Bradykinin B2 receptor antagonism with LF 18-1505T reduces brain edema and improves neurological outcome after closed head trauma in rats.
BACKGROUND
We evaluated the effect of LF 18-1505T, a novel nonpeptide bradykinin type-2 receptor antagonist, on brain edema and neurologic severity score (NSS) after closed head trauma (CHT).


METHODS
There were 132 rats anesthetized and assigned for sham or CHT; infusion of saline or LF 18-1505T (0.3, 1, 3, 10, or 30 microg x kg x min); and determination of neurologic outcome (brain water content and NSS) or physiologic variables (blood pressure, glucose concentration, etc.).


RESULTS
Post-CHT brain water content was less with LF 18-1505T doses of 3 and 10 microg x kg x min (80.1 +/- 3.8 through 81.6 +/- 2.6%, mean +/- SD) than in the untreated group (84.6 +/- 1.9%, p < 0.01). Post-CHT NSS improved with doses of 3, 10, and 30 microg x kg x min (median, 7; range, 0-12 through median, 10; range, 8-18) as compared with that in the untreated group (median, 17; range, 14-23; p < 0.05). LF 18-1505T with or without CHT did not significantly alter physiologic variables.


CONCLUSIONS
LF 18-1505T decreased brain edema and improved neurologic status after CTH in rats without significantly altering physiologic values.
Ivashkova
Yulia
Y
Division of Anesthesiology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Svetnitsky
Albert
A
Mayzler
Olga
O
Pruneau
Didier
D
Benifla
Mony
M
Fuxman
Yulia
Y
Cohen
Avi
A
Artru
Alan A
AA
Shapira
Yoram
Y
D000818:Animals; D065094:Bradykinin B2 Receptor Antagonists; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D016489:Head Injuries, Closed / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D065094:Bradykinin B2 Receptor Antagonists