Protective effects of nicorandil on action potentials in anoxia and reoxygenated ventricular myocardium of guinea pig

Standard microelectrode techniques were used to study the effects of nicorandil (500 mumol.L-1) on action potentials in anoxia and reoxygenated ventricular myocardium of guinea pig. The main results: (a) Nicorandil shortened the action potentials duration (APD) and increased the ratio of effective refractory period (ERP) to APD90 (ERP/APD90). It did not cause significant changes in resting potential (RP), the maximal rate of rise of phase 0 (Vmax) and action potential amplitude (APA); (b) Exposure of the preparation to anoxic conditions (hypoxia, acidosis, glucose deprivation, and hyperkalemia) for 20 min, resulted in a marked depolarization of RP, a shortening of APD, reductions of APA and Vmax, and an increase in the ratio of ERP/APD90; (c) Nicorandil did not produce any additional effect on these parameters during anoxia except aggravated shortening of APD; (d) The changes of action potential parameters during anoxia were all completely reversed when the preparation was reoxygenated in the absence of the drug for 20 min. In the presence of the drug, however, APD was only partially reversed; (e) Nicorandil decreased the incidence of abnormal automaticity occurring during reoxygenation from 14/16 to 4/16. It is concluded that nicorandil antagonizes the cellular mechanisms which underlie the reoxygenation arrhythmias and prevent the reoxygenation-induced arrhythmias.