- Email: [email protected]
UTILITY OF BEAT-TO-BEAT VARIABILITY OF VENTRICULAR REPOLARIZATION IN ANALYZING PROARRHYTHMIC POTENTIAL OF IKr BLOCKERS
Meeting abstracts
e37
UTILITY OF BEAT-TO-BEAT VARIABILITY OF VENTRICULAR REPOLARIZATION IN ANALYZING PROARRHYTHMIC POTENTIAL OF IKr BLOCKERS Akira Takahara, Yuji Nakamura, Atsushi Sugiyama Department of Pharmacology, University of Yamanashi, Yamanashi, Japan The utility of the beat-to-beat variability of ventricular repolarization speed, an index of temporal heterogeneity, was assessed using the canine chronic atrioventricular block model with typical IKr blockers. Histamine H1 blocker terfenadine (30 mg/kg, n = 6), class III antiarrhythmic drug D-sotalol (30 mg/kg, n = 4) or amiodarone (200 mg/day for initial 7 days and 100 mg/day for the following 21 days, n = 6), was orally administered to the atrioventricular block dogs. For beat-to-beat analysis, ECG of 51 consecutive beats under stable idioventricular automaticity was recorded before and after the drug administration, and Poincarè plots with QTn versus QTn+1 were prepared for each time points. The mean orthogonal distance from the diagonal to the points of the Poincarè plot was adopted as a short-term variability. Terfenadine, D-sotalol and amiodarone significantly prolonged the QT interval by + 55 ms, +30 and + 27, respectively. Torsades de Pointes arrhythmias were induced in 5 out of 6 animals by terfenadine and in all animals by D-sotalol, whereas such arrhythmia was not observed in the amiodarone group. Moreover, changes in short-term variability of repolarization in the terfenadine group (+ 2.0 ms) and D-sotalol group (+ 1.0 ms) were greater than that in the amiodarone group (− 0.2 ms). These results suggest that beat-to-beat variability of ventricular repolarization become a useful predictive marker for the onset of drug-induced Torsades de Pointes arrhythmias. doi:10.1016/j.vascn.2007.02.074
PSEUDO QT-INTERVAL PROLONGATION INDUCED BY ST-SEGMENT DEPRESSION Masaki Saitoh, Akira Takahara, Kiyotaka Hoshiai, Tomomichi Ishizaka, Hiroshi Iwasaki, Yuji Nakamura, Atsushi Sugiyama Department of Pharmacology, University of Yamanashi, Yamanashi, Japan Drugs that affect coronary circulation often alter the morphology of ST-segment of the electrocardiogram (ECG). In this study, we evaluated the effects of a coronary vasodilator dipyridamole on the ventricular repolarization phase using the halothane-anesthetized in vivo canine model under the monitoring of the surface lead II ECG and monophasic action potential (MAP). Intravenous administration of 0.56 mg/kg of dipyridamole, which is a standard dose of the dipyridamole stress test, decreased the mean blood pressure and total peripheral vascular resistance by 12 mm Hg and 17 mm Hg/(l/min), respectively, increased the cardiac output by 0.23 l/min, prolonged the sinus node recovery time, Wenckebach type of atrioventricular block-pacing cycle length and QT interval by 56, 18 and 23 ms, respectively, and depressed the ST-segment by 0.22 mV. However, no significant change was detected in the MAP duration of the right ventricle. These results suggest that drug-induced ST-segment depression might result in a QT interval prolongation in disguise. Thus, the simultaneous assessment of the MAP and QT interval may be an effective way to better analyze the effects of coronary vasodilators on the repolarization process. doi:10.1016/j.vascn.2007.02.075
e37
UTILITY OF BEAT-TO-BEAT VARIABILITY OF VENTRICULAR REPOLARIZATION IN ANALYZING PROARRHYTHMIC POTENTIAL OF IKr BLOCKERS Akira Takahara, Yuji Nakamura, Atsushi Sugiyama Department of Pharmacology, University of Yamanashi, Yamanashi, Japan The utility of the beat-to-beat variability of ventricular repolarization speed, an index of temporal heterogeneity, was assessed using the canine chronic atrioventricular block model with typical IKr blockers. Histamine H1 blocker terfenadine (30 mg/kg, n = 6), class III antiarrhythmic drug D-sotalol (30 mg/kg, n = 4) or amiodarone (200 mg/day for initial 7 days and 100 mg/day for the following 21 days, n = 6), was orally administered to the atrioventricular block dogs. For beat-to-beat analysis, ECG of 51 consecutive beats under stable idioventricular automaticity was recorded before and after the drug administration, and Poincarè plots with QTn versus QTn+1 were prepared for each time points. The mean orthogonal distance from the diagonal to the points of the Poincarè plot was adopted as a short-term variability. Terfenadine, D-sotalol and amiodarone significantly prolonged the QT interval by + 55 ms, +30 and + 27, respectively. Torsades de Pointes arrhythmias were induced in 5 out of 6 animals by terfenadine and in all animals by D-sotalol, whereas such arrhythmia was not observed in the amiodarone group. Moreover, changes in short-term variability of repolarization in the terfenadine group (+ 2.0 ms) and D-sotalol group (+ 1.0 ms) were greater than that in the amiodarone group (− 0.2 ms). These results suggest that beat-to-beat variability of ventricular repolarization become a useful predictive marker for the onset of drug-induced Torsades de Pointes arrhythmias. doi:10.1016/j.vascn.2007.02.074
PSEUDO QT-INTERVAL PROLONGATION INDUCED BY ST-SEGMENT DEPRESSION Masaki Saitoh, Akira Takahara, Kiyotaka Hoshiai, Tomomichi Ishizaka, Hiroshi Iwasaki, Yuji Nakamura, Atsushi Sugiyama Department of Pharmacology, University of Yamanashi, Yamanashi, Japan Drugs that affect coronary circulation often alter the morphology of ST-segment of the electrocardiogram (ECG). In this study, we evaluated the effects of a coronary vasodilator dipyridamole on the ventricular repolarization phase using the halothane-anesthetized in vivo canine model under the monitoring of the surface lead II ECG and monophasic action potential (MAP). Intravenous administration of 0.56 mg/kg of dipyridamole, which is a standard dose of the dipyridamole stress test, decreased the mean blood pressure and total peripheral vascular resistance by 12 mm Hg and 17 mm Hg/(l/min), respectively, increased the cardiac output by 0.23 l/min, prolonged the sinus node recovery time, Wenckebach type of atrioventricular block-pacing cycle length and QT interval by 56, 18 and 23 ms, respectively, and depressed the ST-segment by 0.22 mV. However, no significant change was detected in the MAP duration of the right ventricle. These results suggest that drug-induced ST-segment depression might result in a QT interval prolongation in disguise. Thus, the simultaneous assessment of the MAP and QT interval may be an effective way to better analyze the effects of coronary vasodilators on the repolarization process. doi:10.1016/j.vascn.2007.02.075