Cerebral Blood Flow and Metabolism in Ovine Fetuses During Asphyxia Resulting in Seizures

Abstract

Severe fetal asphyxia can cause neurologic damage, but little is known about cerebral oxidative metabolism under these conditions. This study was designed to measure cerebral blood flow and oxygen consumption during severe global asphyxia in fetal sheep, asphyxiated to the point at which seizure activity subsequently occurred. Six sheep were chronically instrumented with fetal electrodes, fetal and maternal vascular catheters, and an adjustable occluder on the maternal common hypogastric artery. Measurements were made of fetal arterial blood gases, blood pressure, heart rate electrocorticogram (ECoG), nuchal muscle electromyogram (EMG), and regional blood flow (radioactive microspheres) during control, and at 30 and 60 min after complete occlusion of the maternal hypogastric artery. The ECoG became isoelectric, and the fetuses developed a marked respiratory and metabolic acidosis, the pH falling to 6.99 ± 0.03, the pCO₂ rising to 73 ± 11 mm Hg, and base excess falling to −16 ± 1 mEq/L at 60 min of occlusion. Control fetal arterial blood pressure was 52 ± 9 mm Hg and did not change significantly with asphyxia at 60 min. Cerebral cortical blood flow was 127 ± 54 ml/100 g/min at control, and 204 ± 130 ml/100 g/min at 60 min of asphyxia. Cerebral oxygen consumption was 201 ± 50 μM/100 g/min at control, and 76 ± 57 μM/100 g/min at 60 min of asphyxia (P < 0.05), i.e., 45% of control. All 6 fetuses had episodic seizure activity based on ECoG and nuchal EMG activity, beginning 50 ± 47 min after release of the occluder. This seizure activity continued for 24-36 h. This study shows that 60 min of asphyxia associated with suppressed ECoG activity and severe acidosis induced neuronal damage, manifesting as seizure activity, and that this occurred when cerebral oxidative metabolism was reduced to ≤50% of control.

Key Words:

• Ovine fetus
• Asphyxia
• Cerebral metabolism
• Seizures