1 G Duker A1 G Schiller-Linhardt YR 1993 UL http://jpet.aspetjournals.org/content/267/3/1076.abstract AB 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)