Selective depression of conduction of premature action potentials in canine Purkinje fibres by class lb antiarrhythmic drugs: comparison with la and Ic drugs.

Microelectrodes were used to record action potentials and to estimate their conduction velocity in canine Purkinje fibres 8-15 mm long mounted in a tissue bath. The effects of varying stimulation rates and protocols were studied in the presence of nine different class I antiarrhythmic drugs at each of two concentrations (high and low therapeutic range). In all cases, as stimulation rate increased (range of cycle lengths 1000 ms to 200 ms), conduction velocity in the presence of a drug fell progressively below that in control solution at the same rate. No major differences in rate dependent behaviour at steady state were observed between the subclasses la, lb, and Ic. Differences were apparent, however, in the rate at which conduction velocity fell after a sudden decrease in cycle length. This was studied using two protocols. In the first of these, the conduction velocity was recorded of each action potential of a 20 beat train induced after a long rest period. In the presence of class lb drugs (lignocaine, tocainide, and mexiletine) there was a rapid decline within 2-3 beats to a new equilibrium level of conduction velocity. Class Ia drugs (quinidine, disopyramide, and procainamide) required 12-16 beats to achieve equilibrium, and class Ic agents (flecainide, encainide, and lorcainide) produced slow falls in conduction velocity that did not reach equilibrium within the 20 beat trains. The second protocol involved interpolation of increasingly premature extrastimuli. Class Ib drugs progressively slowed conduction of premature beats as the diastolic interval was reduced below 300-400 ms. Class Ia and Ic agents had no significant effect except when the diastolic interval was less than zero (that is, a premature beat arising during repolarisation of normal drive action potential). A combination of lignocaine (Ib) with quinidine (Ia) and flecainide (Ic) behaved similarly to class Ib drugs alone. It is concluded that class Ib antiarrhythmic drugs, with fast kinetics of interaction with sodium channels, may selectively depress early extrasystoles with little effect on normal beats. [ABSTRACT FROM PUBLISHER]