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Acta Physiologica 2012; Volume 205, Supplement 690
Joint Meeting of the Hungarian Biophysical Society, Hungarian Physiological Society, Hungarian Society of Anatomists and Hungarian Society of Microcirculation & Vascular Biology
6/11/2012-6/13/2012
Debrecen, Hungary
CLASS I ANTIARRHYTHMICS AT THERAPEUTIC CONCENTRATIONS DO NOT INCREASE ELECTRICAL INSTABILITY DURING ACUTE ISCHAEMIA
Abstract number: P18
Ivany1 E, Sarusi2 A, Csik3 N, Forster1 T, Curtis4 MJ, Farkas1 A
1Second Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary
2Department of Pharmacology and Pharmacotherapy, Faculty of Mechanical Engineering and Automation, University of Szeged, Szeged, Hungary
3Department of Electrical Engineering and Cybernetics, Kecskemt College, Kecskemt, Hungary
4King's College, London, UK
Introduction:
It is not well known how Class I antiarrhythmics exert their proarrhythmic activity. In our previous study Class IA (quinidine), IB (lidocaine) and IC (flecainide) antiarrhythmics did not increase the incidence of phase-I ischaemic ventricular fibrillation (VF) in isolated rat hearts perfused with 5 mM K+. In the present retrospective examination we reanalysed the ECG records of the same previous study with isolated, hearts perfused with 5 mM K+, and tested for more sensitive biomarkers of proarrhythmic risk. Proarrhythmic drugs that induce torsades de pointes (e.g. dofetilide) increase electrical instability. We examined whether quinidine, lidocaine and flecainide increased the electrical instability of the myocardium.
Methods:
Isolated, Langendorff perfused rat hearts were treated with one concentration of quinidine, lidocaine and flecainide, representing the peak unbound plasma concentration at "therapeutic" dosage in man. The hearts were subjected to regional ischaemia for 30 minutes. The Krebs' solution contained 5 mM K+ to allow a low incidence of VF in control hearts to leave room for detecting proarrhythmic effects of the studied drugs. The ECG was recorded via a ventricular needle electrode. Electrical instability of the myocardium was quantified by determining the 'absolute' beat-to-beat variability and instability (ABVI) parameters of the ECG intervals. ABVI parameters of the ECG intervals were determined at preset times irrespective of whether or not hearts were in stable sinus rhythm.
Results:
None of the applied drugs increased ABVI parameters of the ECG intervals. However, each drug decreased ABVI parameters: quinidine, lidocaine and flecainide significantly reduced 22, 4 and 36 ABVI parameters, respectively, out of the measured 50 ABVI parameters of the ECG intervals. Conclusions: Quinidine, lidocaine and flecainide reduced ABVI parameters of the ECG intervals in acute ischaemia in Langendorff perfused rat hearts. Thus, our results suggest that the mechanism of any proarrhythmia caused by quinidine, lidocaine and flecainde in acute ischaemia does not involve an elevation of the electrical instability of the myocardium.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 205, Supplement 690 :P18