Anti-Arrhythmic Action of an ATP-Sensitive Potassium Channel Blocker Against Atrial Fibrillation Associated with Beta-Adrenergic Stress in Rat Hearts

Abstract

Atrial fibrillation (AF) is the most common disturbance of cardiac rhythm and results in a significantly increased risk of death. Although it is widely accepted that changes to the atrial muscle associated with heart disease make prolonged episodes of AF more likely to occur, the mechanisms underlying the origins of AF remain unclear. It is thought that sympathetic innervation plays an important role in the initiation of paroxysms of AF. ATP-sensitive K+ channels (KATP channels) have been suggested to contribute to myocardial responses to beta-adrenergic stress. To investigate the role of KATP channel opening in the genesis of AF associated with beta-adrenergic stress, we examined the susceptibility to AF of excised Langendorff-perfused hearts from adult male Wistar rats. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a multi-electrode array, allowing measurements of atrial effective refractory period (AERP) and conduction velocity (CV) through the construction of activation maps. Paroxysms of AF were induced by burst pacing and the incidence and duration of the arrhythmia noted. Beta-adrenergic stress was induced by perfusion of the hearts with isoprenaline (ISO). While it was not possible to induce paroxysms of AF in control conditions, perfusion of the hearts with ISO rendered the left atrium susceptible to pacing-induced AF; the incidence and duration of which increased in a concentration-dependent manner. The shortening of AERP and incidence of AF induced by 10−6 M ISO were completely blocked in the presence of the KATP channel blocker, glibenclamide (10−5 M). In the absence of ISO, glibenclamide had no effect on AERP or CV. Taken together, our results suggest that KATP channels can contribute to atrial arrhythmogenesis during beta-adrenergic stress.Supported by the BHF (PG/09/046).