Acute Electrophysiologic and Blood Pressure Effects of Amiodarone and its Solvent in the Dog

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Abstract
Amiodarone has repeatedly been shown to have potent class III antiarrhythmic properties. It has, however, been questioned whether the acute and chronic effects of the drug are due to the same mechanism. In order to investigate the acute electrophysiologic and blood pressure effect of the drug, amiodarone (Cordarone®) was given intravenously in cumulative doses of 2.5, 5.0 and 10.0 mg/kg to seven pentobarbital (mebumalum NFN) anaesthetized dogs. Corresponding volumes of the solvent, polysorbatum 80 (Tween 80), were given to two dogs. Cardiac electrophysiologic effects were studied by His bundle electrography and programmed electrical stimulation. Amiodarone decreased heart rate and AV nodal conduction velocity and increased atrial, AV nodal and ventricular refractoriness. A pronounced but transient fall in mean aortic blood pressure (MABP) occurred after the first injection of amiodarone. No fall in MABP occurred, however, after the subsequent two doses. Intravenous injection of the solvent exactly reproduced the effects on MABP, but not the electrophysiologic effects. The present study supports the concept that amiodarone also has acute class III antiarrhythmic effect. After the initial injection, a pronounced fall in blood pressure due to the solvent may be seen, but rapid tachyphylaxis occurs.