Potassium-channel openers or activators have been introduced as a new class of
antihypertensive and antianginal agents that act by increasing membrane conductance to
potassium, mainly through augmentation of the
ATP-sensitive
potassium current. Recent in vitro studies have shown that K(+)-channel openers exert concentration-dependent effects on cardiac electrophysiology. A shortening of the cardiac action potential by acceleration of repolarization has been reported in multicellular preparations as well as in isolated myocytes. However,
drug concentrations that affect the action potential duration of myocardial cells are considerably higher (10- to 100-fold) than those needed for effects on vascular smooth muscle cells. Studies in which mostly high concentrations of K(+)-channel openers were used have demonstrated that these drugs may accelerate automaticity and may promote reentrant activity. Particular interest has focused on the question whether opening of
potassium channels may be potentially arrhythmogenic in the setting of acute
myocardial 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 activity in vivo. The clinical relevance of these experimental studies to the clinical situation is still unclear. Some K(+)-channel openers have been shown to produce electrocardiographic T-wave changes in patients in whom their effectiveness as
antihypertensives was tested. However, this effect was not associated with adverse effects and has not been demonstrated for all compounds.(ABSTRACT TRUNCATED AT 250 WORDS)