Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia.

Abstract

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.

DESIGN:

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

SETTING:

Laboratory investigation.

SUBJECTS:

Forty-eight rats.

INTERVENTIONS:

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.

MEASUREMENTS:

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

MAIN 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.

• Authors: Laurence M Katz, Amanda Young, Jonathan E Frank, Yuanfan Wang, Kyunam Park
• Journal: Critical care medicine (Crit Care Med) Vol. 32 Issue 3 Pg. 806-10 (Mar 2004) ISSN: 0090-3493 [Print] United States
• PMID: 15090966 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Neurotensin

Topics

• Animals
• Asphyxia (therapy)
• Disease Models, Animal
• Heart Arrest (therapy)
• Hypothermia, Induced (methods)
• Hypoxia, Brain (prevention & control)
• Near Drowning (therapy)
• Neurotensin (analogs & derivatives, therapeutic use)
• Random Allocation
• Rats
• Statistics, Nonparametric