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Mivazerol, a new alpha 2-adrenergic agonist, blunts cardiovascular effects following surgical stress in pentobarbital-anesthetized rats.

AbstractBACKGROUND:
Mivazerol is a new and selective alpha 2-adrenoceptor agonist, devoid of hypotensive effects, which has been designed to prevent adverse cardiac outcome in perioperative patients with, or at risk coronary artery disease.
METHODS:
In the present study, the effects of mivazerol on hemodynamic changes induced by trachea-exposure surgery stress were investigated in pentobarbital-anesthetized rats, and compared to those of dexmedetomidine.
RESULTS:
Intravenous infusion of 3 different doses of mivazerol (3.75, 7.5 and 15 micrograms.kg-1.h-1) did not significantly alter BP but caused a dose-related decrease in HR. The maximal decrease in HR was approximately 87 beats/min. Contrary to mivazerol, dexmedetomidine (7.5 micrograms.kg-1.h-1, i.v.) decreased both BP (11 +/- 3.2 mmHg) and HR. The maximum decrease in HR was approximately 104 beats/min. Surgical stress produced a rapid increase in BP (maximal increase of 50 mmHg) and HR (maximal increase of 100 beats/min), which lasted for at least 15 min. Constant infusion of mivazerol, at dose of 15 micrograms.kg-1.h-1, beginning 20 min prior to surgery and lasting for 35 min, significantly inhibited surgical stress-induced increases in BP (P < 0.05) and HR (P < 0.001). Dexmedetomidine, at a dose which produced hypotension and profound bradycardia prior to surgery, did not have any effect on the surgical stress-induced elevation in BP (P > 0.05), but prevented the increase in HR (P < 0.05). Pretreatment with the alpha 2-adrenoceptor antagonist rauwolscine (0.5 mg/kg, i.v.) blocked the bradycardia induced by mivazerol as well as the inhibitory effect of mivazerol on surgical stress-induced elevations in HR and BP.
CONCLUSION:
Mivazerol attenuates surgical stress-induced elevations in BP and HR during pentobarbital anesthesia in rats, and these effects are mediated by stimulation of alpha 2-adrenoceptors. Unlike dexmedetomidine, mivazerol does not reduce BP, and is also more potent than dexmedetomidine in blunting surgical stress-induced increases in BP in pentobarbital-anesthetized rats.
AuthorsX Zhang, E Wülfert, I Hanin
JournalActa anaesthesiologica Scandinavica (Acta Anaesthesiol Scand) Vol. 41 Issue 6 Pg. 694-700 (Jun 1997) ISSN: 0001-5172 [Print] DENMARK
PMID9241327 (Publication Type: Journal Article)
Chemical References
  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Imidazoles
  • Yohimbine
  • Pentobarbital
  • Clonidine
  • Medetomidine
  • mivazerol
Topics
  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-Agonists (pharmacology)
  • Anesthesia
  • Animals
  • Blood Pressure (drug effects)
  • Clonidine (pharmacology)
  • Heart Rate (drug effects)
  • Imidazoles (pharmacology)
  • Medetomidine
  • Pentobarbital (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological (physiopathology)
  • Surgical Procedures, Operative
  • Yohimbine (pharmacology)

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