Antiarrhythmic and electrophysiological effects of amiodarone, lignocaine, and penticainide in anaesthetised rats.
OBJECTIVE
The aim was to correlate the relative abilities of amiodarone, lignocaine, and penticainide in suppressing ventricular tachyarrhythmias in response to coronary artery occlusion with their relative abilities to prolong ventricular functional refractory periods and to reduce intraventricular conduction velocities in anaesthetised open chest rats.


METHODS
Functional refractory period was measured with a paired electrical stimulation technique. Intraventricular conduction velocity was monitored using the QRS duration of the ECG.


RESULTS
Low doses of these three drugs were selected which protected against ventricular tachyarrhythmias induced by coronary occlusion. These doses prolonged the functional refractory period without increasing QRS duration. High doses of both amiodarone and lignocaine were more effective than low doses in suppressing coronary occlusion induced ventricular tachyarrhythmias. Such high doses greatly prolonged the functional refractory period but prolonged the QRS duration only moderately. In contrast, higher doses of penticainide failed to inhibit coronary occlusion induced ventricular tachyarrhythmias. These higher doses of penticainide prolonged the functional refractory period but prolonged the QRS duration even more markedly.


CONCLUSIONS
Among these three drugs an increase in functional refractory period appears to be antiarrhythmic. In contrast, widening of the QRS complex without a corresponding increase in functional refractory period, as produced by penticainide, appears to counteract the antiarrhythmic effect.
Li
J Y
JY
Department of Pharmacology, School of Pharmacy, Leicester Polytechnic, United Kingdom.
Northover
B J
BJ
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D011437:Propylamines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time
D000889:Anti-Arrhythmia Agents; D011437:Propylamines; D011725:Pyridines; C045930:propisomide; D008012:Lidocaine; D000638:Amiodarone