MIVAZEROL INHIBITS INTRATHECAL RELEASE OF GLUTAMATE EVOKED BY HALOTHANE WITHDRAWAL IN RATS

Background: Mivazerol is a new and selective aa-adrenergic receptor ag onist devoid of hypotensive effects (1, 2). Previous studies have demo nstrated that mivazerol prevents hemodynamic instability during emerge nce from halothane anesthesia in rats (3). The present study was to de termine whether glutamate and aspartate are involved in this action of mivazerol, at the second to third thoracic segments (T2-T3) of the sp inal cord. Methods: In vivo microdialysis in combination with high-per formance liquid chromatography (HPLC) was employed in the study. Blood pressure (BP) and heart rate (HR) were recorded along with intratheca l (i.t.) microdialysis perfusion. Results: BP, HR and i.t, release of glutamate (GLU, pmol/mu l) were stable in the rats under 1.1% halothan e anesthesia. How ever, halothane withdrawal immediately increased BP, I-IR, and i.t. release of GLU, and remained elevated for at least 2 h after withdrawal of halothane. Thirty minutes prior to halothane with drawal, intravenous (i.v.) infusion of mivazerol (15 mu g . kg(-1) . h (-1)) almost completely prevented the increases in HR (Delta 18+/-7 vs Delta 79+/-7 beats/min), and in the i.t, release of GLU (Delta 10.3+/ -3.7 vs Delta 30.6+/-5.9; 112% vs 167%). Local i.t, microinjection of mivazerol (2.5 mu g/kg) 2 min prior to withdrawal of halothane also bl ocked the HR responses, as well as on the i.t. release of GLU followin g halothane withdrawal. Conclusion: The present study demonstrates tha t emergence from halothane anesthesia increases i.t, release of GLU, a nd that mivazerol has an inhibitory effect on the above, through its d irect action on the spinal cord.