The interaction of temperature with thiopental and etomidate on extracellular dopamine and glutamate levels in Wistar-Kyoto rats subjected to forebrain ischemia
Jb. Lesser et al., The interaction of temperature with thiopental and etomidate on extracellular dopamine and glutamate levels in Wistar-Kyoto rats subjected to forebrain ischemia, ACT ANAE SC, 43(10), 1999, pp. 989-998
Citations number
28
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Background: Many studies demonstrate an association between brain damage an
d the extracellular release of catecholamines and amino acids during cerebr
al ischemia. While the clinical value of hypothermia during periods of comp
romised cerebral blood flow and oxygen delivery is well established, the ro
le of anesthetic agents is less clear. Furthermore, the interaction between
these agents and hypothermia remains to be elucidated. The purpose of this
study was to examine the interactive effects of temperature, sodium thiope
ntal (STP) and etomidate (ETOM) on extracellular neurotransmitter accumulat
ion in the rat corpus striatum during cerebral ischemia.
Methods: Animals were randomly assigned to one of six subgroups: normal sal
ine (NS-norm, pericranial t approximate to 37 degrees C, and NS-hypo, t=30
degrees C), etomidate (ETOM-norm and ETOM-hypo), and sodium thiopental (STP
-norm and STP-hypo). Microdialysis probes were inserted into the corpus str
iatum. Dopamine (DA), glutamate, 3,4-dihydroxyphenylacetic acid (DOPAC) and
homovanillic acid (HVA) levels were measured. At zero minutes, animals rec
eived a 10-min infusion of STP (3 mg.kg(-l). min(-1)), ETOM (0.6 mg.kg(-1).
min(-1)), or NS. Prior to ischemia, animals were given either intravenous S
TP (10 mg.kg(-1)), ETOM (3 mg.kg(-1)), or NS in bolus form. Each animal was
then subjected to 10 min of forebrain ischemia (Is(1)) followed by a reper
fusion interval (Rep(-1)). The entire sequence was then repeated.
Results: There were significant interactions between temperature and drug f
or DA (Is(1), P=0.006, Is(2) P=0.032) and its metabolites (DOPAC, Is(1) P=0
.01, HVA, Is(1) P=0.03), and for glutamate (Is(1), P=0.03, Is(2) P=0.06). T
he nature of this interaction differed for DA and glutamate. The reduction
in DA accumulation seen during hypothermia was offset by the addition of ei
ther STP or ETOM, whereas the addition of these drugs did not affect the re
duced glutamate levels seen with hypothermia. During normothermia, STP and
ETOM resulted in diminished DA accumulation compared to controls, yet they
increased the accumulation of extracellular glutamate.
Conclusions: Consistent with other studies, hypothermia was associated with
diminished extracellular DA concentrations during forebrain ischemia. Howe
ver, depending on the temperature condition, the addition of STP or ETOM in
our fore-brain ischemia model led to unexpected findings. The administrati
on of these agents during normothermia diminished ischemia-induced DA accum
ulation yet resulted in significantly higher concentrations of extracellula
r glutamate. In contrast, STP and ETOM during hypothermia were noted to sig
nificantly offset the DA-reducing effects of hypothermia.