Xenon/Hypothermia Neuroprotection Regimes in Spontaneously Breathing Neonatal Rats After Hypoxic-Ischemic Insult: The Respiratory and Sedative Effects

Abstract

Hypothermia (HT) reduces neuronal injury after perinatal asphyxia. The anesthetic gas xenon (XE) may enhance this effect. We investigated the sedative and respiratory effects of variable XE concentrations at 37 degrees C normothermia (NT) or 32 degrees C HT after a hypoxic-ischemic (HI) insult to determine the concentration at which XE was a respiratory depressant in spontaneously breathing 7-day-old rat pups. (I) In three control groups, the effects of fasting at NT and HT were investigated. (II) Six groups were subjected to a HI insult (left carotid ligation then 90 min breathing 8% oxygen); three then breathed Air, 50%Xe or 70%Xe for 5 h at NT (NT(Air), NT(50%Xe), NT(70%Xe)), while three breathed identical mixtures during HT (HT(Air), HT(50%Xe), or HT(70%Xe)), in addition to a control group. Blood gases, glucose, and lactate were measured. Sedation (spontaneous movement/respiratory rate) was recorded. Blood chemistry data were successfully obtained from 70 pups. (I) Pups maintained normal blood gas, glucose, and lactate values after 9 h fasting at NT or HT. (II) After HI insult, in comparison with control and NT(Air) groups, 70%Xe at both NT and HT produced higher PCO2 and lower pH values while the HT(Air) and HT(50%Xe) groups only had lower pH values. The HT(70%Xe) combination produced the highest PCO2 and lowest pH values (56.8 mm Hg, 7.35, respectively) and the greatest sedative effect. After HI insult, 70%Xe at both NT and HT induced sedation, respiratory depression, CO2 retention, and a decrease in pH relative to air and control groups. The effects were largely avoided with 50%Xe.