Abstract
In experimental and human stroke, hypothermia is strongly related to a favorable outcome.
Previous attempts to manipulate the core temperature in focal cerebral ischemia have
been based on mechanical cooling. The purpose of the study is to establish a model
for long-term drug-induced hypothermia in focal ischemia by pharmacological alteration
of the central thermoregulatory set-point. We tested the hypothesis that the dopaminergic
agonist Talipexole, which induces hypothermia, reduces infarct size. Body temperature
was monitored by a radio-pill-implant. Rats had reversible occlusion of the middle
cerebral artery (MCAO) for 30 minutes. Thirty minutes after reflow, the experimental
group of rats (n = 10) received an intravenous bolus injection of Talipexole followed
by a continuous infusion of Talipexole during the following 24 hours. The control
group of rats (n = 10) received a similar treatment regimen with saline only. All
rats were killed 7 days after MCAO. Infarct volume was quantified stereologically.
The mean body temperature (35.6 + 1.0°C) during 24 hours after bolus injection of
Talipexole was significantly lower than in control rats (37.3 ± 0.5°C), P <.05. Infarct volumes were significantly lower in the Talipexole group (4.7 ± 1.9
mm3) than in the control group (8.8 ± 4.7 mm3), P <.04. In the Talipexole treated rats we also observed a significant hypokalemia (P =.001) and a significantly lower index of relative degree of movement (P <.02). Our study shows that the core body temperature was reduced by 1.7 °C for 24
hours after MCAO in rats treated with Talipexole. This treatment induced a significant
reduction of infarct volume at 7 days after focal ischemia by 47%. We suggest that
the reduction in infarct volume is related to drug-induced hypothermia. The hypokalemia
in the hypothermic rats is possibly explained by the observed lower degree of movement.
Copyright © 2003 by National Stroke Association
Keywords
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Article info
Publication history
Accepted:
October 8,
2002
Received:
June 20,
2002
Footnotes
*Funding for this research was provided by The Danish Medical Research Council, Brødrene Hartmanns Foundation, Familien Hede Nielsens Foundation, The Foundation of 1870, Gerda and Aage Haensch Foundation, and the Augustinus Foundation.
**Address reprint requests to Flemming Fryd Johansen, Associate Professor of Neuropathology, Institute of Molecular Pathology, University of Copenhagen, 11 Frederik V vej, DK-2100 Copenhagen, Denmark. E-mail. [email protected]
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© 2003 National Stroke Association. Published by Elsevier Inc. All rights reserved.
