ASSA14-03-47 Ivabradine prolongs action potential duration and causes atrial arrhythmia in the heart

Abstract

Objective Ivabradine (IVA) selectively inhibits I f current in the sinus node and is used to treat inappropriate sinus tachycardia. Previous studies indicated that IVA also inhibited I Kr at concentrations higher than therapeutic range. However, the proarrhythmic risk of IVA has not been fully determined. Sea anemone toxin (ATX) –II treated hearts have an increased risk of proarrhythmia and therefore was used to detect low-risk QT prolonging drugs. The objective of this study was to determine the effect of IVA on the atrial and ventricular monophasic action potential duration (MAPD) and the arrhythmic activities in the absence and presence of ATX-II. Methods Female rabbit isolated hearts were perfused by Langendorff mode. Hearts were paced at right atria appendage, and left atrial and ventricular MAPD 90 were recorded and analysed. Results When hearts were paced at 2.8 Hz, the atrial, and endocardial and epicardial ventricular MAPD 90 were 49.6 ± 3, 136.3 ± 7 and 127.4 ± 4 ms. IVA (3–10 μm) significantly prolonged them by 15.9 ± 2 (n = 6, p 90 by 41.2 ± 3 and 31.6 ± 4 ms (n = 5, p 90 by 36.5 ± 5 ms, and LV endocardial and epicardial MAPD 90 by 19.9 ± 3 and 19.5 ± 4 ms. In the continued presence of ATX-II (3 nM), IVA (6–10 μm) reduced the atrial MAPD 90 by 14.4 ± 4 ms (n = 6, p 90 by 36.2 ± 7 and 27.5 ± 5 ms (n = 6, p 90 and transmural dispersion of MAPD 90 , and caused no ventriculararrhythmia both in the absence and presence of ATX-II, (n = 6, p > 0.05; n = 6, p > 0.05) . Conclusion IVA prolongs both atrial and ventricular MAPD and causes atrial arrhythmias in hearts when late sodium current is increased, without proarrhythmic activities in the ventricles. This result may explain the results in clinical research.