title: Halothane selectively inhibits bradykinin-induced synovial plasma extravasation.
abstract: BACKGROUND
  In vitro studies demonstrate that halothane, but not isoflurane, inhibits bradykinin-induced calcium currents and prostacyclin release in cultured endothelial cells. Because bradykinin is an important endogenous mediator of inflammation, we assessed the effects of halothane, isoflurane, and pentobarbital on plasma extravasation, a component of tissue inflammation induced by bradykinin, in rats.
  
  
  METHODS
  We anesthetized 23 rats with halothane (0.8 or 1.3 minimum alveolar concentration [MAC]), isoflurane (1.3 MAC), or pentobarbital (total of 85 mg/kg intraperitoneally). Their tracheas were intubated and their lungs mechanically ventilated. After intravenous administration of Evans blue dye, we perfused normal saline followed by bradykinin or platelet-activating factor, another inflammatory mediator, intraarticularly via needles placed in the knee joint. We collected perfusate and estimated extravasation by measuring dye in the perfusate using spectrophotometry.
  
  
  RESULTS
  Bradykinin increased plasma extravasation eight- to ninefold above baseline in both pentobarbital- and isoflurane-anesthetized rats. In contrast, bradykinin-induced plasma extravasation at 0.8 MAC and 1.3 MAC of halothane was approximately 40% (P < 0.01) and 15% (P < 0.001), respectively, of that in pentobarbital- and isoflurane-anesthetized rats. Baseline plasma extravasation was lower in rats anesthetized with either concentration of halothane compared with pentobarbital or isoflurane (all P < 0.001). Platelet-activating factor-induced plasma extravasation was similar for all anesthetics.
  
  
  CONCLUSIONS
  Halothane, but not isoflurane or pentobarbital, inhibits both baseline and bradykinin-induced peripheral plasma extravasation, demonstrating that volatile anesthetics differentially modulate this important component of inflammation.
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94143-0468, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Pierce
authors.forename: B S
authors.initials: BS
authors.lastname: King
authors.forename: I J
authors.initials: IJ
authors.lastname: Rampil
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D010972:Platelet Activating Factor; D001920:Bradykinin; D006221:Halothane