The effects of CO2 levels and body temperature on brain interstitial pH alterations during the induction of hypoxic-ischemic encephalopathy in newborn pigs.

ABSTRACT

Brain interstitial pH (pHbrain) alterations play a crucial role in the development of hypoxic-ischemic (HI) encephalopathy (HIE) caused by asphyxia in neonates. The newborn pig is one of the most suitable large animal models for studying HIE, however, compared to rats, experimental data on pHbrain alterations during HIE induction are limited. The major objective of the present study was thus to compare pHbrain changes during HIE development induced by experimental normocapnic hypoxia (H) or asphyxia (A), elicited with ventilation of a gas mixture containing 6%O2 or 6%O2/20%CO2, respectively for 20 min, under either normothermia (NT) or hypothermia (HT) (38.5 ± 0.5 °C or 33.5 ± 0.5 °C core temperature, respectively) in anesthetized piglets yielding four groups H-NT, A-NT, H-HT, and A-HT. pHbrain changes during HI stress and the 60 min reoxygenation period were measured using a pH-selective microelectrode inserted into the parietal cortex through an open cranial window. In all groups, the pHbrain response to HI stress was acidosis, at the nadir pHbrain values dropped from the baseline of 7.27 ± 0.02 to H-NT5.93 ± 0.30, A-NT5.90 ± 0.52, H-HT6.81 ± 0.27, and A-HT6.27 ± 0.24 indicating that (1) H and A elicited similar, severe brain acidosis under NT greatly exceeding pH changes in arterial blood (pHa dropped to 7.24 ± 0.07 and 6.78 ± 0.03 from 7.52 ± 0.06 and 7.50 ± 0.05, respectively), and (2) HT ameliorated more the brain acidosis induced by H than by A. In all four groups, pHbrain was restored to baseline values without an alkalotic overshoot during the observed reoxygenation, Our findings suggest that under NT either H or A - both commonly employed HI stresses to elicit HIE in piglet models - would result in a similar acidotic pHbrain response without an alkalotic component either during the HI stress or the early reoxygenation period.