Neurotensin analog NT69L induces rapid and prolonged hypothermia after hypoxic ischemia.

Abstract

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.

• Authors: L M Katz, Y Wang, B McMahon, E Richelson
• Journal: Academic emergency medicine : official journal of the Society for Academic Emergency Medicine (Acad Emerg Med) Vol. 8 Issue 12 Pg. 1115-21 (Dec 2001) ISSN: 1069-6563 [Print] United States
• PMID: 11733287 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Peptide Fragments
• neurotensin 69L
• Neurotensin

Topics

• Analysis of Variance
• Animals
• Blood Gas Analysis
• Cardiopulmonary Resuscitation
• Disease Models, Animal
• Heart Arrest (complications, therapy)
• Hypothermia (chemically induced, physiopathology)
• Hypoxia-Ischemia, Brain (etiology, prevention & control)
• Infusions, Intravenous
• Male
• Neurotensin (administration & dosage, analogs & derivatives, pharmacology)
• Peptide Fragments (administration & dosage, pharmacology)
• Probability
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reference Values
• Sensitivity and Specificity
• Time Factors