Effect of Nitrous Oxide on Neuronal Damage and Extracellular Glutamate Concentration as a Function of Mild, Moderate, or Severe Ischemia in Halothane-anesthetized Gerbils

Abstract

The effect of nitrous oxide on ischemic neuronal damage was quantitatively evaluated by use of logistic regression curves. Seventy-two gerbils were anesthetized with 1% halothane and randomly assigned to receive 70% nitrous oxide or 70% nitrogen. Forebrain ischemia was performed for 3, 5, or 7 min, and direct-current potential in the hippocampal CA1 region was recorded. Histologic outcome was evaluated 5 days later. Relations of neuronal damage with ischemic duration and duration of ischemic depolarization were determined by logistic regression curves. In some animals, extracellular glutamate concentration was measured every 60 s during forebrain ischemia. Nitrous oxide increased neuronal damage only with 5 min of ischemia (nitrous oxide vs. nitrogen: 78.5 +/- 23.0 vs. 37.3 +/- 12.2%; P < 0.01). The percentages of neuronal damage with 3 and 7 min of ischemia were not different with or without nitrous oxide. Logistic regression curves indicated that nitrous oxide significantly increased neuronal damage during the period from 3.07 to 6.63 min of ischemia. Logistic regression curves also indicated that nitrous oxide increased neuronal damage in the condition of the same duration of ischemic depolarization. Nitrous oxide shortened the ischemic duration necessary for causing 50% neuronal damage by 0.82 min. Dynamic change in extracellular glutamate concentration was not different (mean maximum dialysate glutamate concentration: 4.29 +/- 3.09 vs. 4.63 +/- 1.83 microm). Administration of nitrous oxide caused an increase in ischemic neuronal damage, but a significant adverse effect was observed with a limited range of ischemic intervals.