The interaction of temperature with thiopental and etomidate on extracellular dopamine and glutamate levels in Wistar-Kyoto rats subjected to forebrain ischemia

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.