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

Pallandi, Regan T.; Campbell, Terry

doi:10.1093/cvr/22.3.171

Cited by 14 publications

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“…This last finding is consistent with the work of Dresel (1984), and confirms a correlation between kinetics of drug action and effects on conduction velocity as shown previously for other agents (Man & Dresel, 1979;Pallandi & Campbell, 1988).…”

Section: Discussionsupporting

confidence: 93%

“…The preparation has been described elsewhere (Pallandi & Campbell, 1988). Cardiac Purkinje fibres (8-15mm long and 0.5-1.5mm in diameter) were obtained from a total of 6 adult mongrel dogs anaesthetized with sodium pentobarbitone.…”

Section: Dog Experimentsmentioning

confidence: 99%

“…premature action potential arising during repolarizaInterstimulus interval (ms) 600 500 400 300 tion of preceding potential; Pallandi & Campbell, 1988 …”

Section: Dog Experimentsmentioning

confidence: 99%

“…Encainide itself has been shown to have very slow kinetics (group 1C;Campbell, 1983b), so that at therapeutic concentrations, it tends to depress conduction of sinus beats and premature beats almost equally, thus prolonging intracardiac conduction times significantly (Pallandi & Campbell, 1988). MODE and ODE have been shown to produce rate-dependent depression of V,,.g (maximum rate of depolarization) of cardiac action potentials, as do all class 1 antiarrhythmic agents (Elharrar & Zipes, 1982), but these workers did not study the kinetics of onset and offset of these rate-dependent effects, nor their ability to depress P.. in the absence of prior stimulation ('resting block').…”

Section: Introductionmentioning

confidence: 99%

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Depression of maximum rate of depolarization of guinea‐pig ventricular action potentials by metabolites of encainide

Hemsworth

Campbell

1989

British J Pharmacology

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1 Standard microelectrode methods have been used to record action potentials from guinea-pig ventricular myocardium and dog Purkinje fibres, and to study the effects of the two major metabolites of encainide, 0-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (MODE). 2 In concentrations similar to those found in patients during chronic encainide therapy, neither ODE nor MODE produced significant depression of maximum rate of depolarization (P,..X) of action potentials in unstimulated tissue. Repetitive stimulation, however, was associated with depression of J, which increased with increasing driving rates (rate-dependent block, RDB). At the fastest rate studied (interstimulus interval = 300 ms) ODE 1 gM depressed P,., by 47.5 + 5.7%and MODE 1 gM, reduced Vx by 52.2 + 12%.3 The onset and offset kinetics of this rate-dependent block were very slow. Full development of RDB during a train required over 100 action potentials and the time constants of recovery of VP.,X from RDB were 86.4 + 37 s for ODE and 100.4 + 18 s for MODE. The amount of RDB and its rate of onset increased with drug concentration. The recovery time constants were independent of interstimulus interval or drug concentration. Both metabolites also produced rate-dependent depression of conduction velocity in canine Purkinje fibres, but no evidence of selective depression of conduction of interpolated premature potentials was seen. 4 Early afterdepolarizations occurred spontaneously in three preparations in the presence of MODE, 1 gM and one preparation in ODE, 1 gM. 5 It is concluded that these metabolites of encainide may play a role in producing both its antiarrhythmic and its proarrhythmic effects.

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Section: Discussionsupporting

confidence: 93%

Section: Dog Experimentsmentioning

confidence: 99%

“…premature action potential arising during repolarizaInterstimulus interval (ms) 600 500 400 300 tion of preceding potential; Pallandi & Campbell, 1988 …”

Section: Dog Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Depression of maximum rate of depolarization of guinea‐pig ventricular action potentials by metabolites of encainide

Hemsworth

Campbell

1989

British J Pharmacology

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“…the blocking action on the maximum rate of rise of the action potential (Campbell, 1983;Pallandi & Campbell, 1988;Hattori et al, 1986;.…”

mentioning

confidence: 99%

Different time courses of the blockade of sodium current by lignocaine and SUN 1165 in single myocytes isolated from guinea‐pig atrium

Inomata

Ishihara

Akaike

1989

British J Pharmacology

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The time course of the blockade of sodium currents (INa) by the antiarrhythmic agents, lignocaine and SUN 1165, was studied in single myocytes isolated enzymatically from guinea‐pig atrium, by a new concentration‐jump termed as a ‘concentration‐clamp’ technique. This technique combines an intracellular perfusion and a rapid exchange of external solution surrounding the voltage‐clamped myocyte within 2 ms. Lignocaine (3.7 × 10−5 m to 3.7 × 10−4 M) inhibited the peak amplitude of INa in a concentration‐dependent fashion. It took 2 to 5 s to reach apparent steady‐state inhibition at the concentrations used. Complete recovery from the inhibition also took 2 to 5 s after washing out the agent. In contrast, the inhibitory effect of SUN 1165 (1 × 10−5 M) on the peak INa gradually progressed and reached a steady‐state level about 2 min after the start of drug‐application. The recovery required more than 10 min after washing out of the agent. In cardiomyocytes treated with scorpion toxin (5 μg ml−1), the inactivation of INa was greatly inhibited, resulting in the relatively persistent Na inward current (persistent INa) during the depolarizing pulse. Lignocaine (1.1 × 10−4 M) applied during the depolarizing pulse, reduced in a single‐exponential fashion the amplitude of the persistent INa in milliseconds. On the other hand, lignocaine applied several tens of milliseconds before the depolarizing pulse induced only a small reduction of the peak amplitude of the first persistent INa. When SUN 1165 (1 × 10−5 M) was applied during the depolarizing pulse, there was only a small instantaneous reduction of the amplitude of the persistent INa, although it did inhibit time‐dependently, the peak INa. Both agents accelerated the decay phase of the persistent INa in a time‐dependent manner. These results suggest that lignocaine and SUN 1165 may preferentially interact with the open‐state of the sodium channel rather than with the rested one, although SUN 1165 does so much more slowly.

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Subclassification of Class I antiarrhythmic drugs: Enhanced relevance after CAST

Campbell

1992

Cardiovasc Drug Ther

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Class I antiarrhythmic drugs are traditionally divided into three subclasses--Ia, Ib, and Ic--on the grounds of differences in kinetics of interaction with the sodium channel and different effects on the duration of the action potential. The CAST study has highlighted our growing awareness of the proarrhythmic potential of this group of agents, particularly the Class Ic subgroup. Class I drugs can cause arrhythmias either by slowing conduction to critical levels, thus enhancing the possibility of reentrant arrhythmias, or in some cases by prolonging action potential duration, leading to early afterdepolarizations, which probably underlie triggered automaticity. Evidence is presented that the Class Ic compounds may be inherently more proarrhythmic than the Ib compounds, because of their lesser ability to depress ischemic myocardium selectively. Arguments are advanced for the continued use of a slightly modified subclassification of Class I antiarrhythmic drugs.

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

Cited by 14 publications

References 0 publications

Depression of maximum rate of depolarization of guinea‐pig ventricular action potentials by metabolites of encainide

Depression of maximum rate of depolarization of guinea‐pig ventricular action potentials by metabolites of encainide

Different time courses of the blockade of sodium current by lignocaine and SUN 1165 in single myocytes isolated from guinea‐pig atrium

Subclassification of Class I antiarrhythmic drugs: Enhanced relevance after CAST

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