title: ATP-sensitive potassium channels do not have a main role in mediating late preconditioning protection against arrhythmias and stunning in conscious sheep.
abstract: OBJECTIVE
  Although late preconditioning protects against stunning following several short periods of ischemia-reperfusion, it is not clear if it confers protection against stunning and malignant arrhythmias after a sustained reversible ischemia, and whether KATP channels are involved as triggers and/or end effectors of the protective mechanism. The purpose of this work was thus to test these issues in conscious sheep.
  
  
  METHODS
  Five groups were considered: CONT (control): the animals were submitted to 12 min ischemia followed by 2 h reperfusion; SWOP (late preconditioning): on the first day, the animals were preconditioned with 6 periods of 5 min ischemia 5 min reperfusion and 24 h later they were submitted to 12 min ischemia followed by 2 h reperfusion; GLIB: same as CONT with the KATP channel inhibitor glibenclamide (0.4 mg/kg) infused 30 min prior to the 12 min ischemia; SWOPG2: same as SWOP with glibenclamide before the 12 min ischemia; SWOPG1: same as SWOP with glibenclamide prior to the preconditioning stimulus.
  
  
  RESULTS
  Percent reperfusion recovery of wall thickening fraction (% WTh) showed late preconditioning protection against stunning throughout reperfusion (SWOP vs CONT, p < 0.01). Arrhythmia severity index (ASI) also demonstrated that late preconditioning protects against malignant arrhythmias at the onset of reperfusion (CONT: 4.87 +/- 1.62 vs SWOP: 1.39 +/- 0.93, p < 0.01). Glibenclamide was unable to prevent preconditioning, both against stunning and arrhythmia incidence, when administered either before the preconditioning stimulus (SWOPG1 vs CONT, p < 0.01) or before the sustained ischemia (SWOPG2 vs GLI, p < 0.01).
  
  
  CONCLUSIONS
  Results indicate that late preconditioning protects against stunning and arrhythmias following a reversible, sustained ischemia in conscious sheep and that KATP channel participation is negligible as triggers and end effectors of both types of protection.
authors: Department of Physiology, Pharmacology and Biochemistry, Favaloro University, Buenos Aires, Argentinia. negroni@favaloro.edu.ar
authors: Jorge A
authors: JA
authors: Negroni
authors: Elena C
authors: EC
authors: Lascano
authors: Héctor F
authors: HF
authors: del Valle
authors: Alberto J
authors: AJ
authors: Crottogini
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D003243:Consciousness; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D017682:Myocardial Stunning / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D012756:Sheep
chemical_list: D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide