Effects of Verapamil and Pinacidil on Extracellular K+, pH, and the Incidence of Ventricular Fibrillation during 60 Minutes of Ischemia.

Abstract

Ca++-channel antagonist verapamil and ATP-sensitive K+-channel opener pinacidil are known to decrease the rise in extracellular K+ ([K+]e) level and pH (pHe) that occurs during reversible acute myocardial ischemia and to lessen the accompanying activation delay. Verapamil is also known to decrease the incidence of ventricular tachycardia (VT)/fibrillation (VF) during acute myocardial ischemia; however, the effects of ATP-sensitive K+-channel opener on the incidence of VT/VF are controversial. We studied, in an in vivo pig model, the effects of verapamil and pinacidil on the changes in [K+]e level and pHe, local activation, and the incidence of VT/VF during 60 minutes of ischemia. Thirty-one pigs were divided into 2 groups: a verapamil group (9 control pigs and 8 verapamil-treated pigs) and pinacidil group (5 control pigs and 9 pinacidil-treated pigs). In the verapamil group, VF developed in 1 of the 9 control pigs, whereas no VF developed in 8 verapamil-treated pigs. In the pinacidil group, VF developed in 3 of the 5 control pigs and all 9 pinacidil-treated pigs. Under verapamil treatment (versus the control condition), onset of the second rise in [K+]e level was delayed, and the maximum rise in [K+]e level was decreased. Under pinacidil treatment (versus the control condition), time to the onset of VT/VF was shorter than that under the control condition, and VT/VF developed at lower [K+]e level and higher pHe. In conclusion, VF may develop at a lesser [K+]e rise and pHe fall in the presence of pinacidil during acute myocardial ischemia.