title: The interaction of temperature with thiopental and etomidate on extracellular dopamine and glutamate levels in Wistar-Kyoto rats subjected to forebrain ischemia.
abstract: BACKGROUND
  Many studies demonstrate an association between brain damage and the extracellular release of catecholamines and amino acids during cerebral ischemia. While the clinical value of hypothermia during periods of compromised cerebral blood flow and oxygen delivery is well established, the role 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 thiopental (STP) and etomidate (ETOM) on extracellular neurotransmitter accumulation in the rat corpus striatum during cerebral ischemia.
  
  
  METHODS
  Animals were randomly assigned to one of six subgroups: normal saline (NS-norm, pericranial t approximately equal 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 striatum. Dopamine (DA), glutamate, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were measured. At zero minutes, animals received a 10-min infusion of STP (3 mg x kg(-1) x min(-1)), ETOM (0.6 mg x kg(-1) x min(-1)), or NS. Prior to ischemia, animals were given either intravenous STP (10 mg x kg(-1)), ETOM (3 mg x kg(-1)), or NS in bolus form. Each animal was then subjected to 10 min of forebrain ischemia (Is1) followed by a reperfusion interval (Rep1). The entire sequence was then repeated.
  
  
  RESULTS
  There were significant interactions between temperature and drug for DA (Is1, P=0.006, Is2, P=0.032) and its metabolites (DOPAC, Is1 P=0.01, HVA, Is1 P=0.03), and for glutamate (Is1, P=0.03, Is2 P=0.06). The nature of this interaction differed for DA and glutamate. The reduction in DA accumulation seen during hypothermia was offset by the addition of either STP or ETOM, whereas the addition of these drugs did not affect the reduced 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. However, depending on the temperature condition, the addition of STP or ETOM in our forebrain ischemia model led to unexpected findings. The administration of these agents during normothermia diminished ischemia-induced DA accumulation yet resulted in significantly higher concentrations of extracellular glutamate. In contrast, STP and ETOM during hypothermia were noted to significantly offset the DA-reducing effects of hypothermia.
authors.affiliation: Department of Anesthesiology, St. Luke's-Roosevelt Hospital Center, New York, NY 10019, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Lesser
authors.forename: R
authors.initials: R
authors.lastname: Koorn
authors.forename: J D
authors.initials: JD
authors.lastname: Vloka
authors.forename: M M
authors.initials: MM
authors.lastname: Kuroda
authors.forename: D M
authors.initials: DM
authors.lastname: Thys
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005045:Etomidate / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced; D008297:Male; D017551:Microdialysis; D016548:Prosencephalon / Q000098:blood supply; D051381:Rats; D011921:Rats, Inbred WKY; D015424:Reperfusion; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D015102:3,4-Dihydroxyphenylacetic Acid; D002245:Carbon Dioxide; D018698:Glutamic Acid; D013874:Thiopental; D004298:Dopamine; D006719:Homovanillic Acid; D005045:Etomidate