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

Abstract

Background and Purpose: 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, had 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°C to 38°C, 39°C, or 40°C. Changes in rectal temperature and blood glucose concentration were evaluated during and just 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°C hyperthermia, cortical and total infarct volumes were markedly greater (92.2±63.1 and 126±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°C hyperthermia (16.5±28.7 and 40.9±34.3 mm3) (P