Influence of hypoglycaemic sulphonylureas on the electrophysiological parameters of the heart

The effects of different ATP-sensitive potassium channel blocker sulphonylurea drugs (0.01-1000 mumol/l, or kg) were investigated in vitro on the electrical threshold, conduction time, effective refractory period and automaticity of left atrium, right ventricle and Purkinje fibers as well as in vivo on strophanthidin-, ischaemia- and reperfusion-induced arrhythmias and on vagal nerve stimulation in rabbits, rats and dogs. They proved to exert different actions not only quantitatively but also qualitatively. In vitro, glibenclamide diminished the electrical activity of the heart muscle preparations, while chlorpropamide stimulated it, whereas glimepiride does not seem to affect it markedly. In vivo, glibenclamide and glimepiride decrease, while gliclazide and tolbutamide increase, the amount of strophanthidin- and ischaemia-induced ventricular ectopic beats and the duration of ventricular fibrillation. In the case of glimepiride the effect was dependent on the metabolic state. The different actions of sulphonylureas on the electrophysiological properties of the heart cannot be explained solely by their ATP-dependent potassium channel blocking potencies.