A limited interval of delayed modest hypothermia for ischemic brain resuscitation is not beneficial in neonatal swine

This investigation determined if a short interval of modest hypothermia (1 h) initiated 30 min after brain ischemia provided neuroprotection. The rati onale for the time and duration of brain cooling reflects the likelihood th at the implementation of neuroprotective strategies will occur at an interv al shortly after ischemia, and that long- term maintenance of normothermia is a cornerstone of neonatal stabilization. Studies were performed in 22 ve ntilated neonatal mini-swine in a superconducting magnet to obtain P-31 mag netic resonance spectra. After a control period all animals underwent 15 mi n of global brain ischemia and were maintained normothermic for the first 3 0 min post-ischemia. In one group of 11 swine normothermia was continued. I n the other group of 11 swine, modest hypothermia was initiated at 30 min p ost-ischemia, continued for 1 h and followed by resumption of normothermia. Animals were subsequently weaned from ventilator support, removed from the magnet, and underwent neurobehavioral and histologic assessment at 72 h po st-ischemia. Both groups had similar severity of ischemia, as indicated by identical changes in arterial blood pressure and pH, alterations in brain b eta-nucleotide triphosphate (% of control where control = 100%, 32 +/- 28 v s 27 +/- 26% for normothermic and hypothermic groups, respectively), and th e extent of intraischemic brain acidosis (6.13 +/- 0.19 vs 6.14 +/- 0.14 fo r normothermic and hypothermic groups, respectively). In both groups the di stribution of stages of encephalopathy were the same: 1 normal and 10 abnor mal (4 mild, 2 moderate, and 4 severe) normothermic, and, 3 normal and 8 ab normal (4 mild, 2 moderate, and 2 severe) hypothermic animals. There was no difference in the extent of neuronal injury between groups. We conclude th at a l-h interval of modest hypothermia initiated at 30 min post-ischemia d oes not confer neuroprotection.