A novel alpha 2-adrenoceptor antagonist attenuates the early, but preserves the late cardiovascular effects of intravenous dexmedetomidine in conscious dogs.
OBJECTIVE
To test the hypothesis that L-659,066, a peripherally acting alpha 2-adrenoceptor agonist, will abolish the early pressor response but preserve the late depressor action of intravenous dexmedetomidine in conscious, unsedated dogs.


METHODS
A prospective investigation.


METHODS
A laboratory research.


METHODS
Nine chronically instrumented dogs.


METHODS
Dogs received dexmedetomidine, 5 micrograms/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.


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 dexmedetomidine-induced 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.


CONCLUSIONS
L-659,066 prevents the immediate pressor effects of 5 micrograms/kg of intravenous dexmedetomidine but preserves the majority of the late beneficial cardiovascular effects of this selective alpha 2-adrenoceptor agonist in conscious dogs.
Pagel
P S
PS
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Proctor
L T
LT
Devcic
A
A
Hettrick
D A
DA
Kersten
J R
JR
Tessmer
J P
JP
Farber
N E
NE
Schmeling
W T
WT
Warltier
D C
DC
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003243:Consciousness; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D020926:Medetomidine; D011446:Prospective Studies; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D011807:Quinolizines; D014662:Vasoconstrictor Agents; C055732:vatinoxan; D020926:Medetomidine