Effect of antiarrhythmic drugs on the premature action potential duration in canine cardiac Purkinje fibers

A. Varro, V. Elharrar, B. Surawicz

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We studied the effect of six class I antiarrhythmic drugs, i.e., quinidine (5 μg/ml), disopyramide (10 μg/ml), procainamide (30 μg/ml), flecainide (4 μg/ml), lidocaine (4 μg/ml) and mexiletine (4 μg/ml), on the durations of the basic action potential (APD(b)) at a cycle length of 500 ms and on the premature APD (APD(t)) elicited at progressively increasing diastolic intervals (DI) in canine Purkinje fibers. The difference between APD(t) elicited at diastolic intervals of 100 msec and the earliest APD(t) elicited at the onset of effective refractory period was defined as the range of APD(t). In control this range was 98 ± 1.8 ms (n = 59). Disopyramide and procainamide did not change the range significantly but the other four drugs decreased it significantly (P < .01) as follows: quinidine by 50.2%, lidocaine by 60.2%, mexiletine by 61.6% and flecainide by 61.4%. The following four factors contributed to this decrease in range of APD(t): shorter duration of APD(b), increased effective refractory period/APD ratio, slower kinetics of APD restitution, and shift of normalized restitution curve toward longer APD(t) values. The magnitude of the contribution made by each of the above factors varied with different drugs. The greatest contributing factor for quinidine was an increased effective refractory period/APD ratio, for lidocaine a slower restitution and for flecainide and mexiletine the shift of the restitution curve. We concluded that antiarrhythmic drugs belonging to the same class have different effects on the range of premature APD and that these effects cannot be predicted from the effect of the drug on APD(b) alone.

Original languageEnglish
Pages (from-to)304-311
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume233
Issue number2
Publication statusPublished - Jan 1 1985

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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