Delayed postischemic hyperthermia in awake rats worsens the histopathological outcome of transient focal cerebral ischemia.

OBJECTIVE

Over the past several years, it has been demonstrated that mild intraischemic or immediate postischemic hyperthermia worsens ischemic outcome in models of global and focal ischemia. Periods of hyperthermia are commonly seen in patients after stroke and cardiac arrest. The hypothesis tested in this study was that a brief hyperthermic period, even when occurring days after an ischemic insult, has detrimental effects on the pathological outcome of focal ischemia.

METHODS

Rats were subjected to 60 minutes of transient middle cerebral artery occlusion by insertion of an intraluminal filament. Twenty-four hours after reperfusion, awake rats were subjected to temperature modulation for 3 hours in a heating chamber. The brain temperature was equilibrated to either 37 degrees C to 38 degrees C, or 40 degrees C. Changes in rectal temperature and blood glucose concentration were evaluated during and just after temperature modulation. Behavioral tests were also assessed. Three days after temperature modulation, brains were perfusion-fixed, and infarct volumes were determined.

RESULTS

In animals with 40 degrees C hyperthermia, cortical and total infarct volumes were markedly greater (92.2 +/- 63.1 and 126.5 +/- 72.3 mm3 [mean +/- SD], respectively) than in normothermic rats (14.4 +/- 12.7 and 42.4 +/- 19.2 mm3) and in animals with 39 degrees C hyperthermia (16.5 +/- 28.7 and 40.9 +/- 34.3 mm3) (P < .05), whereas there was no significant difference between normothermic and 39 degrees C hyperthermic animals. In addition, animals with 40 degrees C hyperthermia displayed worsened neurological scores compared with normothermic and 39 degrees C hyperthermic rats. In the 39 degrees C hyperthermia group, rectal temperatures were significantly lower (by 0.2 degree C to 0.5 degree C) than brain temperatures throughout the modulation period.

CONCLUSIONS

The present findings provide evidence that, after a transient focal ischemic 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 hyperthermia appears to be approximately 40 degrees C. Body-temperature measurements, in both awake and anesthetized animals, may not accurately reflect brain temperature under these conditions. The present study stresses that fever of even moderate degree in the days following brain ischemia may markedly exacerbate brain injury.