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 ago nist, devoid of hypotensive effects, which has been designed to preven t adverse cardiac outcome in perioperative patients with, or at risk o f coronary artery disease. Methods: In the present study, the effects of mivazerol on hemodynamic changes induced by trachea-exposure surger y stress were investigated In pentobarbital-anesthetized rats, and com pared to those of dexmedetomidine. Results: Intravenous infusion of 3 different doses of mivazerol (3.75, 7.5 and 15 mu g . kg(-1) . h-1) di d not significantly alter BP but caused a dose-related decrease in HR. The maximal decrease in HR was approximately 87 beats/min. Contrary t o mivazerol, dexmedetomidine (7.5 pg . kg(-1) . h(-1), i.v.) decreased both BP (11+/-3.2 mmHg) and HR. The maximum decrease in HR was approx imately 104 beats/min. Surgical stress produced a rapid increase in BP (maximal increase of 50 mmHg) and HR (maximal increase of 100 beats/m in), which lasted for at least 15 min. Constant infusion of mivazerol, at a dose of 15 mu g . kg(-1) . h(-1) beginning 20 min prior to surge ry and lasting for 35 min, significantly inhibited surgical stress-ind uced increases in (P<0.05) and HR (P<0.001). Dexmedetomidine, at a dos e 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 w ith the alpha(2)-adrenoceptor antagonist rauwolscine (0.5 mg/kg, i.v.) blocked the bradycardia induced by mivazerol as well as the inhibitor y effect of mivazerol on surgical stress-induced elevations in HR and BP. Conclusion: Mivazerol attenuates surgical stress-induced elevation s in BP and HR during pentobarbital anesthesia in rats, and these effe cts are mediated by stimulation of alpha(2)-adrenoceptors. Unlike dexm edetomidine, mivazerol does not reduce BP, and is also more potent tha n dexmedetomidine in blunting surgical stress-induced increases in BP in pentobarbital-anesthetized rats.