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


CONCLUSIONS
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.
Zhang
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X
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, USA.
Wülfert
E
E
Hanin
I
I
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D020926:Medetomidine; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*; D013514:Surgical Procedures, Operative; D015016:Yohimbine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D015016:Yohimbine; D010424:Pentobarbital; D003000:Clonidine; D020926:Medetomidine; C087969:mivazerol