Mild hypothermia on anoxic depolarization and subsequent cortical injury following transient ischemia

Anoxic depolarization (AD) is one of the major physiological characteristic s in the ischemic core. The effect of mild hypothermia on the appearance of AD and subsequent brain injury following profound ischemia is studied to e valuate the protective mechanism of hypothermia against severe ischemia. Sp rague-Dawley rats were subjected to transient ischemia by hypotension (50-2 0 mmHg) and bilateral carotid artery occlusion (BCA-O) for 20 min in normot hermia and 30 min in hypothermia. The temperature of body and temporal musc les was maintained at 37.5 degrees C and 36.5 degrees C in normothermia and 33.0 degrees C and 31.0 degrees C in hypothermia, respectively. Recording of the DC potential shift and electrocorticogram and monitoring of the cort ical blood flow (CoBF) with a laser Doppler flowmeter were done epidurally on the right parietal cortex. The right parietal cortex pathology was exami ned 24 h after ischemia in normothermia and after 30 days in hypothermia. A D appeared in all seven normothermic rats with a fall in the CoBF to 9%-10% of the control flow. However, in spite of CoBF reduction to 8%-9% of the c ontrol flow, it did not appear in five hypothermic rats. Intra-ischemic CoB F was not statistically different between these two groups. AD appeared wit h the CoBF decreasing to 4%-5% of the control flow in seven hypothermic rat s. Intra-ischemic CoBF in hypothermic rats exhibiting AD was significantly lower than the other two groups. The interval between BCA-O and the appeara nce of AD in hypothermic rats was 5.1 +/- 0.3 min (mean +/- SE), which was significantly longer than the 2.2 +/- 0.5 min observed in normothermia (p < 0.0005). Of seven normothermic rats exhibiting AD, two died within 24 h an d four revealed massive neuronal injury. Of seven hypothermic rats with AD, four died between day 2 and day 13, and one revealed diffuse cerebral infa rction. However, no severe ischemic injury or ischemic death was observed i n all five hypothermic rats without AD. The incidence of severe neuronal in jury or ischemic death was significantly lower in hypothermic rats without AD compared with normothermic rats with AD (p < 0.02) or hypothermic rats w ith AD (p < 0.05). Although mild hypothermia delays AD, it is suggested tha t raising the cerebral blood flow threshold for AD appearance has a key rol e in the hypothermic protection of a severely ischemic area such as the isc hemic core.