Nicorandil effects on human monophasic action potentials and refractoriness

The EP profile of N has been assessed by conventional EP study (28 pts), and Monophasic Action Potential (MAP) recordings (atrial (RA), 24/28 pts; and ventricular (RV), 1 case with idiopathic long QT interval and ventricular arrhythmias). All pts were studied 15' after sublingual administration of 20 mg N. A-V conduction intervals and A-V nodal effective refractory period (ERP) were not significantly affected by N, whereas atrial ERP, antegrade Wenckebach point and sinus cycle length (SCL) were significantly shortened (p < 0.05). The RA MAP duration (D90%) was unchanged in 9/24, significantly shortened in 12/24, and prolonged in 3/24 pts. Different effects of N on RA MAP could be due to the wide individual plasma level variability observed 15' after a 20 mg sublingual dose. The mechanism for RA MAP prolongation after N (3/24 pts) remains unexplained and needs further investigation. Abnormal corrected sinus node recovery time values in basal condition (6/28 pts) were further prolonged after N in 3/6 pts and shortened in 3/6 pts. In the long-QT patient N induced evident hyperpolarization of RV MAP, did not abolish afterdepolarization-like 'bumps' and increased local differences of repolarization (MAP D90% variation coefficient from 10.8 to 28%).