Antiarrhythmic potential of chloroquine: new use for an old drug.
Amiodarone and chlorpromazine are phospholipase inhibitors which produce cytoplasmic inclusion bodies and have important electrophysiologic properties. Chloroquine also inhibits phospholipase activity, resulting in similar inclusion bodies, but electrophysiologic information about this drug is lacking. In this study, the cellular electrophysiologic effects of two doses of chloroquine were examined in sheep Purkinje fibres and ventricular muscle cells. Both concentrations produced a significant reduction in maximum velocity of upstroke of the action potential and prolongation of the action potential duration and refractory period in Purkinje fibres. These effects were observed in the absence of significant changes in threshold of stimulation or action potential amplitude and were partially reversible following washout of the lower drug concentration. In addition to these experimental data, clinical evidence of antiarrhythmic action was determined by administering 500 mg chloroquine daily over nine weeks to six subjects with frequent asymptomatic ventricular premature complexes. In four patients there was a reduction in ventricular ectopy, which recurred when the drug was discontinued, while a fifth patient reverted to sinus rhythm from atrial fibrillation previously resistant to other antiarrhythmic medication. Thus, chloroquine has important electrophysiologic properties. The underlying mechanism of this action remains unproven at the present time.
Harris
L
L
Division of Cardiology, Women's College Hospital, Toronto, Ontario.
Downar
E
E
Shaikh
N A
NA
Chen
T
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D005117:Cardiac Complexes, Premature / Q000517:prevention & control; D002738:Chloroquine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011690:Purkinje Fibers / Q000187:drug effects*; D012756:Sheep
D000889:Anti-Arrhythmia Agents; D002738:Chloroquine