Neurotensin analog NT69L induces rapid and prolonged hypothermia after hypoxic ischemia

Objective: To determine whether the neurotensin analog NT69L, administered systemically, could induce mild brain hypothermia after asphyxial cardiac a rrest (ACA) in rats. Methods: The study design was experimental, blinded, r andomized, and approved by the animal use committee. All rats had continuou s monitoring of brain temperature and sustained 8 minutes of ACA, resuscita tion, and either saline or NT69L intravenously after return of spontaneous circulation (ROSC). Rats surviving 14 days after ACA had a neurological def icit score (NDS) and a Morris Water Maze (MWM) test. Results: Seven of eigh t rats in each group survived 14 days. Brain temperature was less than 35 d egreesC 13.1 +/- 3 minutes (mean +/- standard deviation) after NT69L vs con trols that remained 37.5 degreesC at the same ambient temperature (p < 0.05 ANOVA). The NT69L group remained below 35 degreesC for 300 +/- 100 minutes while the controls remained at 37.5 +/- 0.5 degreesC. The NDS in the NT69L rats was 3 +/- 3% vs controls 26 +/- 8% (p < 0.05, Kruskal-Wallis, 0% = no rmal, 100% = brain dead). The NT69L rats performed better on the MWM vs the controls (22 +/- 8 see vs 45 +/- 26 see, respectively, p < 0.05 ANOVA). Co nclusions: NT69L induced rapid and prolonged mild brain hypothermia after A CA in this rat model and reduced neurological deficits.