Reassessment of the electrophysiological effects of the antiarrhythmic agent quinidine in canine Purkinje fibers

Wang, Ching M.; Parker, Charles H.

doi:10.1016/0024-3205(80)90007-7

Cited by 11 publications

(8 citation statements)

References 22 publications

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“…They found 1 (IM to be without effect, but 3 jtM prolonged APD90 and depressed W mMX . On the othe hand, Wang and Parker (1980) found that V^ depression and APD90 shortening were the most prominent effects of quinidine up to concentrations of 20 HM without significant APD 95 changes when fibers were driven at a cycle length of 800 msec in (1981), but the trend toward shortening at higher concentrations reported by Wang and Parker (1980) was found in our data. As discussed below, this change may reflect blockade of the window current.…”

Section: Discussioncontrasting

confidence: 52%

“…However, action potential prolongation itself may be antiarrhythmic by decreasing dispersion of repolarization, i.e., by producing disproportionately greater increases in short action potentials. Whereas data in this study were collected from mid-false tendon, others have reported that quinidine exerts disproportionately greater effects on action potential in 'post-gate* fibers, thereby reducing dispersion of repolarization (Wang and Parker, 1980). Hence, low concentrations of quinidine might be antiarrhythmic by such an effect on action potential duration without depressing V^.…”

Section: Discussionmentioning

confidence: 86%

“…In fact, concentrations over 30 HM frequently produce irreversible depolarization and inexdtability (Weld et al, 1980). However, with few exceptions (Wang and Parker, 1980;Mirro et al, 1981), the effects of much lower concentrations have not been well studied. We therefore undertook an evaluation of the effects of changes in [K + ]o and cycle length on the electrophysiological actions of a range of quinidine concentrations in canine Purkinje fibers.…”

mentioning

confidence: 99%

“…(Wang and Parker, 1980). Colatsky (1982) attributed action potential prolongation by quinidine in rabbit Purkinje fibers to blockade of the delayed potassium rectifier (i x ).…”

mentioning

confidence: 99%

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Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length.

Roden¹,

Hoffman²

1985

Circulation Research

320

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SUMMARY. Marked QT prolongation with induction of polymorphous ventricular tachycardia ('Torsades de Pointes') is a well-described phenomenon during quinidine therapy, frequently occurring at low plasma quinidine concentrations, low serum potassium, and slow heart rates. We have therefore assessed the dose-electrophysiological effects of quinidine as a function of extracellular potassium and cycle length in canine Purkinje fibers, using standard microelectrode techniques. Quinidine (1 MM) prolonged action potential at 90% repolarization, while leaving phase zero upstroke slope (Vm«) unchanged at a cycle length 300-8000 msec; at 10 MM, V,,,,,, depression became evident. Increases in the action potential at 90% repolarization were most marked at long cycle lengths and low extracellular potassium (in contrast to V^ depression) and were partially reversed by tetrodotoxin (1 M M )-The relationship between log of cycle length and action potential at 90% repolarization was linear (for cycle length 300-8000 msec) in the absence of quinidine. Quinidine increased the slope of this relationship in a concentration-related fashion, whereas increasing extracellular potassium shifted the curve rightward (without changing slope), regardless of the presence or absence of quinidine. Action potentials were also measured following pauses of 5-60 seconds. In the absence of quinidine, the action potential depolarization returned to its baseline value in a monoexponential fashion (time constant 36.0 ± 4.9 sec, mean ± SE, n = 10). In the presence of 1 JIM quinidine, this return was better fit as a biexponential process (time constants 4.2 ± 1 . 2 and 40.7 ± 6.2 seconds, n = 14). At slow stimulation rates (cycle length greater than 4000 msec) in low extracellular potassium (2.7 mM), quinidine produced early afterdepolarizations in 7/14 (50%) of fibers at 1 MM and 14/18 (78%) at 10 MM. Early afterdepolarizations were eliminated by increasing stimulation rates, raising the extracellular potassium concentration to 5 mM, or adding tetrodotoxin. These data suggest that prolongation by quinidine of action potentials at 90% repolarization is multifactorial, with both a 'tonic' prolonging effect and a prominent frequency-dependent action potential shortening effect. At long cycle lengths and low extracellular potassium, low quinidine concentrations consistently produced early afterdepolarizations. The parallels between this form of triggered activity and clinical arrhythmias induced by quinidine suggest that early afterdepolarizations may play a role in quinidine-induced Torsades de Pointes. (Circ Res 56: 857-867, 1985)

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

“…(Wang and Parker, 1980). Colatsky (1982) attributed action potential prolongation by quinidine in rabbit Purkinje fibers to blockade of the delayed potassium rectifier (i x ).…”

mentioning

confidence: 99%

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Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length.

Roden¹,

Hoffman²

1985

Circulation Research

320

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“…According to its kinetic properties, dridocainide is closest to the subgroup of I.A drugs, which have offset time constants between 2.2 and 4.7 s, and onset rate constants between 0.05 and 0.11 per action potential (Courtney 1980;Grant et al 1982;Campbell 1983b, c). In spite of these kinetic similarities, neither can dridocainide be classified as a I.A agent like quinidine, disopyramide or procainamide--drugs which have been shown to shorten APDs0 but prolong APDgo in canine Purkinje fibres (Rosen et al 1973;Kus and Sasyniuk 1978;Wang and Parker 1980).…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological effects of dridocainide on isolated canine, guinea-pig and human cardiac tissues

Pankucsi

Hegedüs

Kovács

et al. 1995

Naunyn-Schmiedeberg's Arch Pharmacol

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The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel class I antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibres and papillary muscle preparations obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6-2 mumol/l) decreased the maximum velocity of action potential upstroke (Vmax) in a frequency-dependent manner, although marked differences were observed in its effects in Purkinje fibre and ventricular muscle preparations. In canine Purkinje fibres, action potential duration measured at 50% and 90% of repolarization was decreased, while action potential duration measured at 10% of repolarization was increased by dridocainide. In addition, the plateau of the action potential was depressed by the drug. These changes in action potential configuration were not observed in guinea pig or human papillary muscles. The offset kinetics of the dridocainide-induced Vmax block were different in Purkinje fibres and in ventricular muscle: the slow time constant of recovery of Vmax was estimated to be 2.5 s in dog Purkinje fibre and 5-6 s in human and guinea-pig papillary muscle. In guinea-pig papillary muscle, the rate of onset of the Vmax block was 0.15 and 0.2 per action potential in the presence of 0.6 and 2 mumol/l dridocainide, respectively. Dridocainide also decreased the force of contraction in this preparation. On the basis of the present results, dridocainide appears to possess mixed class I.C and I.A properties, with I.C predominance in human and guinea-pig ventricular muscle. Present results also indicate that results of conventional classification of class I drugs may depend on the parameters chosen, as well as on the preparation selected.

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Wirkungsspektren von Antiarrhythmika und Betarezeptorenblockern

Tritthart¹

1983

Herzrhythmusstörungen

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Reassessment of the electrophysiological effects of the antiarrhythmic agent quinidine in canine Purkinje fibers

Cited by 11 publications

References 22 publications

Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length.

Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length.

Electrophysiological effects of dridocainide on isolated canine, guinea-pig and human cardiac tissues

Wirkungsspektren von Antiarrhythmika und Betarezeptorenblockern

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