NEUROPROTECTION WITH PROLONGED HEAD COOLING STARTED BEFORE POSTISCHEMIC SEIZURES IN FETAL SHEEP

Objective. Cerebral hypothermia has been shown to reduce damage from e xperimental hypoxia-ischemia if started shortly after reperfusion. How ever, in the newborn infant it may not be feasible to determine progno sis so soon after exposure to asphyxia. The aim of this study was to d etermine whether head cooling, delayed until shortly before the onset of postasphyxial seizure activity, is neuroprotective. Methods. Unanes thetized near-term fetal sheep in utero were subjected to 30 minutes o f cerebral ischemia. Later, at 5.5 hours, they were randomized to eith er cooling (n = 7) or sham cooling (n = 10) for 72 hours. Intrauterine cooling was induced by circulating cold water through a coil around t he fetal head. The water temperature was titrated to reduce fetal extr adural temperature from 39.1 +/- 0.1 degrees C to between 30 degrees C and 33 degrees C, while maintaining esophageal temperature >37 degree s C. Results. Cerebral cooling suppressed the secondary rise in cortic al impedance (a measure of cytotoxic edema), but did not prevent delay ed seizures, 8 to 30 hours after ischemia. Transient metabolic changes including increased plasma lactate and glucose levels were seen with a moderate sustained rise in blood pressure. This severe cerebral insu lt resulted in depressed residual parietal electroencephalographic act ivity after 5 days recovery (-14.2 +/- 1.5 decibels), associated with a watershed distribution of neuronal loss leg, 94 +/- 4% in parasagitt al cortex and 77 +/- 4% in the lateral cortex). Hypothermia was associ ated with better recovery of electroencephalographic activity (-8.9% /- 1.8 decibels) and substantially reduced neuronal loss in the parasa gittal cortex (46 +/- 13%), the lateral cortex (9 +/- 4%), and other r egions except the cornu ammonis sectors 1 and 2 of the hippocampus. Co nclusions. Delayed selective head cooling begun before the onset of po stischemic seizures and continued for 3 days may have potential to sig nificantly improve the outcome of moderate to severe hypoxic-ischemic encephalopathy.