Effects of hypothermia for a short period on histologic outcome and extracellular glutamate concentration during and after cardiac arrest in rats

Abstract

Objective: To evaluate the therapeutic effects of hypothermia for a short period (20 mins, 31 degrees C) using a cardiac arrest model (5 mins) in rats.

Design: Prospective animal study.

Setting: Experimental laboratory in a university hospital.

Subjects: Male Wistar rats (n = 42).

Intervention: Direct current (DC) potential and extracellular glutamate concentrations (microdialysis) were monitored in the hippocampal region. Histologic observation was performed 7 days later.

Measurements and main results: No animal died or showed severe complications as a result of hypothermia for a short period. In nontreated animals (group F), extracellular glutamate concentration simultaneously increased with the onset of membrane depolarization and continued to increase during the reperfusion period (maximum, 212% +/- 40% of the pre-ischemia level) until the onset of DC recovery. In animals in which hypothermia was initiated before the onset of ischemia (group A), extracellular glutamate concentration did not increase during the ischemia period. When hypothermia was initiated at the onset of resuscitation (group B), the glutamate concentration immediately decreased. In animals in which hypothermia was initiated at 4.9 +/- 1.3 mins (immediately after DC recovery, group C), 10 mins (group D), and 20 mins (group E) after the onset of resuscitation, changes in extracellular glutamate concentration were the same as those in nontreated animals. The percentage of injured neurons was significantly attenuated (compared with group F, 82% +/- 10%) when hypothermia was initiated before DC recovery (group A, 5% +/- 3%; group B, 29% +/- 22%) or immediately after DC recovery (group C, 58% +/- 18%, 9.9 +/- 1.3 mins after the onset of ischemia).

Conclusions: Hypothermia for a short period decreased glutamate concentration when it was initiated before DC recovery and attenuated neuronal damage when it was initiated before or immediately after DC recovery. The therapeutic time window for hypothermia for a short period is about 10 mins after the onset of ischemia.