Effects of diet-induced hypokalaemia on the antiarrhythmic and electrophysiological actions of prolonged oral treatment with either amiodarone or disopyramide in the anaesthetised rat.
The potential antiarrhythmic and electrophysiological effects of prolonged oral dosing with amiodarone (20 mg/kg/day) or disopyramide (25 or 50 mg/kg b.i.d.) were compared in normokalaemic (NK) and diet-induced hypokalaemic (HK) anaesthetised rats. In NK rats, amiodarone reduced the number of electrical deaths consequent upon coronary artery ligation and prolonged action potential duration (APD50) of papillary muscle. Disopyramide conferred marked protection against arrhythmias in NK animals, prolonged APD50, reduced the maximum rate of depolarisation, and induced bradycardia. Hypokalaemia inhibited both the antiarrhythmic efficacy and these electrophysiological actions of amiodarone and disopyramide. However, prolongation of APD90 by both drugs was little affected by hypokalaemia. Amiodarone prolonged QTc both in NK and HK rats, whilst disopyramide only prolonged QTc in NK rats and only at the higher dose. It is concluded that reduced antiarrhythmic efficacy of the two drugs by hypokalaemia may be due to altered electrophysiological responses. QTc prolongation per se appears to be associated with antiarrhythmic, not arrhythmogenic, actions in this experimental model.
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D004206:Disopyramide / Q000494:pharmacology*; D004562:Electrocardiography; D004594:Electrophysiology; D007008:Hypokalemia / Q000503:physiopathology*; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D004206:Disopyramide; D000638:Amiodarone