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.
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.
Asa
Ilia
I
Division of Anesthesiology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Ivashkova
Yulia
Y
Artru
Alan A
AA
Lifshitz
Matityahu
M
Gavrilov
Vladimir
V
Azab
Abed N
AN
Kapuler
Vladimir
V
Alouchin
Andrei
A
Rachinsky
Maxim
M
Pruneau
Didier
D
Shapira
Yoram
Y
Kaplanski
Jacob
J
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
D065168:Bradykinin Receptor Antagonists; C403051:LF 16-0687; D011804:Quinolines; D000431:Ethanol; D015232:Dinoprostone