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In Vivo and In Vitro Electrophysiologic Effects of Terodiline on Dog Myocardium
Author(s) -
PRESSLER MILTON L.,
WARNER MARGARET R.,
RUBART MICHAEL,
RARDON DAVID P.,
ZIPES DOUGLAS P.
Publication year - 1995
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1995.tb00418.x
Subject(s) - medicine , afterdepolarization , purkinje fibers , carnivora , refractory period , fissipedia , effective refractory period , bradycardia , in vivo , endocrinology , sinoatrial node , electrophysiology , torsades de pointes , sinus bradycardia , cardiology , heart rate , anesthesia , qt interval , biology , microbiology and biotechnology , blood pressure , repolarization
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.