MIVAZEROL PREVENTS THE TACHYCARDIA CAUSED BY EMERGENCE FROM HALOTHANEANESTHESIA PARTLY THROUGH ACTIVATION OF SPINAL ALPHA(2)-ADRENOCEPTORS

Background: Mivazerol (MIV) is an alpha(2)-adrenoceptor agonist design ed to prevent adverse cardiac outcome in perioperative patients. The p resent study was undertaken to determine whether the hyperdynamic stat e observed at emergence from halothane (HAL) anesthesia in rats could be modulated by MIV and to explore the mode of action of MN under such conditions. Methods: Male Sprague Dawley rats were anesthetized with 1% HAL and assisted for respiration (N2O-O-2: 70-30%). MIV 2.2-15.3 mu g.kg(-1).h(-1) i.v. was infused 30 min before withdrawal of anesthesi a and compared for heart rate (HR) and systolic arterial blood pressur e (SAP) to control animals treated with saline. In some experiments, a nimals were pretreated with intrathecal pertussis toxin (T2 level, 0.5 mu g, 7 d), or i.v. rauwolscine (0.34 mg/kg, 5 min) or were bilateral ly stellectomized (30 min) prior to withdrawal of HAL. Results: Increa ses in HR (65 bpm, +20%) and in SAP (25 mmHg, +26%) were observed imme diately upon discontinuation of HAL and remained constant for at least 30 min. The increase in HR was abolished by removal of the stellate g anglia. MIV dose-dependent inhibited the increase in HR from 4.8 mu g. kg(-1).h(-1) (68% reduction, P < 0.05) without affecting HR or SAP dur ing anesthesia. Inhibition of HR increase was of 98% at 15.3 mu g.kg(- 1).h(-1). This effect was abolished by rauwolscine, and partially (50% ) inhibited by pertussis toxin pre-treatment. Conclusion: These result s demonstrate that withdrawal of HAL anesthesia in the rat produces a sustained increase in HR due to activation of the sympathetic system a nd that MIV inhibits this tachycardia via activation of alpha(2)-aadre noeeptors located at least in part in the spinal cord.