2007, Piran, Slovenia

Cold physiology
EFFECT OF URAPIDIL ON CEREBRAL GLUCOSE UTILISATION
DURING REWARMING OF MILD HYPOTHERMIC RATS.
Karl Peter Ittner, Johann Schoenberge, Markus Zimmermann, Joerg Marienhagen, Kai
Taeger
Universityhospital of Regensburg, Germany
Contact person: karl-peter.ittner@klinik.un-r.de
INTRODUCTION
Serotonin1A-receptors (5-HT1A) are present in high density in the hippocampus, hypothalamus
and neocortex and in the raphe nuclei. According to this distribution 5-HT1A agonists have a
complex influence on brain function: regulation of proprioception, temperature and blood
pressure regulation and inhibition of neuronal activity (1). Urapidil is an approved drug
against hypertension with a dual receptor activity (α1-Adrenoceptorantagonist/5-HT1A-
Receptoragonist) (2). It is unknown whether urapidil could influence brain glucose
metabolism due to its 5-HT-1A agonistic activity. Therefore, we investigated the effect of
urapidil on cerebral glucose utilisation during rewarming after mild hypothermia in the rat.
METHODS
Design: Animal, prospective, randomised study; Mild hypothermia of Sprague Dawley rats
(8/group) was performed by surface cooling (33.2 ± 0,5°C) and followed by 4 treatments:
group 1: convective air rewarming after placebo (NaCl 0.9%); group 2: convective air
rewarming after 5 mg/kg urapidil i.v., 3: normothermic control; 4: hypothermic control. Brain
glucose metabolism during 20 min. of rewarming was assessed by [18 F]2-fluoro-2-deoxy-Dglucose
(FDG) and positron emission tomography (PET, Siemens ECAT, EXACT). FDG
image sets consisted of 47 planes. ROIs (region of interest) for the liver and the whole brain
were drawn manually according to a rat anatomy atlas. Average values of FDG activity of 5
consecutive ROIs in the brain and the liver of each animal were calculated. The depicted
values are the means and SD of brain/liver ratios. Statistical analysis was performed with
ANOVA and post hoc t-tests.
RESULTS
FDG activity of liver and brain within the groups were homogen. Blood glucose
concentrations between and within the groups showed no statistical difference. 20 min. of
rewarming showed a higher (p < 0.001) rectal temperature in the animals treated with urapidil
(36.6 ± 0,4 °C) versus placebo (35.5 ± 0,4°C). After rewarming, there was no statistical
significant difference in the FDG activity ratio between the normothermic urapidil-group and
the mild hypothermic placebo-group (Figure).
DISCUSSION
Rewarming with urapidil of mild hypothermic rats did not increase glucose metabolism in the
rat brain. The glucose metabolism in the normothermic, urapidil-treated rats was similar to the
mild hypothermic animals treated with placebo. This effect could be caused by the 5-HT-1A
agonistic activity of urapidil in the brain. Our result is in accordance with a study, showing
that urapidil inhibited the activity of hippocampal and cortical neurons with neuroprotective
activity in a model of focal and global cerebral ischemia in rodents (3).
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