title: Nitric oxide has no obligatory role in isoflurane late preconditioning against myocardial stunning.
abstract: OBJECTIVE
  Isoflurane has been demonstrated to produce late preconditioning against myocardial stunning. We tested the hypothesis that this effect is dependent upon an increased production of nitric oxide.
  
  
  METHODS
  Studies were performed in 18 conscious dogs, chronically instrumented to measure coronary blood flow and myocardial wall thickening (WT). In Group 1 (control; n=7), a 10-min coronary occlusion was produced followed by reperfusion; WT was monitored until full recovery. In Group 2 (n=6), the same occlusion-reperfusion protocol was performed 24h after inhalation of 1 MAC isoflurane (1.4% in O(2)) for 60 min. In Group 3 (n=5), the late anti-stunning effect of isoflurane was evaluated following non-selective inhibition of NOS with N-nitro-l-arginine (l-NA, 30 mg/kg on 3 days beginning 1 day prior to isoflurane). Expression of eNOS and iNOS protein was measured by Western blotting.
  
  
  RESULTS
  Two to 3h of reperfusion was required for recovery of WT following isoflurane (Group 2). In contrast, without isoflurane (Group 1), WT remained markedly reduced (30% below baseline) at this time point and required more than 6h of reperfusion for recovery. Treatment with l-NA (Group 3) did not alter time-course of recovery of WT following isoflurane. Isoflurane caused an increased expression of eNOS, but not of iNOS.
  
  
  CONCLUSIONS
  Isoflurane produced late preconditioning against myocardial stunning. Although this effect was associated with an up-regulation of eNOS, its persistence following l-NA suggested that an increased production of nitric oxide did not play an obligatory role.
authors.affiliation: Section of Cardiology, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USA.
authors.forename: Song-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Gautam
authors.initials: G
authors.lastname: Malik
authors.forename: Maged M
authors.initials: MM
authors.lastname: Saad
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Yoon
authors.forename: Joaquin B
authors.initials: JB
authors.lastname: Gonzalez
authors.forename: George J
authors.initials: GJ
authors.lastname: Crystal
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D015153:Blotting, Western; D004285:Dogs; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000494:pharmacology*; D017682:Myocardial Stunning / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D015424:Reperfusion / Q000379:methods
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II