title: Electrophysiological effects of flecainide on guinea pig ventricular muscle in high [K+]o, acidosis and hypoxia.
abstract: The electrophysiological effects of flecainide on the action potential were examined in guinea pig ventricular muscles using microelectrode recording methods. Under the control conditions, flecainide (0.5-1 microgram/ml) did not alter the resting potential, action potential duration (APD) or effective refractory period (ERP). The major effect of flecainide was on maximum upstroke velocity (Vmax), which was depressed in a dose-dependent manner. In high [K+] medium (potassium concentration = 10 mM), Vmax was depressed by 16.8% at a concentration of 1.0 microgram/ml (8.8% in normal [K+]o). In metabolic acidosis (pH = 6.89), it was depressed by 15.7% at the same concentration of the drug (8.3% in normal condition). The changes in ERP and ERP/APD90% in high [K+]o and metabolic acidosis were not significantly different from the normal condition. After hypoxic perfusion for 15 min, Vmax depression by flecainide was 16.3% (7.4% in control medium). The increase of ERP/APD90% was also greater in hypoxia. These data indicate that the most prominent effect of flecainide is Vmax depression which is enhanced under the high K+, acidic and hypoxic conditions. Therefore, it is suggested that flecainide may be most effective for ventricular arrhythmias occurring in myocardial ischemia.
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D003327:Coronary Disease / Q000188:drug therapy; D005260:Female; D005424:Flecainide / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D005424:Flecainide; D011188:Potassium