DELAYED POSTISCHEMIC HYPERTHERMIA IN AWAKE RATS WORSENS THE HISTOPATHOLOGICAL OUTCOME OF TRANSIENT FOCAL CEREBRAL-ISCHEMIA

Background and Purpose Over the past several years, it has been demons trated that mild intraischemic or immediate postischemic hyperthermia worsens ischemic outcome in models of global and focal ischemia. Perio ds of hyperthermia are commonly seen in patients after stroke and card iac arrest. The hypothesis tested in this study was that a brief hyper thermic period, even when occurring days after an ischemic insult, has detrimental effects on the pathological outcome of focal ischemia. Me thods Rats were subjected to 60 minutes of transient middle cerebral a rtery occlusion by insertion of an intraluminal filament. Twenty-four hours after reperfusion, awake rats were subjected to temperature modu lation for 3 hours in a heating chamber. The brain temperature was equ ilibrated to either 37 degrees C to 38 degrees C, 39 degrees C, or 40 degrees C. Changes in rectal temperature and blood glucose concentrati on were evaluated during and just after temperature modulation. Behavi oral tests were also assessed. Three days after temperature modulation , brains were perfusion-fixed, and infarct volumes were determined. Re sults In animals with 40 degrees C hyperthermia, cortical and total in farct volumes were markedly greater (92.2+/-63.1 and 126.5+/-72.3 mm(3 ) [mean+/-SD], respectively) than in normothermic rats (14.4+/-12.7 an d 42.4+/-19.2 mm(3)) and in animals with 39 degrees C hyperthermia (16 .5+/-28.7 and 40.9+/-34.3 mm(3)) (P<.05), whereas there was no signifi cant difference between normothermic and 39 degrees C hyperthermic ani mals. In addition, animals with 40 degrees C hyperthermia displayed wo rsened neurological scores compared with normothermic and 39 degrees C hyperthermic rats. In the 39 degrees C hyperthermia group, rectal tem peratures were significantly lower (by 0.2 degrees C to 0.5 degrees C) than brain temperatures throughout the modulation period. Conclusions The present findings provide evidence that, after a transient focal i schemic insult, the postischemic brain becomes abnormally sensitive to the effects of delayed temperature elevation, even of moderate degree . The threshold for aggravation of ischemic injury by delayed hyperthe rmia appears to be approximately 40 degrees C. Body-temperature measur ements, in both awake and anesthetized animals, may not accurately ref lect brain temperature under these conditions. The present study stres ses that fever of even moderate degree in the days following brain isc hemia may markedly exacerbate brain injury.