A NOVEL ALPHA(2)-ADRENOCEPTOR ANTAGONIST ATTENUATES THE EARLY, BUT PRESERVES THE LATE CARDIOVASCULAR EFFECTS OF INTRAVENOUS DEXMEDETOMIDINEIN CONSCIOUS DOGS

Objectives:To test the hypothesis that L-659,066, a peripherally actin g alpha(2)-adrenoceptor agonist, will abolish the early presser respon se but preserve the late depressor action of intravenous dexmedetomidi ne in conscious, unsedated dogs. Design: A prospective investigation. Setting: A laboratory research. Participants: Nine chronically instrum ented dogs. Interventions: Dogs received dexmedetomidine, 5 mu g/kg in travenously, 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 an d 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 e nd-diastolic pressures, systemic vascular resistance (3,400 +/- 350 to 13,360 +/- 2,290 dyne.s.cm(-5); p < 0.05), and coronary vascular resi stance (2.69 +/- 0.19 to 4.18 +/- 0.43 mmHg.Hz(-1.)10(-2); p < 0.05) a nd decreased LV +dP/dt(max) and cardiac output (2.6 +/- 0.3 to 1.3 +/- 0.2 L/min; p < 0.05). Dexmedetomidine alone decreased heart rate, mea n arterial pressure, and LV systolic pressure and caused sustained red uctions in +dP/dt(max) and cardiac output up to 60 minutes after admin istration. L-659,066 alone increased heart rate, +dP/dt(max), cardiac output, and coronary blood flow velocity and decreased systemic Vascul ar resistance. Mean arterial and LV pressures and coronary vascular re sistance were unchanged. Pretreatment with L-659,066 abolished the acu te dexmedetomidine-induced increases in mean arterial pressure, LV pre ssures, systemic and coronary vascular resistance and decreases in +dP /dt(max) and cardiac output. in contrast, reductions in mean arterial pressure and LV systolic pressure observed 60 minutes after administra tion of dexmedetomidine were preserved in dogs receiving L-659,066. Ca rdiac performance, systemic vascular resistance, and coronary hemodyna mics were also maintained to a greater degree 60 minutes after dexmede tomidine administration in the presence of L-659,066. Conclusion: L-65 9,066 prevents the immediate presser effects of 5 mu g/kg of intraveno us dexmedetomidine but preserves the majority of the late beneficial c ardiovascular effects of this selective alpha(2)-adrenoceptor agonist in conscious dogs. Copyright (C) 1998 by W.B. Saunders Company.