In vivo and in vitro electrophysiologic effects of terodiline on dog myocardium

M. L. Pressler, M. R. Warner, Michael Rubart-von der Lohe, D. P. Rardon, D. P. Zipes

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Electrophysiologic Effects of Terodiline. Introduction: Terodiline hydrochloride, widely prescribed for urinary incontinence, has been reported to cause bradycardia and torsades de pointes. Methods and Results: In this study, we characterized the electrophysiologic effects of terodiline in dog cardiac tissues in vivo and in isolated canine cardiac Purkinje fibers. Terodiline (1 to 10 μM) resulted in dose-dependent reduction of action potential amplitude and maximal upstroke velocity (V(max)). The threshold for these effects was ~2 μM (0.6 mg/L), and the changes were cycle-length dependent. Terodiline (≥ 2 μM) also depressed the action potential plateau but did not significantly alter action potential duration at concentrations ≤ 10 μM. In vivo studies demonstrated that high doses of terodiline (3 mg/kg) lengthened AH and HV intervals, slowed spontaneous sinus rate, prolonged ventricular refractoriness, and inhibited vagally induced slowing of the sinus node. Sympathetic effects on spontaneous sinus rate were unchanged. In both isolated canine Purkinje fibers and anesthetized dogs, terodiline did not evoke afterdepolarizations, repetitive firing, or ventricular tachyarrhythmias under normal or hypokalemic conditions. Conclusion: Our findings suggest that terodiline (≥ 1 to 2 μM) leads to blockade of sodium and calcium channels as well as muscarinic receptors in canine cardiac tissues.

Original languageEnglish
Pages (from-to)443-454
Number of pages12
JournalJournal of Cardiovascular Electrophysiology
Volume6
Issue number6
StatePublished - 1995

Fingerprint

Myocardium
Dogs
Action Potentials
Purkinje Fibers
Canidae
Calcium-Sensing Receptors
Torsades de Pointes
Sinoatrial Node
terodiline
In Vitro Techniques
Sodium Channels
Urinary Incontinence
Muscarinic Receptors
Calcium Channels
Bradycardia
Tachycardia

Keywords

  • action potentials
  • electrophysiology
  • Purkinje fibers
  • terodiline
  • torsades de pointes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

In vivo and in vitro electrophysiologic effects of terodiline on dog myocardium. / Pressler, M. L.; Warner, M. R.; Rubart-von der Lohe, Michael; Rardon, D. P.; Zipes, D. P.

In: Journal of Cardiovascular Electrophysiology, Vol. 6, No. 6, 1995, p. 443-454.

Research output: Contribution to journalArticle

Pressler, M. L. ; Warner, M. R. ; Rubart-von der Lohe, Michael ; Rardon, D. P. ; Zipes, D. P. / In vivo and in vitro electrophysiologic effects of terodiline on dog myocardium. In: Journal of Cardiovascular Electrophysiology. 1995 ; Vol. 6, No. 6. pp. 443-454.
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