EFFECT OF ETOMIDATE ON IN-VIVO ISCHEMIA-INDUCED DOPAMINE RELEASE IN THE CORPUS STRIATUM OF THE RAT - A STUDY USING CEREBRAL MICRODIALYSIS

Dopamine (DA) is released in large quantities into the corpus striatum during cerebral ischemia and may exacerbate tissue damage. Using cerebral microdialysis, we studied the effect of etomidate on in vivo ischemia-induced DA release in rat corpus striatum. Reversible cerebral ischemia was induced by using carotid ligatures and hypovolemic hypotension, and monitored with laser Doppler flowmetry. After baseline measurements, 20 normothermic, anesthetized rats were subjected to three separate periods of cerebral ischemia, interrupted by 45- to 75-min periods of reperfusion. The rats were randomized into two groups. All rats received 400 mg/kg of intraperitoneal chloral hydrate for induction of anesthesia. In Group I (it = 10) anesthesia was maintained using additional intraperitoneal chloral hydrate 100 mg/kg every 2 h. Group II received etomidate 0.6 mg/kg 10 min before the first episode of cerebral ischemia, followed by an infusion of 60 mu g.kg(-1).min(-1). Before each subsequent period of induced ischemia, an additional dose of etomidate (0.6 mg/kg) was administered. DA levels were approximately 350 times above baseline in Group I during the three ischemic episodes (IS1, IS2, and IS3). In Group II, ischemia-induced DA release was significantly attenuated (by 79%) during IS1, IS2, and IS3 compared to Group I(P < 0.01). DA levels did not significantly change in magnitude during the three ischemic episodes in either group. The levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were reduced by 40%-70% during IS1, IS2, and IS3 (compared to the baseline and first and second reperfusion periods) in Group I, with a significantly smaller decline during IS1, IS2, and IS3 in Group II. Thus etomidate significantly reduced the magnitude of ischemia-induced DA release, whereas DA metabolism was preserved. We believe that this phenomenon is related to etomidate's brain protective profile.