title: Evaluation of histamine release during constant rate infusion of morphine in dogs.
abstract: OBJECTIVE
  To evaluate histamine release and selected physiologic variables during constant rate infusion (CRI) of morphine in dogs.
  
  
  METHODS
  Five healthy, conscious, intact female dogs.
  
  
  METHODS
  Using a Latin square, repeated-measures design, dogs were randomly assigned to three treatment groups to receive a 4-hour CRI of saline (SAL), or a loading dose of morphine at 0.3 mg kg(-1) (LM), or 0.6 mg kg(-1) (HM), followed by an infusion of 0.17 mg kg(-1) hour(-1) (LM) and 0.34 mg kg(-1) hour(-1) (HM) respectively. Dogs received each of the three treatments at intervals of at least 7 days. Plasma histamine concentration, skin flushing, edema and wheals, heart rate and rhythm and non-invasive arterial blood pressure were measured before the loading dose and at 1, 2, 5, 15, 30, 60, 120, 180 and 240 minutes during the CRI, or at the time of occurrence.
  
  
  RESULTS
  The loading dose induced the highest histamine release in the HM group being statistically higher than the SAL group. The histamine release obtained in the LM group after the loading dose did not differ from SAL. During the infusion, plasma histamine levels were numerically higher in the LM group. Besides one dog that developed hypotension for 2 minutes after the loading dose in the HM group and one dog that showed occasional ventricular premature contractions during both morphine infusions, cardiovascular variables were similar among the three treatment groups.
  
  
  CONCLUSIONS
  Both doses of morphine induced variable histamine release with minimal adverse cardiovascular effects in these conscious, healthy dogs. The plasma histamine levels obtained may be associated with significant hemodynamic changes in patients with limited cardiovascular reserve and sympathetic nervous tone.
authors.affiliation: Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108-1016, USA. guede003@umn.edu
authors.forename: Alonso G P
authors.initials: AG
authors.lastname: Guedes
authors.forename: Elaine P
authors.initials: EP
authors.lastname: Rudé
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rider
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects*; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D009020:Morphine