title: LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, improves neurologic outcome but not brain tissue prostaglandin E2 release in a rat model of closed head trauma combined with ethanol intoxication.
abstract: BACKGROUND
  LF 16-0687 Ms previously was reported to improve Neurological Severity Score (NSS) and decrease cerebral edema and prostaglandin E(2) (PGE(2)) release after closed head trauma (CHT) in rats. Here, we examined whether these beneficial effects of LF 16-0687 Ms are altered when CHT is accompanied by acute ethanol administration.
  
  
  METHODS
  Six groups of rats (n = 8 per group) were examined during combination of the following experimental conditions: CHT versus sham operation, LF 16-0687 Ms 3 mg/kg subcutaneously versus saline, and ethanol 2 g/kg versus saline.
  
  
  RESULTS
  After CHT, brain water content decreased and NSS improved with ethanol + LF 16-0687 Ms as compared with values after saline or ethanol. PGE(2) release decreased with ethanol (147 +/- 59 pg/mg tissue) but not with ethanol + LF 16-0687 Ms (286 +/- 194 pg/mg tissue).
  
  
  CONCLUSIONS
  Ethanol does not affect the improvement of NSS and the decrease of cerebral edema seen with LF 16-0687 Ms after CHT, but does reverse the ability of LF 16-0687 Ms to minimize the increase of PGE(2) release. In intoxicated patients, bradykinin antagonist therapy may improve post-CHT outcome without altering PGE(2) release.
authors.affiliation: Division of Anesthesiology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Asa
authors.forename: Yulia
authors.initials: Y
authors.lastname: Ivashkova
authors.forename: Alan A
authors.initials: AA
authors.lastname: Artru
authors.forename: Matityahu
authors.initials: M
authors.lastname: Lifshitz
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gavrilov
authors.forename: Abed N
authors.initials: AN
authors.lastname: Azab
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kapuler
authors.forename: Andrei
authors.initials: A
authors.lastname: Alouchin
authors.forename: Maxim
authors.initials: M
authors.lastname: Rachinsky
authors.forename: Didier
authors.initials: D
authors.lastname: Pruneau
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shapira
authors.forename: Jacob
authors.initials: J
authors.lastname: Kaplanski
mesh_terms: D000435:Alcoholic Intoxication / Q000150:complications*; D000818:Animals; D065168:Bradykinin Receptor Antagonists; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001927:Brain Diseases / Q000145:classification / Q000517:prevention & control*; D001929:Brain Edema / Q000517:prevention & control*; D015232:Dinoprostone / Q000096:biosynthesis*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology; D016489:Head Injuries, Closed / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009483:Neuropsychological Tests; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index
chemical_list: D065168:Bradykinin Receptor Antagonists; C403051:LF 16-0687; D011804:Quinolines; D000431:Ethanol; D015232:Dinoprostone