title: Modifications of mechanoelectric feedback induced by 2,3-butanedione monoxime and Blebbistatin in Langendorff-perfused rabbit hearts.
abstract: OBJECTIVE
  Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch.
  
  
  METHODS
  The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n = 9) and during the perfusion of 2,3-butanedione monoxime (15 mM) (n = 9) or Blebbistatin (10 μm) (n = 9).
  
  
  RESULTS
  In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1 ± 2.0 Hz to 19.1 ± 3.1 Hz (P < 0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4 ± 1.2 Hz; P < 0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF = 11.7 ± 2.4 Hz, 5% increment, ns vs baseline, P < 0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P < 0.01 vs. baseline, P < 0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin.
  
  
  CONCLUSIONS
  The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.
authors.affiliation: Department of Medicine, Valencia University, Estudi General, Valencia, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Brines
authors.forename: L
authors.initials: L
authors.lastname: Such-Miquel
authors.forename: D
authors.initials: D
authors.lastname: Gallego
authors.forename: I
authors.initials: I
authors.lastname: Trapero
authors.forename: I
authors.initials: I
authors.lastname: Del Canto
authors.forename: M
authors.initials: M
authors.lastname: Zarzoso
authors.forename: C
authors.initials: C
authors.lastname: Soler
authors.forename: F
authors.initials: F
authors.lastname: Pelechano
authors.forename: J
authors.initials: J
authors.lastname: Cánoves
authors.forename: A
authors.initials: A
authors.lastname: Alberola
authors.forename: L
authors.initials: L
authors.lastname: Such
authors.forename: F J
authors.initials: FJ
authors.lastname: Chorro
mesh_terms: D000818:Animals; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011817:Rabbits
chemical_list: D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; C004717:diacetylmonoxime; C472645:blebbistatin; D003931:Diacetyl