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Ranolazine depresses conduction of rapid atrial depolarizations in a beating rabbit heart model

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Purpose

Previous clinical studies have shown that ranolazine (RAN) added to amiodarone (AMIO) might accelerate the termination of recent-onset atrial fibrillation. This study was undertaken to delineate possible mechanisms that contribute to the enhancement of the antiarrhythmic efficacy of RAN-AMIO coadministration.

Methods

Ten rabbits were anesthetized and two monophasic action potential (MAP) catheters were sequentially inserted into the right atrium. One MAP electrode was used to pace and record; the other electrode was used only for recording MAP from an adjacent atrial region. Intraatrial conduction time (IACT), 2:1 intraatrial conduction block (IACB), and atrial post-repolarization refractoriness (aPRR) were consecutively determined by high-rate atrial burst pacing and programmed stimulation, respectively. All parameters were evaluated during baseline and following AMIO (3 mg/kg iv) or AMIO+RAN (2.4 mg/kg iv bolus +0.134 mg/kg/min maintenance infusion).

Results

The IACT remained unchanged post AMIO compared with baseline (37.6 ± 3.8 vs 36.4 ± 2.4 ms), whereas the addition of RAN to AMIO significantly prolonged IACT (50.4 ± 3.6 ms, p < .001). The pacing cycle length producing 2:1 IACB was 101.2 ± 21.7 ms at baseline , 117.5 ± 15 ms after AMIO (p = 0.265), and 150 ± 14 ms after AMIO+RAN (p < .001). Baseline aPRR was longer following AMIO treatment (35 ± 5 vs 50 ± 9 ms, p < .01) but remarkably prolonged with RAN supplementation (105 ± 11 ms, p < .001).

Conclusions

RAN significantly prolonged the propagation time of rapid atrial depolarizations and potentiated the AMIO-induced moderate increases in aPRR. These mechanisms possibly contribute to the earlier termination of atrial fibrillation when RAN is co-administered with AMIO.

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Acknowledgments

We thank I. Makantasis for technical assistance during the experiments, and Dr Vet. Z. Arsenopoulou for her guidance regarding health status and anesthesia procedures of the animals.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, University of Thessaly, Larissa, Greece

    I. Aidonidis, R. Stamatiou, A. Hatziefthimiou & P-A. Molyvdas

  2. Department of Cardiac & Thoracic Surgery, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Larissa, Greece

    V. Simopoulos & S. Stravela

  3. Department of Sport Sciences at Serres, Aristotle University of Thessaloniki, Thessaloniki, Greece

    K. Dipla

Authors
  1. I. Aidonidis
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  2. V. Simopoulos
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  3. S. Stravela
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  4. K. Dipla
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  5. R. Stamatiou
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  6. A. Hatziefthimiou
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  7. P-A. Molyvdas
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Contributions

AI performed the conception, design, experimental preparation, and electrophysiologic data measurement. SV, SS, and SR performed the experimental preparation and data collection. DK, XA, and MP-A performed the statistical data analysis and English editorial of the manuscript.

Corresponding author

Correspondence to I. Aidonidis.

Ethics declarations

All experimental protocol procedures were approved by the Institutional Animal Care Committee. The study was conducted in accordance with the guidelines of the European Council on Animal Care.

Conflict of interests

The authors declare that they have no conflict of interests.

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Aidonidis, I., Simopoulos, V., Stravela, S. et al. Ranolazine depresses conduction of rapid atrial depolarizations in a beating rabbit heart model. J Interv Card Electrophysiol 62, 153–159 (2021). https://doi.org/10.1007/s10840-020-00865-0

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  • DOI: https://doi.org/10.1007/s10840-020-00865-0

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