The importance of kinin antagonist treatment timing in closed head trauma.
BACKGROUND
Giving LF 16-0687 Ms (a bradykinin B2 receptor antagonist) 1 hour after closed head trauma (CHT) previously was reported to decrease brain edema at 24 hours and improve neurologic severity score (NSS) at 7 days. It is not certain whether a greater benefit could be achieved by treatment sooner after CHT.


METHODS
To examine the latter possibility we studied a surrogate condition for the earliest possible administration of LF 16-0687 Ms after CHT, e.g., we examined brain edema and NSS when LF 16-0687 Ms was given 15 min before CHT in rats.


RESULTS
LF 16-0687 Ms decreased brain water content (80.0 +/- 1.4%, mean +/- SD) at 24 hours and improved NSS (2 +/- 3, median +/- range) at 7 days after CHT in comparison to that with CHT + saline (82.9 +/- 1.3% and 8 +/- 4).


CONCLUSIONS
Similarity of the present results to those previously reported indicates that the benefit of giving LF 16-0687 Ms 1 hour after CHT appears to represent the maximal benefit afforded by this drug.
Rachinsky
M
M
Division of Anesthesiology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Pruneau
D
D
Artru
A A
AA
Kapuler
V
V
Alonchin
A
A
Smolanezki
Y
Y
Shapira
Y
Y
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D065168:Bradykinin Receptor Antagonists; D001929:Brain Edema / Q000188:drug therapy* / Q000503:physiopathology; D016489:Head Injuries, Closed / Q000188:drug therapy* / Q000503:physiopathology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D018709:Statistics, Nonparametric; D013997:Time Factors
D065168:Bradykinin Receptor Antagonists; C403051:LF 16-0687; D011804:Quinolines; D043782:Receptor, Bradykinin B2