Effects of diltiazem therapeutic plasma levels on cardiac conduction and refractoriness.

The effects of diltiazem, a new slow channel inhibitor, on the cardiac conduction and refractoriness have been studied using His bundle recordings and the extrastimulus method. In order to determine the role played by possible changes in vagal tone, diltiazem (0.15 mg.kg-1, followed immediately by a 30 min infusion of 0.01 mg.kg-1.min-1) has been administered intravenously to six atropinized dogs, anesthetized with chloralose (100 mg.kg-1) ("atropine group") and to six others which were given chloralose (80 mg.kg-1) and dextromoramide (0.1 mg.kg-1) to ensure the persistence of vagal tone ("vagal tone group"). In the "atropine group", atrioventricular (AV) nodal conduction time increased by 137% and AV node effective refractory period by 55%. Heart rate was slowed down by 15% and arterial pressure fell slightly. In the "vagal tone group", the only significant changes were a 26% increase in AV nodal conduction time and a slight fall in arterial pressure. Inhibition of the slow channel accounts for the effects of diltiazem within the "atropine group". A reflex decrease in vagal tone is probably responsible for the somewhat different results observed in the "vagal tone group". Diltiazem resembles verapamil and should share its antiarrhythmic properties.