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

Abstract

BACKGROUND:

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.

• Authors: X Zhang, E Wülfert, I Hanin
• Journal: Acta anaesthesiologica Scandinavica (Acta Anaesthesiol Scand) Vol. 41 Issue 6 Pg. 694-700 (Jun 1997) ISSN: 0001-5172 [Print] England
• PMID: 9241327 (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)