Acute effects of amiodarone upon the canine sinus node and atrioventricular junctional region.

Abstract

A B S T R A C T Amiodarone was selectively perfused into the sinus node artery and atrioventricular node artery of 51 dogs. Amiodarone had an immediate negative chronotropic and dromotropic effect. Threshold concentration was 2.5 ug/ml. 25 and 50 Ag/ml of amiodarone injected into the sinus node artery slowed the heart by 25.6±3.1 and 33.7±2.6 beats/min (mean±1 SEM), respectively. Amiodarone 25 and 50 ,g/ml injected into the AV node artery during AV junctional rhythm slowed the AV junctional pacemaker by 12.2±1.8 and 17.4±1.7 beats/min, respectively. Injections of amiodarone into the AV node artery during sinus rhythm regularly increased AV conduction time sometimes causing 20 AV block at the highest concentration used. Impaired conduction was exclusively measured at the level of the A-H interval in the His electrogram. Neither atropine nor propranolol prevented the negative chronotropic effects of amiodarone. Amiodarone had no significant effect on sinus node response to either stellate stimulation or intranodal administration of norepinephrine. The negative chronotropic action of amiodarone was significantly enhanced when amiodarone was administered in a perfusate containing low (0.6 mM) instead of normal calcium. Taken collectively these observations indicate that amiodarone has immediate depressant electrophysiologic effects on both the sinus node and the AV junction and that these early effects might involve the blockade of the slow channel.

Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?

“…Therefore, amiodarone must have a very peculiar action on the impulse forming system of the heart, since it seems to have a desensitizing effect on several pharmacological agents which have different mechanisms of action. It is not surprising that amiodarone has recently been shown to possess, besides its weak aand P-blocking properties (Charlier et al, 1967;Polster & Broekhuysen, 1976), a slow-calciumchannel blocking action (Gloor et al, 1983). The ultimate mode of action of the potent antiarrhythmic drug amiodarone still remains far from clear.…”

Clinical electrophysiologic effects of a single high oral dose of amiodarone

“…In the present study sinus node hnction was not depressed and Holter monitoring did not show major bradycardia. Experimental studies (Gloor et al, 1983;Goupil and Lenfant, 1976) suggest a depression of sinus node automaticity by acute amiodarone administration. This effect has not been fully investigated in man and appears to be variable (Singh.…”

Assessment of Amiodarone Effects on Intact Cats? Electrocardiograms (ECG)

“…Although SA arrest was not seen in this study, induction of bradycardia, especially at high doses, was pronounced. This showed amiodarone's potential effects on SA and AV nodes or ventricular functions (9,19,20).…”

“…, and potassium (K + ) channels and heart automaticity (9,19,20). Furthermore, these alterations can be induced by amiodarone blocking effects on cardiac β-receptors because of its β-blocker properties (18,(20)(21)(22).…”