It is not clear whether activation of
ATP-sensitive potassium channels (K(
ATP)) with
pinacidil in advance of
ischemia and reperfusion promotes or suppresses arrhythmias. This study determines the effects of
pinacidil pretreatment on arrhythmias and the changes in cellular electrophysiological parameters in segments of guinea pig right ventricular free walls exposed to simulated
ischemia and reperfusion.
Microelectrode recordings were made from endo- and epicardium during endocardial pacing. Preparations were superfused with
Tyrode's solution and then exposed for 5 min to either 100 muM
pinacidil or its
solvent. After a 5-min washout, preparations were exposed to 15 min of ischemic conditions (
hypoxia,
hypercapnia,
hyperkalemia,
acidosis,
lactate accumulation, and
glucose-free) followed by reperfusion with
Tyrode's solution.
Pinacidil pretreatment increased
ischemia-induced abbreviation of endo- and epicardial action potential durations and effective refractory periods.
Pinacidil had no effect on endocardial conduction times but greatly prolonged transmural conduction during
ischemia and early reperfusion, and it increased the incidence of transmural conduction block.
Pinacidil pretreatment caused a significant increase in the incidence of arrhythmias in
ischemia and reperfusion. Reperfusion arrhythmias in control preparations had electrophysiological characteristics of activity initiated by afterpotentials; however, arrhythmias with these characteristics were absent in
pinacidil-pretreated preparations, and all reperfusion arrhythmias exhibited characteristics of reentry. The increased incidence of re-entrant arrhythmias is likely explained by
pinacidil-induced reduction in effective refractory periods in combination with prolonged transmural conduction times. Thus,
pinacidil pretreatment enhanced the effects of
ischemia and reperfusion on action potential duration, effective refractory period, and transmural conduction, and it promoted re-entrant arrhythmias.