Pinacidil-induced electrical heterogeneity and extrasystolic activity in canine ventricular tissue. Does activation of ATP-regulated potassium current promote phase 2 reentry? CircuZation 88

Background. Pinacidil is known to augment a time-independent outward current in cardiac tissues by activating the ATP-regulated potassium channels. Activation of this current, IK.ATP, is thought to be responsible for increased potassium permeability in ischemia. The contribution of IK.ATP activation to arrhythmogenesis and the role of activation of this current in suppression of arrhythmias are areas of great interest and debate. Because electrical depression attending myocardial ischemia is more accentu-ated in ventricular epicardium than in endocardium, we endeavored to contrast the effects of pinacidil-induced IK.ATP activation on the electrophysiology of canine ventricular epicardium and endocardium. Methods and Results. Standard microelectrode techniques were used. Pinacidil (1 to 5 umol/L) produced a marked dispersion of repolarization and refractoriness in isolated canine ventricular epicardium as well as between epicardium and endocardium. In endocardium, pinacidil abbreviated action potential duration (APD,0) and refractoriness by 8.0±2.3%. In epicardium, the effects of pinacidil were nonhomo-geneous. At some sites, pinacidil induced an all-or-none repolarization at the end of phase 1 of the action potential, resulting in 55.5±8.7 % abbreviation ofAPD,0 and refractoriness. Adjacent to these were sites at which the dome was maintained with only minor changes in APD and refractoriness. Extrasystolic activity displaying features of reentry was observed in isolated sheets of epicardium (63.2%) after exposure t