title: Cardiopulmonary and behavioral responses to computer-driven infusion of detomidine in standing horses.
abstract: Cardiopulmonary and behavioral responses to detomidine, a potent alpha 2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 2), 19.1 +/- 5.1. (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused concentration-dependent sedation and somnolence. These effects were profound during infusions 3 and 4, in which marked head ptosis developed and all horses leaned heavily on the bars of the restraining stocks. Heart rate and cardiac index decreased from baseline measurements (42 +/- 7 beats/min, 65 +/- 11 ml.kg of body weight-1.min-1) in linear relationship with the logarithm of plasma detomidine concentration (ie, heart rate = -4.7 [loge detomidine concentration] + 44.3, P < 0.01; cardiac index = -10.5 [loge detomidine concentration] + 73.6, P < 0.01). Second-degree atrioventricular block developed in 5 of 7 horses during infusion 3, and in 6 of 7 horses during infusion 4. Mean arterial blood pressure increased significantly from 118 +/- 11 mm of Hg at baseline to 146 +/- 27 mm of Hg at infusion 4. Similar responses were observed for mean pulmonary artery and right atrial pressures. Systemic vascular resistance (baseline, 182 +/- 28 mm of Hg.ml-1.min-1.kg-1) increased significantly during infusions 3 and 4 (to 294 +/- 79 and 380 +/- 58, respectively). (ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, CA 94305.
authors.forename: D A
authors.initials: DA
authors.lastname: Daunt
authors.forename: C I
authors.initials: CI
authors.lastname: Dunlop
authors.forename: P L
authors.initials: PL
authors.lastname: Chapman
authors.forename: S L
authors.initials: SL
authors.lastname: Shafer
authors.forename: H
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: O
authors.initials: O
authors.lastname: Vakkuri
authors.forename: D S
authors.initials: DS
authors.lastname: Hodgson
authors.forename: L M
authors.initials: LM
authors.lastname: Tyler
authors.forename: M
authors.initials: M
authors.lastname: Maze
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D003201:Computers; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006736:Horses / Q000502:physiology*; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial / Q000662:veterinary; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009919:Orchiectomy; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011187:Posture; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000700:Analgesics; D007093:Imidazoles; D002245:Carbon Dioxide; C041255:detomidine; D010100:Oxygen