title: Sevoflurane reduces leukocyte and platelet adhesion after ischemia-reperfusion by protecting the endothelial glycocalyx.
abstract: BACKGROUND
  Adhesion of polymorphonuclear neutrophils and platelets to the vessel wall contributes to generating ischemia-reperfusion injury. Endothelial adhesion molecules are harbored within the glycocalyx, which covers every healthy vascular endothelium but is deteriorated by ischemia-reperfusion. Pretreating the heart with volatile anesthetics reduces myocardial infarct size and protects against ischemia-reperfusion injury. The authors analyzed a possible protective effect of sevoflurane on the glycocalyx and implications for postischemic cell adhesion.
  
  
  METHODS
  Isolated guinea pig hearts were perfused with crystalloid buffer and subjected to 20 min of global warm ischemia and 10 min of reperfusion. An intracoronary bolus of 3 x 10(6) polymorphonuclear neutrophilic leukocytes or 1 x 10(9) platelets of human origin was applied after reperfusion, either with or without pretreating with 0.5 or 1 minimal alveolar concentration sevoflurane. The number of sequestered cells was calculated from the difference between coronary input and output. Coronary effluent was collected throughout reperfusion to measure shedding of the glycocalyx.
  
  
  RESULTS
  Ischemia-reperfusion induced a significant increase in median (interquartile range) adhesion versus control nonischemic hearts of both leukocytes (38.9 (36.3-42.9) vs. 14.5 (13.1-16.0)%) and platelets (25.0 (22.5-27.1) vs. 9.4 (8.4-10.7)%). Shedding was evidenced by eightfold increases in washout of syndecan-1 and heparan sulfate versus basal. Sevoflurane reduced cell adhesion to near basal at 1 minimal alveolar concentration (leukocytes: 21.2% (19.2-23.9%), platelets: 11.5% (10.4-12.0%). Shedding measurements and electron microscopy demonstrated that sevoflurane-treated hearts retained much of their 200 nm-thick glycocalyx.
  
  
  CONCLUSIONS
  Sevoflurane reduces glycocalyx shedding in the postischemic coronary bed, maintaining the natural cover for endothelial adhesion molecules and, thus, reducing cell adhesion. This may explain beneficial outcomes linked to clinical use of volatile anesthetics after ischemia-reperfusion.
authors.affiliation: Clinic of Anesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany. daniel.chappell@med.uni-muenchen.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappell
authors.forename: Bernhard
authors.initials: B
authors.lastname: Heindl
authors.forename: Matthias
authors.initials: M
authors.lastname: Jacob
authors.forename: Thorsten
authors.initials: T
authors.lastname: Annecke
authors.forename: Congcong
authors.initials: C
authors.lastname: Chen
authors.forename: Markus
authors.initials: M
authors.lastname: Rehm
authors.forename: Peter
authors.initials: P
authors.lastname: Conzen
authors.forename: Bernhard F
authors.initials: BF
authors.lastname: Becker
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D004487:Edema / Q000473:pathology; D004727:Endothelium / Q000187:drug effects* / Q000648:ultrastructure; D005434:Flow Cytometry; D019276:Glycocalyx / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D006168:Guinea Pigs; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008738:Methyl Ethers / Q000494:pharmacology*; D008854:Microscopy, Electron; D009504:Neutrophils / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D015427:Reperfusion Injury / Q000473:pathology*; D000077149:Sevoflurane; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D006497:Heparan Sulfate; D008738:Methyl Ethers; D000077149:Sevoflurane; D053668:Syndecan-1