Frequency-dependent cardiac electrophysiologic effects of tedisamil

Comparison with quinidine and sotalol

M. Nemeth, A. Varró, L. Virág, O. Hála, D. Thormahlen, J. Papp

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Tedisamil is a potent bradycardic/antiischemic drug known to lengthen cardiac repolarization by blocking various potassium channels. Recent in vivo experiments revealed that it is an antiarrhythmic agent. It was therefore of interest to compare the cellular electrophysiologic effects of tedisamil with those of quinidine and sotalol in isolated cardiac preparations. Methods and Results: The conventional microelectrode technique was applied in isolated dog cardiac Purkinje and ventricular muscle fibers and in rabbit left atrial muscle. Tedisamil (1 μM) and sotalol (30 μM) lengthened, while quinidine (10 μM) shortened action potential duration in dog Purkinje fibers. The phase 1 repolarization was delayed by tedisamil and quinidine and not changed by sotalol. In dog ventricular muscle and in rabbit atrial muscle, all three drugs studied lengthened repolarization. In dog Purkinje fiber, tedisamil and sotalol lengthened action potential duration more at slow than at high stimulation frequency (reverse use-dependence). In dog ventricular muscle fibers, the effect of the drags was not clearly frequency dependent. In rabbit atrial muscle fibers, the quinidine-evoked repolarization lengthening was most pronounced at intermediate cycle lengths (500-1000 ms). Tedisamil and quinidine but not sotalol depressed the maximal rate of depolarization (V(max)), which depended on the stimulation frequency (use-dependence). The nature of the use-dependent V(max) block differed between quinidine and tedisamil Quinidine decreased V(max) at a relatively wide range of stimulation frequencies while tedisamil decreased V(max) largely at high rate of stimulation. Tedisamil and quinidine prevented or decreased the pinacidil-evoked action potential shortening in dog ventricular muscle, suggesting block of the ATP-dependent potassium channels (I(KATP)), while with sotalol such effect was not observed. Conclusions: Although tedisamil, quinidine, and sotalol are known to lengthen the QT interval, their cellular electrophysiologic effects substantially differ. Tedisamil lengthens repolarization and prevents pinacidil-evoked action potential duration shortening, suggesting I(K)(ATP) blockade. Its effect on the V(max) is limited mostly to fast heart rate. These electrophysiologic effects of tedisamil resemble those of chronic amiodarone treatment.

Original languageEnglish
Pages (from-to)273-284
Number of pages12
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume2
Issue number4
Publication statusPublished - 1997

Fingerprint

Sotalol
Quinidine
Muscles
Dogs
Action Potentials
Pinacidil
Purkinje Fibers
Potassium Channels
Rabbits
Evoked Potentials
tedisamil
Adenosine Triphosphate
Amiodarone
Microelectrodes
Pharmaceutical Preparations

Keywords

  • Action potential duration
  • Electrophysiology
  • Heart
  • Tedisamil

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{a9fee4f76bde42e1a93ae1b0696b4944,
title = "Frequency-dependent cardiac electrophysiologic effects of tedisamil: Comparison with quinidine and sotalol",
abstract = "Background: Tedisamil is a potent bradycardic/antiischemic drug known to lengthen cardiac repolarization by blocking various potassium channels. Recent in vivo experiments revealed that it is an antiarrhythmic agent. It was therefore of interest to compare the cellular electrophysiologic effects of tedisamil with those of quinidine and sotalol in isolated cardiac preparations. Methods and Results: The conventional microelectrode technique was applied in isolated dog cardiac Purkinje and ventricular muscle fibers and in rabbit left atrial muscle. Tedisamil (1 μM) and sotalol (30 μM) lengthened, while quinidine (10 μM) shortened action potential duration in dog Purkinje fibers. The phase 1 repolarization was delayed by tedisamil and quinidine and not changed by sotalol. In dog ventricular muscle and in rabbit atrial muscle, all three drugs studied lengthened repolarization. In dog Purkinje fiber, tedisamil and sotalol lengthened action potential duration more at slow than at high stimulation frequency (reverse use-dependence). In dog ventricular muscle fibers, the effect of the drags was not clearly frequency dependent. In rabbit atrial muscle fibers, the quinidine-evoked repolarization lengthening was most pronounced at intermediate cycle lengths (500-1000 ms). Tedisamil and quinidine but not sotalol depressed the maximal rate of depolarization (V(max)), which depended on the stimulation frequency (use-dependence). The nature of the use-dependent V(max) block differed between quinidine and tedisamil Quinidine decreased V(max) at a relatively wide range of stimulation frequencies while tedisamil decreased V(max) largely at high rate of stimulation. Tedisamil and quinidine prevented or decreased the pinacidil-evoked action potential shortening in dog ventricular muscle, suggesting block of the ATP-dependent potassium channels (I(KATP)), while with sotalol such effect was not observed. Conclusions: Although tedisamil, quinidine, and sotalol are known to lengthen the QT interval, their cellular electrophysiologic effects substantially differ. Tedisamil lengthens repolarization and prevents pinacidil-evoked action potential duration shortening, suggesting I(K)(ATP) blockade. Its effect on the V(max) is limited mostly to fast heart rate. These electrophysiologic effects of tedisamil resemble those of chronic amiodarone treatment.",
keywords = "Action potential duration, Electrophysiology, Heart, Tedisamil",
author = "M. Nemeth and A. Varr{\'o} and L. Vir{\'a}g and O. H{\'a}la and D. Thormahlen and J. Papp",
year = "1997",
language = "English",
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TY - JOUR

T1 - Frequency-dependent cardiac electrophysiologic effects of tedisamil

T2 - Comparison with quinidine and sotalol

AU - Nemeth, M.

AU - Varró, A.

AU - Virág, L.

AU - Hála, O.

AU - Thormahlen, D.

AU - Papp, J.

PY - 1997

Y1 - 1997

N2 - Background: Tedisamil is a potent bradycardic/antiischemic drug known to lengthen cardiac repolarization by blocking various potassium channels. Recent in vivo experiments revealed that it is an antiarrhythmic agent. It was therefore of interest to compare the cellular electrophysiologic effects of tedisamil with those of quinidine and sotalol in isolated cardiac preparations. Methods and Results: The conventional microelectrode technique was applied in isolated dog cardiac Purkinje and ventricular muscle fibers and in rabbit left atrial muscle. Tedisamil (1 μM) and sotalol (30 μM) lengthened, while quinidine (10 μM) shortened action potential duration in dog Purkinje fibers. The phase 1 repolarization was delayed by tedisamil and quinidine and not changed by sotalol. In dog ventricular muscle and in rabbit atrial muscle, all three drugs studied lengthened repolarization. In dog Purkinje fiber, tedisamil and sotalol lengthened action potential duration more at slow than at high stimulation frequency (reverse use-dependence). In dog ventricular muscle fibers, the effect of the drags was not clearly frequency dependent. In rabbit atrial muscle fibers, the quinidine-evoked repolarization lengthening was most pronounced at intermediate cycle lengths (500-1000 ms). Tedisamil and quinidine but not sotalol depressed the maximal rate of depolarization (V(max)), which depended on the stimulation frequency (use-dependence). The nature of the use-dependent V(max) block differed between quinidine and tedisamil Quinidine decreased V(max) at a relatively wide range of stimulation frequencies while tedisamil decreased V(max) largely at high rate of stimulation. Tedisamil and quinidine prevented or decreased the pinacidil-evoked action potential shortening in dog ventricular muscle, suggesting block of the ATP-dependent potassium channels (I(KATP)), while with sotalol such effect was not observed. Conclusions: Although tedisamil, quinidine, and sotalol are known to lengthen the QT interval, their cellular electrophysiologic effects substantially differ. Tedisamil lengthens repolarization and prevents pinacidil-evoked action potential duration shortening, suggesting I(K)(ATP) blockade. Its effect on the V(max) is limited mostly to fast heart rate. These electrophysiologic effects of tedisamil resemble those of chronic amiodarone treatment.

AB - Background: Tedisamil is a potent bradycardic/antiischemic drug known to lengthen cardiac repolarization by blocking various potassium channels. Recent in vivo experiments revealed that it is an antiarrhythmic agent. It was therefore of interest to compare the cellular electrophysiologic effects of tedisamil with those of quinidine and sotalol in isolated cardiac preparations. Methods and Results: The conventional microelectrode technique was applied in isolated dog cardiac Purkinje and ventricular muscle fibers and in rabbit left atrial muscle. Tedisamil (1 μM) and sotalol (30 μM) lengthened, while quinidine (10 μM) shortened action potential duration in dog Purkinje fibers. The phase 1 repolarization was delayed by tedisamil and quinidine and not changed by sotalol. In dog ventricular muscle and in rabbit atrial muscle, all three drugs studied lengthened repolarization. In dog Purkinje fiber, tedisamil and sotalol lengthened action potential duration more at slow than at high stimulation frequency (reverse use-dependence). In dog ventricular muscle fibers, the effect of the drags was not clearly frequency dependent. In rabbit atrial muscle fibers, the quinidine-evoked repolarization lengthening was most pronounced at intermediate cycle lengths (500-1000 ms). Tedisamil and quinidine but not sotalol depressed the maximal rate of depolarization (V(max)), which depended on the stimulation frequency (use-dependence). The nature of the use-dependent V(max) block differed between quinidine and tedisamil Quinidine decreased V(max) at a relatively wide range of stimulation frequencies while tedisamil decreased V(max) largely at high rate of stimulation. Tedisamil and quinidine prevented or decreased the pinacidil-evoked action potential shortening in dog ventricular muscle, suggesting block of the ATP-dependent potassium channels (I(KATP)), while with sotalol such effect was not observed. Conclusions: Although tedisamil, quinidine, and sotalol are known to lengthen the QT interval, their cellular electrophysiologic effects substantially differ. Tedisamil lengthens repolarization and prevents pinacidil-evoked action potential duration shortening, suggesting I(K)(ATP) blockade. Its effect on the V(max) is limited mostly to fast heart rate. These electrophysiologic effects of tedisamil resemble those of chronic amiodarone treatment.

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