Electrocardiographic interactions between pinacidil, a potassium channel opener and class I antiarrhythmic agents in guinea-pig isolated perfused heart.

摘要

1. Drugs that shorten action potential duration could decrease the Na-channel blocking effect of class I antiarrhythmic agents by reducing the availability of Na channel in the inactivated state. 2. This hypothesis was tested in guinea-pig perfused heart, measuring the surface ECG effects of three class I drugs endowed with different binding kinetics (15 microM mexiletine, 10 microM quinidine and 3 microM flecainide) in the presence of increasing concentrations of pinacidil (10 microM, 30 microM, 50 microM), a potassium channel opener that shortens action potential duration. 3. The ECG parameters measured were: the QRS interval, i.e. the intraventricular conduction time; the JT interval, which reflects the duration of ventricular repolarization; the ratio between JT peak (the time from the end of QRS and the peak of T wave) and JT interval, which quantifies changes in the morphology of the T wave. 4. At the concentrations tested all the antiarrhythmic drugs widened the QRS complex by 55-60%. Flecainide did not significantly change JT interval, but quinidine prolonged and mexiletine shortened it. Mexiletine also decreased the JTpeak/JT ratio. Pinacidil by itself decreased the JT interval and the JT peak/JT ratio in a dose-dependent way, but did not affect QRS duration. 5. In the presence of fixed antiarrhythmic drug concentrations, however, pinacidil decreased the QRS prolongation induced by mexiletine (-17%) and quinidine (-8%), but not that induced by flecainide: this effect was already maximal at the lower concentration tested (10 microM) and there was no relationship between pinacidil-induced JT shortening and QRS changes.(ABSTRACT TRUNCATED AT 250 WORDS)