Mivazerol prevents the tachycardia caused by emergence from halothane anesthesia partly through activation of spinal alpha 2-adrenoceptors.
BACKGROUND
Mivazerol (MIV) is an alpha 2-adrenoceptor agonist designed to prevent adverse cardiac outcome in perioperative patients. The present study was undertaken to determine whether the hyperdynamic state observed at emergence from halothane (HAL) anesthesia in rats could be modulated by MIV and to explore the mode of action of MIV under such conditions.


METHODS
Male Sprague Dawley rats were anesthetized with 1% HAL and assisted for respiration (N2O-O2: 70-30%). MIV 2.2-15.3 micrograms.kg-1.h-1 i.v. was infused 30 min before withdrawal of anesthesia and compared for heart rate (HR) and systolic arterial blood pressure (SAP) to control animals treated with saline. In some experiments, animals were pretreated with intrathecal pertussis toxin (T2 level, 0.5 microgram, 7 d), or i.v. rauwolscine (0.34 mg/kg, 5 min) or were bilaterally stellectomized (30 min) prior to withdrawal of HAL.


RESULTS
Increases in HR (65 bpm, +20%) and in SAP (25 mmHg, +26%) were observed immediately upon discontinuation of HAL and remained constant for at least 30 min. The increase in HR was abolished by removal of the stellate ganglia. MIV dose-dependently inhibited the increase in HR from 4.8 micrograms.kg-1.h-1 (68% reduction, P < 0.05) without affecting HR or SAP during anesthesia. Inhibition of HR increase was of 98% at 15.3 micrograms.kg-1.h-1. This effect was abolished by rauwolscine, and partially (50%) inhibited by pertussis toxin pre-treatment.


CONCLUSIONS
These results demonstrate that withdrawal of HAL anesthesia in the rat produces a sustained increase in HR due to activation of the sympathetic system and that MIV inhibits this tachycardia via activation of alpha 2-adrenoceptors located at least in part in the spinal cord.
Guyaux
M
M
UCB S.A., Pharmaceutical Sector, Chemin du Foriest, Belgium.
Gobert
J
J
Noyer
M
M
Vandevelde
M
M
Wülfert
E
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D006221:Halothane / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018685:Anesthetics, Inhalation; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D006221:Halothane; C087969:mivazerol