Prolonged drug-induced hypothermia in experimental stroke.
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 degrees C) during 24 hours after bolus injection of Talipexole was significantly lower than in control rats (37.3 +/- 0.5 degrees 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 degrees 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.
Johansen
Flemming Fryd
FF
Molecular Neuropathology Group, University of Copenhagen, Denmark. FFJ@NEPA.KU.DK
Jørgensen
Henrik Stig
HS
Reith
Jakob
J