The importance of kinin antagonist treatment timing in closed head trauma

Background., Giving LF 16-0687 Ms (a bradykinin B2 receptor antagonist) I h our after closed head trauma (CRT) previously was reported to decrease brai n 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 CRT. Methods: To examine the latter possibility we studied a surrogate condition for the earliest possible administration of LF 16-0687 Ms after CRT, 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 a fter CRT in comparison to that with CRT + saline (82.9 +/- 1.3% and 8 +/- 4 ). Conclusion Similarity of the present results to those previously reported i ndicates that the benefit of giving LF 16-0687 Ms 1 hour after CRT appears to represent the maximal benefit afforded by this drug.