title: Cardiovascular and parasympathetic effects of dexmedetomidine in healthy subjects.
abstract: We evaluated the cardiovascular effects of intravenously (i.v.) and buccally administered dexmedetomidine, a selective alpha2-adrenoceptor agonist. Six healthy male subjects were studied unmedicated and after 2 micro g/kg i.v. or buccal doses of dexmedetomidine, using repeated recordings of ECG and blood pressure. Cardiac parasympathetic activity was estimated by measurements of high-frequency (HF) heart rate variability. Intravenous, but not buccal, dexmedetomidine raised systolic blood pressure by 11 +/- 5 mmHg (mean +/- SEM) and diastolic by 16 +/- 3 mmHg (maxima at 10 min). Later on, both i.v., and buccal dexmedetomidine produced a very similar hypotensive effect: on average, >or=10 mmHg reductions in systolic and diastolic pressure at 3 h. Intravenous dosing was followed by a decline in heart rate (-11 +/- 2 beats/min) accompanied by a trend toward enhanced HF variability (maximal effect at 10 min), which probably reflected baroreflex-mediated parasympathetic efferent neuronal activation. Buccal dexmedetomidine increased significantly the HF variability (maximum at 45 min) without influencing heart rate. We conclude that dexmedetomidine, when administered by a method that avoids concentration peaks, e.g., buccal dosing, can be used to produce a prolonged augmentation of cardiac parasympathetic efferent neuronal activity.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Penttilä
authors.forename: Antti
authors.initials: A
authors.lastname: Helminen
authors.forename: Markku
authors.initials: M
authors.lastname: Anttila
authors.forename: Susanna
authors.initials: S
authors.lastname: Hinkka
authors.forename: Harry
authors.initials: H
authors.lastname: Scheinin
mesh_terms: D000278:Administration, Buccal; D000328:Adult; D000704:Analysis of Variance; D002319:Cardiovascular System / Q000187:drug effects*; D020927:Dexmedetomidine / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D020927:Dexmedetomidine