title: Isoflurane does not mimic ischaemic preconditioning in decreasing hydroxyl radical production in the rabbit.
abstract: BACKGROUND
  Reactive oxygen species are an important mediator in isoflurane-induced myocardial preconditioning. However, hydroxyl radicals are also released during reperfusion after regional ischaemia. The purpose of the present study was to test whether ischaemic preconditioning and isoflurane would influence the production of hydroxyl radicals during reperfusion.
  
  
  METHODS
  After i.v. administration of salicylate 100 mg kg(-1) and a 30 min stabilization period, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia and 2 h of reperfusion. Ischaemic preconditioning was elicited by 5 min ischaemia followed by 10 min reperfusion (before the 40 min ischaemia). In another group, isoflurane (2.1%) was administered for 30 min, followed by 15 min washout, before the long ischaemia. Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. We quantified the level of OH-mediated conversion of salicylate to its dihydrobenzoate derivatives (2,3- and 2,5-DHBAs). Normalized values of the DHBAs (ng DHBA per mg salicylate) were calculated.
  
  
  RESULTS
  Mean (se) infarct size was 57 (6)% of the risk area in the untreated controls. This was significantly smaller in the ischaemic preconditioning and isoflurane groups: 22 (5) and 23 (6)% respectively. At 10 min of reperfusion, ischaemic preconditioning limited the mean increase in 2,3-DHBA to 24% from baseline, compared with 81% in control and 74% in the isoflurane group. Normalized 2,5-DHBA was maximally increased by 75% in the untreated group, 4 min after reperfusion. Ischaemic preconditioning significantly inhibited this increase (24% increase from baseline, P<0.01). However, the increase observed in the isoflurane group was not different from control (71%).
  
  
  CONCLUSIONS
  As already known, ischaemic preconditioning and isoflurane markedly reduced infarct size. However, only ischaemic preconditioning decreased postischaemic production of hydroxyl radicals. These different effects suggest different protective mechanisms at the cellular level.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. gozaly@md.huji.ac.il
authors.forename: Y
authors.initials: Y
authors.lastname: Gozal
authors.forename: J
authors.initials: J
authors.lastname: Raphael
authors.forename: J
authors.initials: J
authors.lastname: Rivo
authors.forename: E
authors.initials: E
authors.lastname: Berenshtein
authors.forename: M
authors.initials: M
authors.lastname: Chevion
authors.forename: B
authors.initials: B
authors.lastname: Drenger
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D005841:Gentisates; D006439:Hemodynamics / Q000187:drug effects; D062385:Hydroxybenzoates / Q000097:blood; D017665:Hydroxyl Radical / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D011817:Rabbits
chemical_list: D018685:Anesthetics, Inhalation; D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D007530:Isoflurane; C010925:2,5-dihydroxybenzoic acid