Assessment of the antiarrhythmic activity of nicorandil during myocardial ischemia and reperfusion.
The potential pro- and antiarrhythmic effects of nicorandil (1-100 microM) were assessed in isolated rat hearts subjected to coronary artery ligation and reperfusion under conditions of normal (5.9 mM) and lowered (3.2 mM) perfusate K+. Nicorandil dose dependently increased coronary flow, induced a moderate negative inotropic effect but had no chronotropic effects. During ligation (15 min), only high concentrations of nicorandil (50 and 100 microM) significantly reduced the incidence of ventricular premature beats and ventricular tachycardia in normal perfusate, but ventricular fibrillation was observed in 2/9 hearts. No antiarrhythmic effects were observed with hypokalemic conditions. During reperfusion, nicorandil was associated with a more rapid degeneration into ventricular fibrillation in normal perfusate while the incidence of ventricular fibrillation was only reduced by 100 microM nicorandil. No antiarrhythmic effects were observed during reperfusion with lowered K+ and all drug-treated hearts demonstrated irreversible ventricular fibrillation. Nicorandil perfusion (50 microM; 5.9 mM K+) did not affect the depression of ATP or elevation of lactate within the ischemic tissue during coronary artery ligation. These data do not support an effect of nicorandil against ischemia- or reperfusion-induced arrhythmias in the intact heart in vitro and may suggest a proarrhythmic effect particularly at lowered K+ concentrations.
Kempsford
R D
RD
Department of Physiology, King's College, University of London, U.K.
Hawgood
B J
BJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004562:Electrocardiography; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D007773:Lactates; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate