Ranolazine depresses conduction of rapid atrial depolarizations in a beating rabbit heart model
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Ranolazine depresses conduction of rapid atrial depolarizations in a beating rabbit heart model I. Aidonidis 1
&
V. Simopoulos 2 & S. Stravela 2 & K. Dipla 3 & R. Stamatiou 1 & A. Hatziefthimiou 1 & P-A. Molyvdas 1
Received: 9 June 2020 / Accepted: 4 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Rabbit heart . Right atrium . Monophasic action potentials . Atrial conduction . Amiodarone . Ranolazine
1 Introduction The clinical impact of intravenously administered ranolazine (RAN) as a monotherapy for terminating certain forms of atrial fibrillation (AF) has not been adequately examined due * I. Aidonidis [email protected] 1
Department of Physiology, Faculty of Medicine, University of Thessaly, Larissa, Greece
2
Department of Cardiac & Thoracic Surgery, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Larissa, Greece
3
Department of Sport Sciences at Serres, Aristotle University of Thessaloniki, Thessaloniki, Greece
to its limited parenteral application in in-hospital patients. Nonetheless, clinical studies have shown that oral RAN when co-administered with intravenous AMIO significantly shortened the time to conversion of recent-onset AF to sinus rhythm [1–3]. The exact mechanisms through which RA
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