Use-dependent effects of lidocaine on conduction in canine myocardium: application of the modulated receptor hypothesis in vivo.

Abstract:

:Lidocaine is a commonly used antiarrhythmic drug that causes use-dependent blockade of sodium channels in vitro and reduces conduction velocity in vitro and in vivo. According to the modulated receptor hypothesis of antiarrhythmic drug action, lidocaine has a low affinity for rested sodium channels but a high affinity for open and inactivated channels. In the present experiments, we characterized use-dependent conduction slowing and recovery from slowing by lidocaine in anesthetized dogs. The His-to-ventricular conduction interval was used as the indicator of conduction velocity. We found that prolongation of conduction time was greater as the stimulation frequency was increased. Moreover, on abruptly changing the stimulation frequency, a new steady-state conduction time was approached in two to three depolarizations. On discontinuation of stimulation, the conduction time of progressively less premature extrastimuli shortened exponentially with a terminal phase time constant of 152 +/- 115 msec. These effects by lidocaine were enhanced during acidosis and enhancement was reversed by correction of the acidosis. It is concluded that the effects in vivo of lidocaine on conduction under several conditions of rate, rhythm, and pH are similar to its effects on the maximum upstroke velocity of the action potential in vitro. Although these experiments were not designed to validate the modulated receptor hypothesis, it appears that the modulated receptor hypothesis can predict the effects of lidocaine on conduction in vivo.

journal_name

Circulation

journal_title

Circulation

authors

Davis J,Matsubara T,Scheinman MM,Katzung B,Hondeghem LH

doi

10.1161/01.cir.74.1.205

subject

Has Abstract

pub_date

1986-07-01 00:00:00

pages

205-14

issue

1

eissn

0009-7322

issn

1524-4539

journal_volume

74

pub_type

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