© 1992 by European Society of Cardiology
Copyright © 1992, European Society of Cardiology
Effects of intravenous amiodarone on electrical dispersion in normal and ischaemic tissues and on arrhythmia inducibility: monophasic action potential studies
Reingold ECG Center (Section of Cardiology), Department of Medicine, Northwestern University Medical School, 303 E Chicago Avenue, Chicago, IL 606 1 1, USA: R D Mayuga, D H Singer.
Correspondence to Dr Mayuga.
Objective: The aim was to study the effects of intravenous amiodarone on: (1) repolarisation and other monophasic action potential characteristics of normal and ischaemic tissues, and (2) vulnerability to pacing induced repetitive ventricular firing following acute left anterior descending coronary artery ligation. Methods: Epicardial monophasic action potentials were continuously and simultaneously recorded from ischaemic and non-ischaemic regions of the hearts of 24 pentobarbitone anaesthetised dogs. Monophasic action potential duration, rise time, and amplitude, as well as the degree of dispersion of repolarisation between normal and ischaemic areas and vulnerability to electrical induction of repetitive ventricular firing, were determined using hand held silver-silver chloride "contact pressure" electrodes, before and 15 min after coronary ligation; and 15 min after exposure to low (10 mg·kg–1) doses of amiodarone. Similar determinations were made in drug free controls. Results: Under control conditions, monophasic action potentials from both the (potentially) ischaemic and non-ischaemic regions were comparable, dispersion of repolarisation was minimal, and repetitive ventricular firing could not be induced. Coronary ligation significantly decreased monophasic action potential duration and increased rise time in the ischaemic, but not in the non-ischaemic, regions. Dispersion of repolarisation increased markedly. Repetitive ventricular firing could be induced in all dogs. "Low dose" amiodarone caused a much greater prolongation of repolarisation duration at ischaemic than at non-ischaemic sites. Dispersion of repolarisation decreased virtually to control levels and repetitive firing could no longer be induced in six of seven dogs. "High dose" amiodarone increased ischaemic region repolarisation duration and rise time relative to the non-ischaemic region to an even greater extent than the "low" dose, with the result that dispersion of repolarisation increased rather than decreased and repetitive ventricular firing again became inducible. Conclusions: The data indicate that: (1) intravenous amiodarone prolongs repolarisation of ischaemic tissues to a greater extent than that of normal tissues; (2) "low" dose amiodarone resulted in an overall decrease in dispersion of repolarisation, with little or no change in dispersion of rise time; (3) the "high" dose increased dispersion of both repolarisation and rise time. These changes were paralleled by changes in vulnerability to induction of repetitive ventricular firing by programmed ventricular pacing, the "low" dose being associated with decreases, and the "high" dose with further increases, in vulnerability, respectively.
KEYWORDS monophasic action potentials; amiodarone; dispersion of repolarisation
The authors wish to express their appreciation to Dr Michael Franz for his help with the initial development of the technique in the laboratory, and to Drs James E Rosenthal, Masao Nishimura, Helge Rasmussen, J Andrew Wasserstrom, Christopher Follmer and Robert E Ten Eick for their critical comments. Supported in part by Grants-in-Aid from the Reingold Estate, the Brinton Trust, and the Cooley Charitable Trust.
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