Investigation of the antifibrillatory drug interactions between Amiodarone and Ibutilide in isolated, perfused Rabbit hearts

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Abstract

In view of the reliability of the serial-shock method of measuring ventricular fibrillation threshold (VFT) in quantitatively assessing the antifibrillatory potency of many anti-arrhythmic drugs and the alarming reports of the proarrhythmic effects of several anti-arrhythmic agents, it was decided to use the above technique to study the possible interactions that may occur when anti-arrhythmic drugs from different classes are combined. Hearts isolated from New Zealand white rabbits of either sex weighing 1.5–2 kg were perfused by the Langendorff method with McEwen's solution. In six hearts, measurement of VFT was made in the absence of any drug throughout the experiments. Perfusion with either amiodarone or ibutilide produced significant, dose-dependent increase in VFT. In addition, there was no significant difference in the increase in VFT produced by the combined infusion of 1 μmol of amiodarone and 0.01 μmol of ibutilide and the summation of the increases produced by the separate infusion of these two concentrations. This is in contrast to a significant synergistic antifibrillatory effect of the combined use of lidocaine and propranolol that was reported previously. The lack of antifibrillatory interactions between amiodarone and Ibutilide may suggest the safety of combining the two drugs in the treatment of cardiac arrhythmias. However, further studies are required to establish this in the clinical setup.

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