Lack of selectivity for ventricular and ischaemic tissue limits the antiarrhythmic actions of lidocaine, quinidine and flecainide against ischaemia-induced arrhythmias.
The antiarrhythmic effectiveness, electrocardiographic and haemodynamic properties of three representative class I antiarrhythmics have been investigated in anaesthetized rats. Quinidine, lidocaine and flecainide were chosen as representatives of class Ia, Ib and Ic, respectively. Lidocaine showed the greatest frequency and 'ischaemia' dependency and a high dose provided complete protection against ischaemic arrhythmias induced by coronary artery occlusion. Flecainide showed the least frequency and ischaemia dependency and the least antiarrhythmic effectiveness. Quinidine was only slightly more effective than flecainide. The three drugs were approximately equi-potent in lowering blood pressure which limited the maximum dose that could be tested. The highest dose of lidocaine also caused convulsions in conscious animals. Thus, while lidocaine had selectivity for ischaemic tissue, and for high frequencies, the central nervous system and cardiovascular toxicity limited its usefulness against ischaemia-induced arrhythmias. Quinidine and flecainide's lack of selectivity for ischaemia, and/or high frequencies, probably accounted for their limited antiarrhythmic actions against ischaemia-induced arrhythmias. This study emphasizes that class I drugs can only provide useful protection against ischaemia-induced arrhythmias if they have marked cardiac selectivity as well as selectivity for ischaemic cardiac tissue.
Barrett
T D
TD
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Hayes
E S
ES
Walker
M J
MJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D005424:Flecainide / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D011802:Quinidine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; D011802:Quinidine; D005424:Flecainide