title: KATP channel opening accelerates and stabilizes rotors in a swine heart model of ventricular fibrillation.
abstract: OBJECTIVE
  The mechanisms underlying ventricular fibrillation (VF) are still disputed. Recent studies have highlighted the role of KATP-channels. We hypothesized that, under certain conditions, VF can be driven by stable and epicardially detectable rotors in large hearts. To test our hypothesis, we used a swine model of accelerated VF by opening KATP-channels with cromakalim.
  
  
  RESULTS
  Optical mapping, spectral analysis, and phase singularity tracking were performed in eight perfused swine hearts during VF. Pseudo-bipolar electrograms were computed. KATP-channel opening almost doubled the maximum dominant frequency (14.3 ± 2.2 vs. 26.5 ± 2.8 Hz, P < 0.001) and increased the maximum regularity index (0.82 ± 0.05 vs. 0.94 ± 0.04, P < 0.001), the density of rotors (2.0 ± 1.4 vs. 16.0 ± 7.0 rotors/cm²×s, P < 0.001), and their maximum lifespans (medians: 368 vs. ≥3410 ms, P < 0.001). Persistent rotors (≥1 movie = 3410 ms) were found in all hearts after cromakalim (mostly coinciding with the fastest and highest organized areas), but they were not epicardially visible at baseline VF. A 'beat phenomenon' ruled by inter-domain frequency gradients was observed in all hearts after cromakalim. Acceleration of VF did not reveal any significant regional preponderance. Complex fractionated electrograms were not found in areas near persistent rotors.
  
  
  CONCLUSIONS
  Upon KATP-channel opening, VF consisted of rapid and highly organized domains mainly due to stationary rotors, surrounded by poorly organized areas. A 'beat phenomenon' due to the quasi-periodic onset of drifting rotors was observed. These findings demonstrate the feasibility of a VF driven by stable rotors in hearts whose size is similar to the human heart. Our model also showed that complex fractionation does not seem to localize stationary rotors.
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CP 28040, Madrid, Spain. jgarciaqui.hcsc@salud.madrid.org
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Quintanilla
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
authors.forename: Tamara
authors.initials: T
authors.lastname: Archondo
authors.forename: Ashley
authors.initials: A
authors.lastname: Chin
authors.forename: Nicasio
authors.initials: N
authors.lastname: Pérez-Castellano
authors.forename: Elena
authors.initials: E
authors.lastname: Usandizaga
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: García-Torrent
authors.forename: Roberto
authors.initials: R
authors.lastname: Molina-Morúa
authors.forename: Pablo
authors.initials: P
authors.lastname: González
authors.forename: Cruz
authors.initials: C
authors.lastname: Rodríguez-Bobada
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.forename: Julián
authors.initials: J
authors.lastname: Pérez-Villacastín
mesh_terms: D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D006801:Humans; D066298:In Vitro Techniques; D054086:KATP Channels / Q000819:agonists / Q000378:metabolism*; D008955:Models, Cardiovascular; D034421:Sus scrofa; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D054086:KATP Channels; D019806:Cromakalim
keywords: KATP; Optical mapping; Rotors; Ventricular fibrillation