Ion channels and ElectrophysiologyP98The possible proarrhythmic effects of diclofenac

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Abstract

Introduction

Sudden cardiac death among athletes is very rare but 2-4 times more frequent than in the age- matched control population. Non-steroidal anti-inflammatory drugs (NSAIDs) like diclofenac are widely used in the treatment of sports injuries, however, their effects on the cardiac electrophysiological parameters are not properly understood. It is possible that the NSAID diclofenac might cause ventricular repolarisation abnormalities contributing to the increased arrhythmic risk of young athletes. Therefore the aim of our study was to characterize the cellular electrophysiological effect of diclofenac on dog right ventricular preparations.

Methods

Action potential measurements were carried out by applying the standard intracellular microelectrode technique in right ventricular papillary muscle preparations isolated from mongrel dogs of either sex weighing 12–20 kg. Ionic currents were recorded using the whole-cell configuration of the patch-clamp technique in single ventricular myocytes isolated from dog hearts. The experimental temperature was 37°C.

Results

Diclofenac slightly lengthened the action potential duration at 90% repolarisation (APD90) without affecting the maximum upstroke of AP (Vmax). In the presence of 100 nM IKr blocker dofetilide, 20 μM diclofenac caused significant additional APD90 lengthening in a reverse frequency dependent manner. The drug induced a marked further increasing relative to the APD values measured after the administration of 100 nM Dofetilide and 30 μM BaCl2, ie. the APD lengthening effect of diclofenac was significantly augmented in preparations where the “repolarisation reserve” was attenuated by previous application of dofetilide and BaCl2. In some experiments early afterdepolarisations (EADs) developed in this setting. During the experiments transmembran ionic currents were also measured. In dog ventricular myocytes the amplitude of IKr was concentration dependently decreased by diclofenac. IKs was also depressed by 30 μM diclofenac.

Conclusions

At therapeutic concentration diclofenac alone does not influence ventricular repolarisation significantly. However, in the case of impaired "repolarisation reserve" such as organic heart disease or in athlete's heart, diclofenac may enhance the arrhythmic risk and sudden cardiac death by increasing the APD and developing EADs.

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