Effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects.
BACKGROUND
Dexmedetomidine, a selective alpha2-adrenoceptor agonist, has counteracting effects on the cardiovascular system. It mediates sympatholysis by activating alpha2 adrenoceptors in the central and peripheral nervous system, and vasoconstriction and vasorelaxation by activating postsynaptic alpha2 adrenoceptors in blood vessels. The goal of this study was to determine the effects of therapeutic and high concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy subjects.


METHODS
The authors studied 12 healthy young men. Myocardial blood flow (assessed with positron emission tomography), myocardial function (by echocardiography), and hemodynamic data were collected before and during low (measured mean plasma concentration, 0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine.


RESULTS
The low concentration of dexmedetomidine reduced myocardial perfusion (mean difference, -27% from baseline [95% confidence interval, -31 to -23%], P < 0.001) in parallel with a reduction in myocardial oxygen demand (estimated by the rate-pressure product (-23% [-28 to -18%], P < 0.001). The high dexmedetomidine plasma concentration did not further attenuate myocardial perfusion (-3% [-12 to +6%] from low dexmedetomidine, P > 0.05; -29% [-39 to -18%] from baseline, P < 0.001) or statistically significantly affect the rate-pressure product (+5% [0 to +10%], P > 0.05). Systolic myocardial function was attenuated by sympatholysis during the low infusion rate and was further attenuated by a combination of the sustained sympatholysis and increased afterload during the high infusion rate.


CONCLUSIONS
In healthy subjects, plasma concentrations of dexmedetomidine that significantly exceed the recommended therapeutic level do not seriously attenuate myocardial perfusion below the level that is observed with usual therapeutic concentrations and do not induce evident myocardial ischemia.
Snapir
Amir
A
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, FI-20520 Turku, Finland. snapir@utu.fi
Posti
Jussi
J
Kentala
Erkki
E
Koskenvuo
Juha
J
Sundell
Jan
J
Tuunanen
Helena
H
Hakala
Kristo
K
Scheinin
Harry
H
Knuuti
Juhani
J
Scheinin
Mika
M
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D004452:Echocardiography; D004837:Epinephrine / Q000097:blood; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000097:blood; D049268:Positron-Emission Tomography; D014655:Vascular Resistance / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D020927:Dexmedetomidine; D009638:Norepinephrine; D004837:Epinephrine