DELAYED INDUCTION OF MILD HYPOTHERMIA TO REDUCE INFARCT VOLUME AFTER TEMPORARY MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Deep to moderate hypothermia (24 degrees to 30 degrees C) during focal cerebral ischemia reduces infarct volume but must be initiated before the onset of ischemia to be effective and has deleterious pulmonary, myocardial and neurological effects. It is not known whether mild hypothermia (32 degrees to 33 degrees C) protects against ischemic neuronal damage, whether hypothermia induced after the onset of ischemia has protective effects, or whether these effects are associated with alterations in cortical blood flow. In this study, mild whole-body hypothermia was induced in rats just before or 10, 30, or 60 minutes after the onset of 2 hours of temporary middle cerebral artery occlusion; rewarming began immediately after reversal of occlusion and normothermia was maintained throughout 22 hours of reperfusion. Infarct volume, measured 24 hours after the end of reperfusion, was significantly smaller in rats made hypothermic within 30 minutes after the onset of ischemia than in normothermic controls; hypothermia induced at 60 minutes of ischemia did not reduce infarct volume. Cortical blood flow, measured by laser Doppler ultrasound flowmetry, was not significantly different between groups during ischemia; however, postischemic cortical blood flow correlated positively with total infarct volume. These results indicate that mild hypothermia initiated during temporary focal ischemia in rats can reduce infarct volume without attenuating the reduction in cortical blood flow.