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 after return 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 degrees C 13.1 +/- 3 minutes (mean +/- standard deviation) after NT69L vs controls that remained 37.5 degrees C at the same ambient temperature (p < 0.05 ANOVA). The NT69L group remained below 35 degrees C for 300 +/- 100 minutes while the controls remained at 37.5 +/- 0.5 degrees 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 rat model and reduced neurological deficits.
Katz
L M
LM
Department of Emergency Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. lkatz@med.unc.edu
Wang
Y
Y
McMahon
B
B
Richelson
E
E
D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000150:complications / Q000628:therapy; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D013997:Time Factors
D010446:Peptide Fragments; C407426:neurotensin 69L; D009496:Neurotensin