title: Sevoflurane inhalation at sedative concentrations provides endothelial protection against ischemia-reperfusion injury in humans.
abstract: BACKGROUND
  Endothelial cells can be protected against cytokine-induced toxicity by volatile anesthetics. The authors tested whether inhalation of sevoflurane at subanesthetic concentrations provides protection against postocclusive endothelial dysfunction induced by ischemia-reperfusion injury of the forearm in humans.
  
  
  METHODS
  Five healthy male volunteers were enrolled in this study with crossover design. Each subject was randomly exposed to 15 min of forearm ischemia in the presence or absence of sevoflurane. Sevoflurane was inhaled at 0.5-1 vol% end-tidal concentrations from 15 min before ischemia until 5 min after the onset of reperfusion. Hyperemic reaction, an indicator of ischemic injury and endothelial function, was determined at 15 and 30 min of reperfusion using venous occlusion plethysmography. Also, markers of leukocyte activation (CD11b, CD42b) were measured by flow cytometry during reperfusion.
  
  
  RESULTS
  Fifteen minutes of forearm ischemia followed by reperfusion diminished postocclusive endothelium-dependent hyperemic reaction at 15 and 30 min of reperfusion. Peri-ischemic inhalation of sevoflurane, targeted at 0.5-1 vol% end-tidal concentrations, markedly improved postocclusive hyperemic reaction. In addition, inhalation of sevoflurane attenuated activation of leukocytes, as measured by CD11b expression, after ischemia-reperfusion injury. No changes in CD42b expression were observed after ischemia-reperfusion of the forearm.
  
  
  CONCLUSIONS
  These data suggest that human endothelium, a key component of all vital organs, is receptive to protection by sevoflurane in vivo. Peri-ischemic administration of sevoflurane mimics a combination of pharmacologic preconditioning and postconditioning and protects at even low sedative concentrations (< 1 vol%). Inhibition of leukocyte adhesion is likely to be involved in the protection.
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Switzerland.
authors.forename: Eliana
authors.initials: E
authors.lastname: Lucchinetti
authors.forename: Sandro
authors.initials: S
authors.lastname: Ambrosio
authors.forename: José
authors.initials: J
authors.lastname: Aguirre
authors.forename: Patrick
authors.initials: P
authors.lastname: Herrmann
authors.forename: Luc
authors.initials: L
authors.lastname: Härter
authors.forename: Marius
authors.initials: M
authors.lastname: Keel
authors.forename: Thomas
authors.initials: T
authors.lastname: Meier
authors.forename: Michael
authors.initials: M
authors.lastname: Zaugg
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D039481:CD11b Antigen / Q000032:analysis; D018592:Cross-Over Studies; D019610:Cytoprotection; D042783:Endothelial Cells / Q000187:drug effects*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D039481:CD11b Antigen; D008738:Methyl Ethers; D000077149:Sevoflurane