Cerebral hypoxemia-ischemia and reoxygenation with 21% or 100% oxygen in newborn piglets: effects on extracellular levels of excitatory amino acids and microcirculation

Abstract

Objective: To determine whether reoxygenation with 21% oxygen is preferable to 100% oxygen in normalizing extracellular levels of excitatory amino acids in the brains of hypoxic-ischemic newborn piglets and to compare this model of combined hypoxemia-ischemia to a previously used model of global hypoxemia.

Design: Prospective, randomized animal study.

Setting: Surgical research laboratory.

Subjects: Twenty-four anesthetized piglets, 1-3 days old.

Interventions: Hypoxemia-ischemia was achieved by normoventilation with 8% oxygen and temporary occlusion of the common carotid arteries. After 20 mins, reoxygenation-reperfusion was started with 21% oxygen (HI 21% group, n = 12) or 100% oxygen (HI 100% group, n = 12) for 30 mins followed by 21% oxygen. All piglets were observed for 2 hrs.

Measurements and main results: We measured extracellular concentrations of amino acids in striatum and hypoxanthine in cerebral cortex (microdialysis), microcirculation in cerebral cortex (laser Doppler), plasma hypoxanthine, and mean arterial pressure. During the 2-hr reoxygenation-reperfusion period, levels of amino acids were significantly higher in the HI 21% group compared with the HI 100% group (glutamate, p = 0.02; aspartate, p = 0.03). Mean arterial pressure was significantly lower in the HI 21% group (p = 0.04). Microcirculation decreased to <10% of baseline during hypoxemia-ischemia and normalized during reoxygenation-reperfusion in the HI 100% group, but it remained at a significantly lower level in the HI 21% group (p = 0.03).

Conclusions: Significantly higher levels of excitatory amino acids in striatum, significantly lower mean arterial pressure, and a significantly greater degree of hypoperfusion in cerebral cortex were found after reoxygenation with 21% oxygen compared with 100% oxygen in normocapnic, hypoxemic-ischemic newborn piglets. This suggests a less favorable outcome in the group receiving room air.