Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia.
OBJECTIVE
External cooling is commonly used to force induction of mild hypothermia but requires equipment, has a slow onset of action, and must be prolonged to provide permanent neurologic benefits after hypoxic-ischemia. It is unknown whether the method for inducing mild hypothermia affects neurologic outcome after near-drowning. The objective of the study was to induce mild hypothermia with neurotensin analog NT77 or external cooling in a rat model of near-drowning. We hypothesize that NT77 would be more effective for improving neurologic outcome than external cooling of the same duration.


METHODS
Rats were randomized to a normothermic control, neurotensin-induced hypothermia, brief external cooling, or prolonged external cooling group after asphyxial cardiac arrest.


METHODS
Laboratory investigation.


METHODS
Forty-eight rats.


METHODS
Mild hypothermia was induced by external cooling for 4 hrs (brief external cooling) or 24 hrs (prolonged external cooling) or by neurotensin-induced hypothermia administration 30 mins after asphyxial cardiac arrest in rats.


METHODS
Outcome was assessed by a neurologic deficit score, the Morris water maze, and CA1 hippocampus histology 15 days after resuscitation.


RESULTS
Neurologic deficit score at 72 hrs after asphyxial cardiac arrest was lower with neurotensin-induced hypothermia (score, 0) and prolonged external cooling (score, 0) vs. normothermic control (score, 20) and brief external cooling (score, 18; p <.05). Latency time in the Morris water maze 15 days after asphyxial cardiac arrest was decreased with neurotensin-induced hypothermia (14+/-11 secs) and prolonged external cooling (18+/-9 secs) vs. normothermic control (74+/-17 secs) and brief external cooling (78+/-18 secs, p <.05). There was less ischemic neuronal damage with neurotensin-induced hypothermia (28+/-24%) and prolonged external cooling (21+/-14%) vs. normothermic control (61+/-32%) and brief external cooling (51+/-32%).


CONCLUSIONS
Neurotensin-induced hypothermia improved neurologic outcome after asphyxial cardiac arrest in rats vs. brief external cooling but was comparable to prolonged external cooling.
Katz
Laurence M
LM
University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Young
Amanda
A
Frank
Jonathan E
JE
Wang
Yuanfan
Y
Park
Kyunam
K
D000818:Animals; D001237:Asphyxia / Q000628:therapy; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000628:therapy; D007036:Hypothermia, Induced / Q000379:methods*; D002534:Hypoxia, Brain / Q000517:prevention & control*; D015701:Near Drowning / Q000628:therapy*; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D018709:Statistics, Nonparametric
D009496:Neurotensin