Effects of Diet-Induced Hypokalaemia on the Efficacy of Antiarrhythmic Drugs Against Ventricular Arrhythmias Evoked by Coronary Artery Ligation in the Anaesthetised Rat

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Abstract
The antiarrhythmic efficacies of intravenous quinidine (Q), disopyramide (D), prenylamine (P), bepridil (B), and practolol were compared in normokalaemic and dietary-induced hypokalaemic anaesthetized rats. Hypokalaemia markedly incresed the severity of arrhythmias induced by coronary artery ligation and reduced the antiarrhythmic efficacy of all five drugs tested. After anaesthesia, hypokalaemia was associated with hypotension and bradycardia but not QTc prolongation. However, bradycardia was not seen in conscious hypokalaemic animals. Papillary muscles taken from hypokalaemic rats displayed a longer action potential duration but not increase in .ovrhdot.Vmax compared with tissue taken from normokalaemic animals. It is concluded that hypokalaemia in the rat causes electrophysiological disturbances which may contribute both to the observed exacerbation of ischaemia-induced arrhythmias and to the reduced efficacy of Q, D, P, and B. The reduced efficacy of practolol might be explained by other consequences of hypokalaemia.