The frequency-dependent electrophysiological effects of lignocaine, sotalol, and their combination were studied in dog isolated cardiac Purkinje fibres, both at various constant rates of stimulation and following abrupt changes in pacing cycle length. The combined effect of 18 μM lignocaine and 30 μM sotalol selectively lengthened duration of premature action potentials evoked at a diastolic interval of 40 ms (from 172.2 ± 5.4 to 201.7 ± 4.9 ms, n = 6, P < 0.01) without significantly changing the durations of action potentials evoked at the basic cycle length of 500 ms (259.1 ± 7.7 vs 251.9 ± 3.9 ms, n = 11). The combination of lignocaine with sotalol, like lignocaine alone, displayed a use-dependent depression of V̇(max) and revealed a slow component for a recovery of V̇(max) (τ = 173.5 ± 16.0 ms, n = 5). The kinetics for restitution of action potential duration were also slowed by the combination of the two drugs (τ(f) = 173.6 ± 26.7, before, vs 268.5 ± 8.5 ms, after; n = 5, P < 0.01), while the maximum action potential duration attained in this relation was not increased as it was by sotalol alone. Lignocaine, therefore, appeared to inhibit the sotalol-induced lengthening of action potential duration at slow pacing rates and at long diastolic intervals. The combination of lignocaine with sotalol also completely abolished the occurrence of sotalol-induced early afterdepolarizations. Finally, sotalol alone moderately increased the range of premature action potential durations, while the combination of the two drugs significantly decreased this parameter. These findings indicate that the combination of lignocaine with sotalol may provide important, and unique, beneficial electrophysiological alterations that might be expected to provide enhanced anti-arrhythmic efficacy in patients.
|Number of pages||7|
|Journal||British Journal of Pharmacology|
|Publication status||Published - Jan 1 1990|
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