title: Role of KATP channel in electrical depression and asystole during long-duration ventricular fibrillation in ex vivo canine heart.
abstract: Long-duration ventricular fibrillation (LDVF) in the globally ischemic heart is characterized by transmurally heterogeneous decline in ventricular fibrillation rate (VFR), emergence of inexcitable regions, and eventual global asystole. Rapid loss of both local and global excitability is detrimental to successful defibrillation and resuscitation during cardiac arrest. We sought to assess the role of the ATP-sensitive potassium current (I(KATP)) in the timing and spatial pattern of electrical depression during LDVF in a structurally normal canine heart. We analyzed endo-, mid-, and epicardial unipolar electrograms and epicardial optical recordings in the left ventricle of isolated canine hearts during 10 min of LDVF in the absence (control) and presence of an I(KATP) blocker glybenclamide (60 μM). In all myocardial layers, average VFR was the same or higher in glybenclamide-treated than in control hearts. The difference increased with time of LDVF and was overall significant in all layers (P < 0.05). However, glybenclamide did not significantly affect the transmural VFR gradient. In epicardial optical recordings, glybenclamide shortened diastolic intervals, prolonged action potential duration, and decreased the percentage of inexcitable area (all differences P < 0.001). During 10 min of LDVF, asystole occurred in 55.6% of control and none of glybenclamide-treated hearts (P < 0.05). In three hearts paced after the onset of asystole, there was no response to LV epicardial or atrial pacing. In structurally normal canine hearts, I(KATP) opening during LDVF is a major factor in the onset of local and global inexcitability, whereas it has a limited role in overall deceleration of VFR and the transmural VFR gradient.
authors.affiliation: Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, 84112-5000, USA.
authors.forename: Tyson G
authors.initials: TG
authors.lastname: Taylor
authors.forename: Paul W
authors.initials: PW
authors.lastname: Venable
authors.forename: Junko
authors.initials: J
authors.lastname: Shibayama
authors.forename: Mark
authors.initials: M
authors.lastname: Warren
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Zaitsev
mesh_terms: D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006323:Heart Arrest / Q000503:physiopathology*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D054086:KATP Channels; D005905:Glyburide