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). CONCLUSION 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.