title: Gender-specificity of delayed preconditioning by isoflurane in rabbits: potential role of endothelial nitric oxide synthase.
abstract: BACKGROUND
  Female gender confers cardioprotection against ischemia-reperfusion injury, in part because estrogen enhances nitric oxide production by endothelial nitric oxide synthase (eNOS). Whether ischemic preconditioning occurs in females remains controversial. Delayed myocardial preconditioning by isoflurane is mediated by eNOS in male rabbits, but whether females are similarly protected by isoflurane is unknown. We tested the hypothesis that gender-specific reductions in myocardial infarct size occur in female rabbits, but that this inherent cardioprotection abrogates further beneficial effects of isoflurane-induced delayed preconditioning.
  
  
  METHODS
  Rabbits (n = 115) underwent a 30 min coronary artery occlusion and 3 h reperfusion with or without a 2 h administration of 1.0 minimum alveolar concentration isoflurane one day before experimentation. Rabbits received saline or a nonselective, selective inducible, or selective neuronal NOS inhibitor [N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), aminoguanidine (AG, 300 mg/kg), or 7-nitroindazole (7-NI, 50 mg/kg), respectively].
  
  
  RESULTS
  Isoflurane reduced infarct size in males (mean+/- sd, 26 +/- 5% of the left ventricular area at risk) versus saline (45 +/- 2%). L-NAME, but not AG or 7-NI, abolished isoflurane-induced protection in males (41 +/- 9, 24 +/- 4 and 22 +/- 2%, respectively). Infarct size was reduced, and eNOS protein expression was greater, in female versus male rabbits. Infarct size was unchanged in female rabbits with, versus without, isoflurane pretreatment (27 +/- 9 and 27 +/- 10%, respectively). L-NAME, but not AG or 7-NI, increased infarct size with or without isoflurane pretreatment in females.
  
  
  CONCLUSIONS
  Female gender-induced reductions in infarct size are mediated by eNOS, but remote isoflurane exposure (1.0 MAC) before ischemia and reperfusion does not produce additional cardioprotection in vivo.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin and Clement J. Zablocki Veterans Affairs Medical Center, MEB-M4280, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Pascal C
authors.initials: PC
authors.lastname: Chiari
authors.forename: Dorothee
authors.initials: D
authors.lastname: Weihrauch
authors.forename: John G
authors.initials: JG
authors.lastname: Krolikowski
authors.forename: David C
authors.initials: DC
authors.lastname: Warltier
authors.forename: Judy R
authors.initials: JR
authors.lastname: Kersten
authors.forename: Phillip F
authors.initials: PF
authors.lastname: Pratt
authors.forename: Paul S
authors.initials: PS
authors.lastname: Pagel
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D011817:Rabbits; D012737:Sex Factors
chemical_list: D018685:Anesthetics, Inhalation; D006146:Guanidines; D007191:Indazoles; D007530:Isoflurane; D052250:Nitric Oxide Synthase Type III; C004479:pimagedine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester