title: Hemodynamic effects of dexmedetomidine, an alpha 2-adrenergic agonist, in autonomically denervated dogs.
abstract: The hemodynamic effects of the alpha 2-adrenergic agonist, dexmedetomidine (DM), were studied in eight anesthetized, autonomically denervated dogs. Autonomic block decreased mean arterial pressure (MAP) and cardiac index (CI) by approximately 20% to 95 +/- 8 mm Hg and 4.1 +/- 0.1 L/min/m2, respectively (mean +/- SEM), and reduced norepinephrine (NE) and epinephrine plasma levels to almost undetectable levels. DM, administered intravenously (i.v.) either by bolus injection or by slow (20 min) infusion in doses between 1 and 30 micrograms/kg, had no effect on heart rate (HR), increased MAP significantly by 98%, decreased CI by 59%, and increased calculated systemic vascular resistance index (SVRI) significantly by 376%, maximally. The effect of the lowest dose was mediated mainly by arteriolar vasoconstriction, and that of higher doses was mediated by vasoconstriction and decreased CI. Left ventricular end-diastolic pressure (LVEDP) increased significantly from 6 +/- 2 to greater than 30 mm Hg. maximally. The effects were cumulative, and the first dose caused near maximal pressor effect; the resistance increase was as great with slow infusion as with bolus injection. Prazosin (1 mg/kg) did not affect the changes, but 0.3 mg/kg atipamezole, a selective alpha 2-antagonist, completely antagonized them. These observations demonstrate potent constriction of both arteriolar resistance and venous capacitance vasculature in dogs. The combination of decreased CI and increased filling pressure implies marked decrease in cardiac function which was, however, fully reversible by atipamezole.
authors.affiliation: Department of Anesthesiology, UCLA School of Medicine 90024-1778.
authors.forename: J W
authors.initials: JW
authors.lastname: Flacke
authors.forename: W E
authors.initials: WE
authors.lastname: Flacke
authors.forename: B C
authors.initials: BC
authors.lastname: Bloor
authors.forename: D F
authors.initials: DF
authors.lastname: McIntee
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D013562:Sympathectomy
chemical_list: D000318:Adrenergic beta-Agonists; D007093:Imidazoles; D020926:Medetomidine