title: Role of KATP channels in the maintenance of ventricular fibrillation in cardiomyopathic human hearts.
abstract: BACKGROUND
  Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF.
  
  
  OBJECTIVE
  We addressed the hypotheses that there is regional disease-related expression of K(ATP) channels in human cardiomyopathic hearts and that K(ATP) channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness.
  
  
  RESULTS
  In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 μmol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K(ATP) subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all K(ATP) subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (ΔERP(Transmural)=ERP(Epicardium)-ERP(Endocardium)) was verified with pacing protocols. ΔERP(Transmural) in control was 5 ± 2 ms and increased to 36 ± 5 ms with ischemia. This effect was greatly attenuated by glibenclamide (ΔERP(Transmural) for glibenclamide+ischemia=4.9 ± 4 ms, P=0.019 versus control ischemia).
  
  
  CONCLUSIONS
  K(ATP) channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K(ATP) channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.
authors: University Health Network, Toronto, Ontario, Canada.
authors: Talha A
authors: TA
authors: Farid
authors: Krishnakumar
authors: K
authors: Nair
authors: Stephéne
authors: S
authors: Massé
authors: Mohammed Ali
authors: MA
authors: Azam
authors: Ange
authors: A
authors: Maguy
authors: Patrick F H
authors: PF
authors: Lai
authors: Karthikeyan
authors: K
authors: Umapathy
authors: Paul
authors: P
authors: Dorian
authors: Vijay
authors: V
authors: Chauhan
authors: András
authors: A
authors: Varró
authors: Abdul
authors: A
authors: Al-Hesayen
authors: Menashe
authors: M
authors: Waxman
authors: Stanley
authors: S
authors: Nattel
authors: Kumaraswamy
authors: K
authors: Nanthakumar
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D004699:Endocardium / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D054086:KATP Channels / Q000502:physiology*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology; D010138:Pacemaker, Artificial; D010477:Perfusion; D010496:Pericardium / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology*
chemical_list: D054086:KATP Channels; D012333:RNA, Messenger; D008012:Lidocaine; D005905:Glyburide