A novel alpha2-adrenoceptor antagonist attenuates the early, but preserves the late cardiovascular effects of intravenous dexmedetomidine in conscious dogs☆

Objectives: To test the hypothesis that L-659,066, a peripherally acting α2-adrenoceptor agonist, will abolish the early pressor response but preserve the late depressor action of intravenous dexmedetomidine in conscious, unsedated dogs. Design: A prospective investigation. Setting: A laboratory research. Participants: Nine chronically instrumented dogs. Interventions: Dogs received dexmedetomidine, 5 μg/kg intravenously, in the presence or absence of L-659,066, 0.1, 0.2, or 0.4 mg/kg intravenously, pretreatment in a random fashion determined with a Latin square design on different experimental days. Measurements and Main Results: Systemic and coronary hemodynamics were assessed under control conditions, 30 minutes after administration of L-659,066 and 5 and 60 minutes after intravenous administration of dexmedetomidine. Dexmedetomidine alone acutely increased mean arterial pressure (106 ± 3 to 175 ± 4 mmHg; p < 0.05), left ventricular (LV) systolic and end-diastolic pressures, systemic vascular resistance (3,400 ± 350 to 13,360 ± 2,290 dyne · s · cm−5; p < 0.05), and coronary vascular resistance (2.69 ± 0.19 to 4.18 ± 0.43 mmHg · Hz−1. 10−2; p < 0.05) and decreased LV +dP/dtmax and cardiac output (2.6 ± 0.3 to 1.3 ± 0.2 L/min; p < 0.05). Dexmedetomidine alone decreased heart rate, mean arterial pressure, and LV systolic pressure and caused sustained reductions in +dP/dtmax and cardiac output up to 60 minutes after administration. L-659,066 alone increased heart rate, +dP/dtmax, cardiac output, and coronary blood flow velocity and decreased systemic vascular resistance. Mean arterial and LV pressures and coronary vascular resistance were unchanged. Pretreatment with L-659,066 abolished the acute dexmedetomidineinduced increases in mean arterial pressure, LV pressures, systemic and coronary vascular resistance and decreases in +dP/dtmax and cardiac output. In contrast, reductions in mean arterial pressure and LV systolic pressure observed 60 minutes after administration of dexmedetomidine were preserved in dogs receiving L-659,066. Cardiac performance, systemic vascular resistance, and coronary hemodynamics were also maintained to a greater degree 60 minutes after dexmedetomidine administration in the presence of L-659,066. Conclusion: L-659,066 prevents the immediate pressor effects of 5 μg/kg of intravenous dexmedetomidine but preserves the majority of the late beneficial cardiovascular effects of this selective α2-adrenoceptor agonist in conscious dogs.