caa a22 4500 606158499 CHVBK 20210128100619.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10557-015-6587-4 doi (NATIONALLICENCE)springer-10.1007/s10557-015-6587-4 Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts [Elektronische Daten] [Francisco Chorro, Irene del Canto, Laia Brines, Luis Such-Miquel, Conrado Calvo, Carlos Soler, Germán Parra, Manuel Zarzoso, Isabel Trapero, Álvaro Tormos, Antonio Alberola, Luis Such] Purpose: Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na + current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch. Methods: The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (n = 9) or during perfusion of the late Na + current blocker ranolazine 5μM (n = 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch. Results: Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0 vs 40.4%) (control: baseline =13.6 ± 2.6Hz, stretch = 19.1 ± 3.1Hz, p < 0.0001; ranolazine: baseline = 11.4 ± 1.8Hz, stretch =14.0 ± 2.4Hz, p < 0.05 vs baseline, p < 0.001 vs control). During stretch, ventricular fibrillation was less complex in the ranolazine than in the control series, as evaluated by the lesser percentage of complex maps and the greater spectral concentration of ventricular fibrillation. These changes were associated to an increase in the fifth percentile of VV intervals during ventricular fibrillation (50 ± 8 vs 38 ± 5ms, p < 0.01) and in the wavelength of the activation (2.4 ± 0.3 vs 1.9 ± 0.2cm, p < 0.001) under ranolazine. Conclusions: The late inward Na + current inhibitor ranolazine attenuates the electrophysiological effects responsible for the acceleration and increase in complexity of ventricular fibrillation produced by myocardial stretch. Springer Science+Business Media New York, 2015 Mechanoelectric feedback nationallicence Myocardial stretch nationallicence Ranolazine nationallicence Ventricular fibrillation nationallicence Mapping nationallicence Chorro Francisco Service of Cardiology, Valencia University Clinic Hospital, INCLIVA, Valencia, Spain aut del Canto Irene Department of Medicine, Valencia University - Estudi General, Valencia, Spain aut Brines Laia Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut Such-Miquel Luis Department of Physiotherapy, Valencia University - Estudi General, Valencia, Spain aut Calvo Conrado Department of Electronics, Valencia Polytechnic University, Valencia, Spain aut Soler Carlos Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut Parra Germán Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut Zarzoso Manuel Department of Physiotherapy, Valencia University - Estudi General, Valencia, Spain aut Trapero Isabel Department of Infirmary, Valencia University - Estudi General, Valencia, Spain aut Tormos Álvaro Department of Electronics, Valencia Polytechnic University, Valencia, Spain aut Alberola Antonio Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut Such Luis Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 231-241 0920-3206 29:3<231 2015 29 10557 https://doi.org/10.1007/s10557-015-6587-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-015-6587-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chorro Francisco Service of Cardiology, Valencia University Clinic Hospital, INCLIVA, Valencia, Spain aut NATIONALLICENCE 700 1- del Canto Irene Department of Medicine, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Brines Laia Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Such-Miquel Luis Department of Physiotherapy, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Calvo Conrado Department of Electronics, Valencia Polytechnic University, Valencia, Spain aut NATIONALLICENCE 700 1- Soler Carlos Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Parra Germán Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Zarzoso Manuel Department of Physiotherapy, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Trapero Isabel Department of Infirmary, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Tormos Álvaro Department of Electronics, Valencia Polytechnic University, Valencia, Spain aut NATIONALLICENCE 700 1- Alberola Antonio Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 700 1- Such Luis Department of Physiology, Valencia University - Estudi General, Valencia, Spain aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 231-241 0920-3206 29:3<231 2015 29 10557