ELECTROPHYSIOLOGIC EFFECTS OF POTASSIUM CHANNEL OPENERS

Potassium-channel openers or activators have been introduced as a new class of antihypertensive and antianginal agents that act by increasin g membrane conductance to potassium, mainly through augmentation of th e ATP-sensitive potassium current. Recent in vitro studies have shown that K+-channel openers exert concentration-dependent effects on cardi ac electrophysiology. A shortening of the cardiac action potential by acceleration of repolarization has been reported in multicellular prep arations as well as in isolated myocytes. However, drug concentrations that affect the action potential duration of myocardial cells are con siderably higher (10- to 100-fold) than those needed for effects on va scular smooth muscle cells. Studies in which mostly high concentration s of K+-channel openers were used have demonstrated that these drugs m ay accelerate automaticity and may promote reentrant activity. Particu lar interest has focused on the question whether opening of potassium channels may be potentially arrhythmogenic in the setting of acute myo cardial ischemia. On the other hand, recent studies have shown that K-channel openers are effective in suppressing polymorphic ventricular tachyarrhythmias induced by early afterdepolarizations and triggered a ctivity in vivo. The clinical relevance of these experimental studies to the clinical situation is still unclear. Some K+-channel openers ha ve been shown to produce electrocardiographic T-wave changes in patien ts in whom their effectiveness as antihypertensives was tested. Howeve r, this effect was not associated with adverse effects and has not bee n demonstrated for all compounds. So far the worsening of existing arr hythmias or the induction of new arrhythmias by K+-channel openers in humans has not been reported.