Electrophysiological Actions of Lidocaine on Canine Ventricular Muscle and Purkinje Fibers

Davis, Larry D.; Temte, John V.

doi:10.1161/01.res.24.5.639

Cited by 157 publications

(52 citation statements)

References 55 publications

(62 reference statements)

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“…The highest concentration of lignocaine studied significantly shortened the human ventricular action potential duration at 50 and 90% repolarization levels, the effect being similar in both [K + ]. These results are in agreement with those obtained in both canine and rabbit ventricular muscle (Davis & Temte, 1969;Singh & Vaughan Williams, 1971 Davis & Temte (1969). This prolongation of ARP, independent of a lengthening in APD, may be explained by the ability of lignocaine to prolong the reactivation kinetics of the rapid inward sodium current (Chen et al, 1975).…”

Section: Discussionsupporting

confidence: 89%

COMPARATIVE ELECTROPHYSIOLOGICAL EFFECTS OF Org 6001, A NEW ORALLY ACTIVE ANTIDYSRHYTHMIC AGENT, AND LIGNOCAINE ON HUMAN VENTRICULAR MUSCLE

Kane

1980

British J Pharmacology

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The electrophysiological effects of Org 6001, a new orally active antidysrhythmic agent, have been compared with those of lignocaine on the human ventricular action potential in vitro. 2 Org 6001 (4 to 16 mg/l) greatly reduced the maximum rate of depolarization (MRD) of the human ventricular action potential but had no effect on resting membrane potential or action potential amplitude. 3 The action potential duration at the 50% repolarization level, but not at the 90% repolarization level, was significantly reduced by Org 6001. The absolute refractory period was unchanged. 4 Lignocaine, at a concentration (4 mg/l) within the therapeutic range, had no significant effect on any measured parameter, either in muscle exposed to a normal (4.0 mM) or high (5.4 mM) extracellular potassium concentration ([K+]j. 5 Higher concentrations of lignocaine (8 to 16 mg/i) did, however, reduce MRD at both [K+].without changing resting membrane potential or action potential amplitude. The action potential duration was decreased slightly by these higher concentrations of lignocaine whilst the absolute refractory period was lengthened. 6 Org 6001 was found to be more potent than lignocaine in reducing MRD but, unlike lignocaine, the absolute refractory period was not prolonged. These compounds, therefore, differed in their electrophysiological effects on human ventricular muscle although both are characterized as being class I antidysrhythmic drugs.

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Section: Discussionsupporting

confidence: 89%

COMPARATIVE ELECTROPHYSIOLOGICAL EFFECTS OF Org 6001, A NEW ORALLY ACTIVE ANTIDYSRHYTHMIC AGENT, AND LIGNOCAINE ON HUMAN VENTRICULAR MUSCLE

Kane

1980

British J Pharmacology

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“…However, the electrophysiological effect of lignocaine on isolated canine Purkinje fibres and ventricular muscle have been studied in detail (Davis & Temte, 1969;Bigger & Mandel, 1970a, b). Its effects have been compared with those of propranolol (Davis & Temte, 1968).…”

Section: Introductionmentioning

confidence: 99%

Effects of lignocaine and propranolol on experimental cardiac arrhythmias

Allen

Shanks

Zaidi

1971

British J Pharmacology

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Summary1. The effects of intravenous injection of lignocaine and propranolol were studied in dogs. 2. Ventricular ectopic beats produced by intravenous injection of adrenaline in anaesthetized dogs respired with halothane were abolished in four out of six dogs by lignocaine. Propranolol was effective in all three dogs tested. 3. Intravenous infusion of lignocaine at (0-2 and 10 mg/kg)/min to total doses of 3-0+110 and 2-2+0±5 mg/kg, respectively, abolished the ventricular tachycardia produced in anaesthetized dogs by ouabain. A similar effect was produced by infusion of propranolol at (0-2 mg/kg)/min to a total dose of 1P9+0±4 mg/kg. Intravenous injection of single doses of lignocaine (4-0-8-0 mg/kg) also abolished the arrhythmia. 4. The frequency of the ventricular ectopic beats occurring in conscious dogs 20-44 h after ligation of the anterior descending branch of the left coronary artery was reduced, with an increase in the number of sinus beats, after intravenous injection of lignocaine (8-0 mg/kg). Larger doses produced excitement. Propranolol (4 0 mg/kg) had a greater effect than the same dose of lignocaine but after 8-0 mg/kg, three of the four dogs died. 5. Propranolol was more effective than lignocaine in abolishing the three different types of arrhythmia. 6. Dose-response curves showed that lignocaine was more active in abolishing the ouabain induced arrhythmia than the halothane-adrenaline arrhythmia and was least active on the arrhythmia caused by ligation of the coronary artery.

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“…Previous studies had shown that lidocaine at therapeutic concentrations suppresses normal automaticity and delayed afterdepolarizations. 22,23 The effects of the drug matrix on mechanisms for normal and abnormal impulse initiation have been studied extensively, as have its effects on conduction.9-12,18,23,26 However, knowledge of its actions on cell coupling, on passive membrane properties, and on threshold for excitability are incomplete. Needless to say, such information would be valuable in furthering our understanding of the actions of the drugs in the matrix.…”

Section: Discussionmentioning

confidence: 99%

“…The Purkinje fibers were impaled with 3 M KCIfilled glass microelectrodes having tip resistances of [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Mfl. Attempts were made to impale the site of earliest impulse initiation, at which the slope of phase 4 and phase 0 merged smoothly in the typical configuration of a pacemaker fiber.…”

Section: Methodsmentioning

confidence: 99%

Premature escape beats induced by overdrive pacing in canine Purkinje fibers. Evidence for the role of normal automaticity as an underlying cellular mechanism.

Viamonte

Rosen

1990

Circulation

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Premature escape beats induced in conscious dogs with chronic complete atrioventricular block have been defined as escape beats occurring on cessation of overdrive pacing and having a coupling interval to the last paced beat shorter than the coupling interval between the premature escape beat and the second postpacing beat. Triggered activity has been proposed as the primary underlying mechanism. We used standard microelectrode techniques to study the effects of overdrive pacing on normal automatic canine Purkinje fibers to determine if premature escape beats could be induced and if so, to define the underlying cellular mechanism(s). For this purpose, we overdrive-paced Purkinje fibers for 10 and 50 seconds and for 10 and 50 beats at a pacing cycle length (PCL) of 1,000-200 msec. In addition, to help distinguish among major arrhythmogenic mechanisms, we used a matrix of drugs consisting of propranolol, nadolol, lidocaine, ethmozin, and doxorubicin. Fifty-second stimulation trains induced "classic"1 overdrive suppression of the first three postpacing impulses, whereas 10-second overdrive pacing induced significant overdrive suppression only at a PCL of 200 msec. With 50-beat overdrive pacing and a PCL of 1,000-600 msec, there was overdrive suppression of postpacing impulses, whereas reduced overdrive suppression was observed at a PCL of 400-200 msec. Ten-beat stimulation trains induced a "flat response" of postpacing impulses. Ten-and 50-beat overdrive pacing provoked premature escape beats in 66% of the fibers, with the higher incidence at a PCL of 200 msec for 50-beat stimulation trains. No shortening of the coupling interval of premature escape beats was observed at faster pacing rates. Only lidocaine (which suppresses normal automaticity) abolished premature escape beats. We conclude that normal automaticity is the most likely mechanism underlying premature escape beats in Purkinje fibers with high levels of membrane potential. (Circulation 1990;82:234-243) O verdrive suppression, the quiescent period after rapid stimulation of a pacemaker cell, "qk.owl was well characterized during the 1960s and 1970s. In vivo and in vitro experiments demonstrated the duration of suppression to depend on the rate and duration of the period of overdrive pacing.1-' This property of automatic rhythms has been used to distinguish them from other mechanisms underlying normal and abnormal cardiac rhythms.Recently, Gorgels et al6,7 studied the effects of ventricular pacing in conscious dogs one week after From the

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Electrophysiological Actions of Lidocaine on Canine Ventricular Muscle and Purkinje Fibers

Cited by 157 publications

References 55 publications

COMPARATIVE ELECTROPHYSIOLOGICAL EFFECTS OF Org 6001, A NEW ORALLY ACTIVE ANTIDYSRHYTHMIC AGENT, AND LIGNOCAINE ON HUMAN VENTRICULAR MUSCLE

COMPARATIVE ELECTROPHYSIOLOGICAL EFFECTS OF Org 6001, A NEW ORALLY ACTIVE ANTIDYSRHYTHMIC AGENT, AND LIGNOCAINE ON HUMAN VENTRICULAR MUSCLE

Effects of lignocaine and propranolol on experimental cardiac arrhythmias

Premature escape beats induced by overdrive pacing in canine Purkinje fibers. Evidence for the role of normal automaticity as an underlying cellular mechanism.

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