title: Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts.
abstract: OBJECTIVE
  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 5 μM (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 ± 2.6 Hz, stretch = 19.1 ± 3.1 Hz, p < 0.0001; ranolazine: baseline =  1.4 ± 1.8 Hz, stretch =14.0 ± 2.4 Hz, 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 ± 5 ms, p <  .01) and in the wavelength of the activation (2.4 ± 0.3 vs 1.9 ± 0.2 cm, 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.
authors.affiliation: Service of Cardiology, Valencia University Clinic Hospital, INCLIVA, Valencia, Spain, Francisco.J.Chorro@uv.es.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Chorro
authors.forename: Irene
authors.initials: I
authors.lastname: del Canto
authors.forename: Laia
authors.initials: L
authors.lastname: Brines
authors.forename: Luis
authors.initials: L
authors.lastname: Such-Miquel
authors.forename: Conrado
authors.initials: C
authors.lastname: Calvo
authors.forename: Carlos
authors.initials: C
authors.lastname: Soler
authors.forename: Germán
authors.initials: G
authors.lastname: Parra
authors.forename: Manuel
authors.initials: M
authors.lastname: Zarzoso
authors.forename: Isabel
authors.initials: I
authors.lastname: Trapero
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Tormos
authors.forename: Antonio
authors.initials: A
authors.lastname: Alberola
authors.forename: Luis
authors.initials: L
authors.lastname: Such
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects*; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D066298:In Vitro Techniques; D000067268:Isolated Heart Preparation; D011817:Rabbits; D000069458:Ranolazine / Q000494:pharmacology* / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000069458:Ranolazine