An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies

The purpose of this study was to develop a newborn piglet model of hypoxia/ischaemia which would better emulate the clinical situation in the asphyxiated human neonate and produce a consistent degree of histopathological injury following the insult. One-day-old piglets ( n=18) were anaesthetised with a mixture of propofol (10 mg/kg/h) and alfentinal (55.5 μg/kg/h) i.v. The piglets were intubated and ventilated. Physiological variables were monitored continuously. Hypoxia was induced by decreasing the inspired oxygen (FiO 2) to 3–4% and adjusting FiO 2 to maintain the cerebral function monitor peak amplitude at ≤5 μV. The duration of the mild insult was 20 min while the severe insult was 30 min which included 10 min where the blood pressure was allowed to fall below 70% of baseline. Control piglets ( n=4 of 18) were subjected to the same protocol except for the hypoxic/ischaemic insult. The piglets were allowed to recover from anaesthesia then euthanased 72 h after the insult. The brains were perfusion-fixed, removed and embedded in paraffin. Coronal sections were stained by haematoxylin/eosin. A blinded observer examined the frontal and parietal cortex, hippocampus, basal ganglia, thalamus and cerebellum for the degree of damage. The total mean histology score for the five areas of the brain for the severe insult was 15.6±4.4 (mean±S.D., n=7), whereas no damage was seen in either the mild insult ( n=4) or control groups. This ‘severe damage’ model produces a consistent level of damage and will prove useful for examining potential neuroprotective therapies in the neonatal brain.