IN-VIVO AND IN-VITRO ELECTROPHYSIOLOGIC EFFECTS OF TERODILINE ON DOG MYOCARDIUM

Introduction: Terodiline hydrochloride, widely prescribed for urinary incontinence, has been reported to cause bradycardia and torsades de p ointes. Methods and Results: In this study, we characterized the elect rophysiologic effects of terodiline in dog cardiac tissues in vivo and in isolated canine cardiac Purkinje fibers. Terodiline (1 to 10 mu M) resulted in dose-dependent reduction of action potential amplitude an d maximal upstroke velocity (V-max). The threshold for these effects w as similar to 2 mu M (0.6 mg/L), and the changes were cycle-length dep endent. Terodiline (greater than or equal to 2 mu M) also depressed th e action potential plateau but did not significantly alter action pote ntial duration at concentrations less than or equal to 10 mu M. In viv o studies demonstrated that high doses of terodiline (3 mg/kg) lengthe ned AH and HV intervals, slowed spontaneous sinus rate, prolonged vent ricular refractoriness, and inhibited vagally induced slowing of the s inus node. Sympathetic effects on spontaneous sinus rate were unchange d. In both isolated canine Purkinje fibers and anesthetized dogs, tero diline did not evoke afterdepolarizations, repetitive firing, or ventr icular tachyarrhythmias under normal or hypokalemic conditions. Conclu sion: Our findings suggest that terodiline (greater than or equal to 1 to 2 mu M) leads to blockade of sodium and calcium channels as well a s muscarinic receptors in canine cardiac tissues.