Neuyotensin-induced hypotheymia 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. 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.