MILD HYPOTHERMIA REDUCES INFARCT SIZE RESULTING FROM TEMPORARY BUT NOT PERMANENT FOCAL ISCHEMIA IN RATS

Background and Purpose: Mild hypothermia (32-35-degrees-C) has been repeatedly shown in laboratory models to reduce damage resulting from global cerebral ischemic insults. Little information is available, however, regarding the protective potential of mild hypothermia against focal ischemia. We designed the present study to determine whether mild hypothermia influences outcome from either temporary or permanent middle cerebral artery occlusion in the rat. Methods: In experiment 1 (permanent occlusion), mechanically ventilated, halothane-anesthetized spontaneously hypertensive rats underwent permanent ligation of the middle cerebral artery. Pericranial temperature was maintained at either 37-degrees-C (n = 11) or 33-degrees-C (n = 11) during the first 2 hours of occlusion. In experiment 2 (temporary occlusion), the vessel was occluded for 1 hour only. Pericranial temperature was controlled at either 37-degrees-C (n = 12) or 33-degrees-C (n = 14) during ischemia and for 1 hour after reperfusion. In both experiments, the rats were allowed to recover, with neurological function scored at 24 and 96 hours after onset of ischemia. Cerebral infarct volume (as determined by nitro blue tetrazolium staining) was planimetrically evaluated 96 hours after onset of ischemia. Results: No difference in infarct volume was observed between groups undergoing permanent occlusion (177 +/- 53 mm3 for 37-degrees-C rats, 167 +/- 71 mm3 for 33-degrees-C rats [mean +/- SD]). Although neurologic function correlated with infarct volume at 96 hours (all animals in experiment 1 combined; p < 0.01), we were unable to demonstrate an intergroup difference in function. In animals undergoing temporary occlusion, mean +/- SD infarct volume was 48% less in the hypothermic group (89 +/- 54 mm3 for 37-degrees-C, 46 +/- 31 mm3 for 33-degrees-C; p < 0.03). Neurological function again correlated with infarct size (p < 0.02), but improvement in function approached significance for the hypothermic group (p < 0.06) at 24 hours after reperfusion only. Conclusions: Benefits from mild hypothermia may be obtained under conditions of temporary but not permanent middle cerebral artery occlusion in the rat.