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(Stroke. 2005;36:665.)
© 2005 American Heart Association, Inc.

Original Contributions

Hyperthermia Masks the Neuroprotective Effects of Tissue Plaminogen Activator

From the Stroke Research Laboratory, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Correspondence to Dr Ashfaq Shuaib, Stroke Research Laboratory, 533 HMRC, University of Alberta, Edmonton, AB, T6G 2S2, Canada. E-mail ashfaq.shuaib{at}ualberta.ca

Background and Purpose— Previously, we have shown that hyperthermia significantly increased neuronal damage after ischemic injury in a focal embolic model of stroke in rats. In the present study, we examined the effects of hyperthermia on the efficacy of thrombolytic therapy in this stroke model.

Methods— In part A, efficacy of tissue plaminogen activator (tPA) treatment was examined in normothermic and hyperthermic rats after embolization of preformed clots into middle cerebral artery (MCA). In part B, brain perfusion deficits were assessed in rats after MCA occlusion. In part C, blood–brain barrier (BBB) permeability was examined in rats after MCA occlusion. In part D, we examined the influence of hyperthermia on fibrinolytic activity of tPA in vitro.

Results— Results showed that treatment with tPA significantly reduced infarct volume in normothermic and 38°C hyperthermic rats. When compared with normothermic rats, perfusion deficits in hyperthermic rats were significantly increased at both 3 hours and 6 hours after ischemic injury. Compared with normothermic sham-operated rats, Evans blue dye extravasation was increased in the injured rats with 39°C hyperthermia. In vitro study showed that hyperthermia increased the fibrinolytic activity of tPA.

Conclusions— The present study shows that hyperthermia masks the neuroprotective effects of tPA treatment after ischemic injury and that this may be caused by increased BBB permeability, increased edema, and early progression of ischemic penumbral region to irreversibly damaged tissue as shown by progressively increasing perfusion deficits in hyperthermic rats.

Key Words: hyperthermia • ischemia • middle cerebral artery • perfusion

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