Selective depression of conduction of premature action potentials in canine Purkinje fibres by class Ib antiarrhythmic drugs: comparison with Ia 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 Ia, Ib, 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 Ib 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Pallandi
R T
RT
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
Campbell
T J
TJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D046508:Culture Techniques; D003971:Diastole; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006329:Heart Conduction System / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D004338:Drug Combinations