title: Dexmedetomidine and haemodynamic responses to acute central hypovolaemia in conscious rabbits.
abstract: 1. Effects of the alpha2-adrenoceptor agonist dexmedetomidine on vasoconstrictor and heart rate (HR) responses to acute central hypovolaemia were studied in eight chronically instrumented rabbits. We compared intravenous (i.v.) and fourth ventricular (V4) dexmedetomidine (0.1-10 microg/kg) and the reversal of effects by the alpha2-adrenoceptor antagonist idazoxan and the opioid agonist alfentanil. 2. Gradual inflation of an inferior vena cava (IVC) cuff reduced cardiac index (CI) by 8%/min, with progressive vasoconstriction and increased HR. In control rabbits, at approximately 40% baseline CI, there was sudden decompensation with failure of vasoconstriction and a fall in mean arterial pressure (MAP). 3. Dexmedetomidine (i.v. and V4) reduced resting MAP and HR and caused an earlier decompensation during central hypovolaemia. Intravenous dexmedetomidine (3 and 10 microg/kg) also reduced the slope of the initial vasoconstrictor response and the maximum HR. 4. The effects of dexmedetomidine were reversed by the antagonist idazoxan, which prevented the decompensation phase. Intravenous alfentanil was also effective in restoring the vasoconstrictor response and delaying decompensation with hypovolaemia after dexmedetomidine. Combining dexmedetomidine with an opioid, such as alfentanil, may provide the benefit of reduced sympathetic tone without increased risk of cardiovascular collapse.
authors.affiliation: Department of Pharmacology, University of Melbourne Parkville, Victoria, Australia. d.blake@pharmacology.unimelb.edu.au
authors.forename: D W
authors.initials: DW
authors.lastname: Blake
authors.forename: J
authors.initials: J
authors.lastname: Ludbrook
authors.forename: A F
authors.initials: AF
authors.lastname: Van Leeuwen
mesh_terms: D000208:Acute Disease; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D015760:Alfentanil / Q000008:administration & dosage; D000818:Animals; D001783:Blood Flow Velocity; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006470:Hemorrhage / Q000503:physiopathology*; D019329:Idazoxan / Q000494:pharmacology; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D011311:Pressoreceptors / Q000187:drug effects; D011817:Rabbits; D012769:Shock / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014682:Vena Cava, Inferior / Q000503:physiopathology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D015760:Alfentanil; D020927:Dexmedetomidine; D019329:Idazoxan