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The anti-influenza drug oseltamivir reduces atrial fibrillation in an experimental whole-heart model

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Abstract

Recent experimental studies suggested direct effects of the anti-influenza drug oseltamivir on cardiac electrophysiology. We therefore aimed at analyzing potential antiarrhythmic effects of oseltamivir on atrial fibrillation (AF) in an experimental whole-heart model. Twelve rabbit hearts were isolated and Langendorff perfused. Thereafter, hearts were paced at cycle lengths of 350, 250, and 200 ms in the atrium. A standardized protocol employing atrial burst pacing induced AF in 4 of 12 hearts under baseline conditions (33%, 11 episodes). Subsequently, a combination of acetylcholine (1 μM) and isoproterenol (1 μM) was administered to increase AF occurrence. Two monophasic action potential recordings on the left and two on the right atrial epicardium displayed a decrease of atrial action potential duration (aAPD, −38 ms, p < 0.01) and atrial effective refractory period (aERP; −20 ms, p < 0.05). Under the influence of acetylcholine/isoproterenol AF was inducible in 8 of 12 hearts (66%; 69 episodes). Additional infusion of oseltamivir (100 μM) resulted in a significant increase of both aAPD (+ 29 ms, p < 0.05) and aERP (+ 40 ms, p < 0.01) leading to an increase of atrial post-repolarization refractoriness (aPRR). Under the influence of oseltamivir only 3 of 12 hearts (25%, 8 episodes) remained inducible. In six additional hearts oseltamivir (50 μM and 100 μM) did not significantly alter ventricular APD, QRS duration and QT interval but induced a significant increase of ventricular ERP. In the present experimental study, acute infusion of the anti-influenza drug oseltamivir reduced atrial fibrillation. The antiarrhythmic effect can be explained by a significant increase in aERP and aPRR. These results suggest an antiarrhythmic potential of oseltamivir in atrial arrhythmias.

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Acknowledgments

This study was supported by the German Cardiac Society (to G.F.) and the Dr. Peter Osypka Foundation.

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Authors and Affiliations

  1. Division of Electrophysiology, Department of Cardiovascular Medicine, University Hospital of Münster, Münster, Germany

    Gerrit Frommeyer, André Mittelstedt, Julian Wolfes, Christian Ellermann, Simon Kochhäuser, Patrick Leitz, Dirk G. Dechering & Lars Eckardt

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  1. Gerrit Frommeyer
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  2. André Mittelstedt
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  3. Julian Wolfes
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  4. Christian Ellermann
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  5. Simon Kochhäuser
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  6. Patrick Leitz
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  7. Dirk G. Dechering
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  8. Lars Eckardt
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Correspondence to Gerrit Frommeyer.

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Frommeyer, G., Mittelstedt, A., Wolfes, J. et al. The anti-influenza drug oseltamivir reduces atrial fibrillation in an experimental whole-heart model. Naunyn-Schmiedeberg's Arch Pharmacol 390, 1155–1161 (2017). https://doi.org/10.1007/s00210-017-1415-y

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  • DOI: https://doi.org/10.1007/s00210-017-1415-y

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