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 arrest (ACA) in rats. Methods: The study design was experimental, blinded, randomized, and approved by the animal use committee. All rats had continuous monitoring of brain temperature and sustained 8 minutes of ACA, resuscitation, and either saline or NT69L intravenously afterreturn of spontaneous circulation (ROSC). Rats surviving 14 days after ACA had a neurological deficit score (NDS) and a Morris Water Maze (MWM) test. Results: Seven of eight rats in each group survived 14 days. Brain temperature was less than 35°C 13.1 ± 3 minutes (mean ± standard deviation) after NT69L vs controls that remained 37.5°C at the same ambient temperature (p < 0.05 ANOVA). The NT69L group remained below 35°C for 300 ± 100 minutes while the controls remained at 37.5 ± 0.5°C. The NDS in the NT69L rats was 3 ± 3% vs controls 26 ± 8% (p < 0.05, Kruskal-Wallis, 0%= normal, 100%= brain dead). The NT69L rats performed better on the MWM vs the controls (22 ± 8 sec vs 45 ± 26 sec, respectively, p < 0.05 ANOVA). Conclusions: NT69L induced rapid and prolonged mild brain hypothermia after ACA in this ratmodel and reduced neurological deficits.