Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

Mild therapeutic hypothermia (HT) reduces brain injury in survivors after perinatal asphyxia. Recent guidelines suggest that resuscitation of term infants should be started with air, but supplemental oxygen is still in use. It is not known whether supplemental oxygen during resuscitation affects the protection offered by subsequent HT.Wilcoxon median (95% confidence interval) hippocampal injury scores (range 0.0-4.0; 0 to ≥90% injury) were 21% O(2) normothermia (NT): 2.00 (1.25-2.50), 21% O(2) HT: 1.00 (0.50-1.50), 100% O(2) NT: 2.50 (1.50-3.25), and 100% O(2) HT: 2.00 (1.25-2.50). Although HT significantly reduced hippocampal injury (B = -0.721, SEM = 0.297, P = 0.018), reoxygenation with 100% O(2) increased injury (B = +0.647, SEM = 0.297, P = 0.033). Regression constant B = 1.896, SEM = 0.257 and normally distributed residuals.We confirm an ~50% neuroprotective effect of therapeutic HT in the neonatal rat. Reoxygenation with 100% O(2) increased injury and worsened reflex performance. HT was neuroprotective whether applied after reoxygenation with air or 100% O(2). However, HT after 100% O(2) gave no net neuroprotection.In an established neonatal rat model, hypoxia-ischemia (HI) was followed by 30-min reoxygenation in either 21% O(2) or 100% O(2) before 5 h of NT (37 °C) or HT (32 °C). The effects of HT and 100% O(2) on histopathologic injury in the hippocampus, basal ganglia, and cortex, and on postural reflex performance 7 d after the insult, were estimated by linear regression.