title: Oral dexmedetomidine preserves baroreceptor function and decreases anesthetic requirements of halothane-anesthetized dogs.
abstract: BACKGROUND
  The alpha 2-adrenergic agonist, dexmedetomidine, alters hemodynamics by diminishing sympathetic and/or augmenting parasympathetic neurogenic tone to the heart and peripheral vasculature. However, the specific actions of dexmedetomidine on baroreceptor function are unknown. The purpose of the current investigation was to determine baroreceptor function during an anesthetic state produced by halothane and a similar anesthetic state produced by halothane after dexmedetomidine pretreatment.
  
  
  METHODS
  Dogs were instrumented for measurement of arterial and left ventricular pressures, coronary blood flow velocity, segment shortening and cardiac output. Five experimental conditions were studied in the same dogs (n = 8). Measurements of baroreceptor sensitivity (via abrupt decreases and increases in arterial pressure resulting in changes in the cardiac cycle) and hemodynamics were made in the conscious state in dogs in conditions 1 and 2 before and after 25 and 50 micrograms.kg-1 of oral dexmedetomidine, respectively. Dogs in conditions 3 and 4 received the same doses of dexmedetomidine and were then anesthetized with halothane. Baroreceptor sensitivity was determined after 60 min of halothane anesthesia. For comparison, dogs in condition 5 had baroreceptor sensitivity measured after 60 min of halothane anesthesia in the absence of dexmedetomidine.
  
  
  RESULTS
  Dexmedetomidine decreased heart rate, rate-pressure product, rate of increase of left ventricular pressure at 50 mmHg, cardiac output and percent segment shortening. Diastolic coronary vascular resistance and systemic vascular resistance were increased with both oral doses. In addition, diastolic coronary blood flow velocity and stroke volume were significantly reduced by the high dose of dexmedetomidine. Anesthesia with halothane increased heart rate and decreased mean arterial pressure, left ventricular systolic pressure, rate of increase of left ventricular pressure at 50 mmHg, stroke volume and segment shortening. Administration of dexmedetomidine before halothane anesthesia in dogs pretreated with dexmedetomidine resulted in small increases in heart rate and decreases mean arterial pressure and left ventricular systolic pressure. Both doses of dexmedetomidine demonstrated anesthetic-sparing effects. The end-tidal concentration of halothane to maintain dogs unconscious and unresponsive was reduced by 30% and 40% (1.03 +/- 0.08% to 0.67 +/- 0.09% and to 0.58 +/- 0.06% end-tidal, respectively) at 25 and 50 micrograms.kg-1, respectively. Baroreceptor sensitivity was profoundly depressed by halothane alone. Dexmedetomidine did not significantly change the slope of the baroreflex response when compared with conscious control measurements. After pretreatment with dexmedetomidine, the reduction in halothane concentration required for a comparable level of anesthesia resulted in significant preservation of baroreceptor sensitivity.
  
  
  CONCLUSIONS
  The results indicate that dexmedetomidine alone does not alter baroreflex sensitivity. In addition, possibly through an anesthetic-sparing action, dexmedetomidine preserves baroreflex responses during halothane anesthesia. Such a preservation of the baroreceptor reflex by dexmedetomidine might provide an important mechanism for maintenance of cardiovascular stability by retaining buffer reflexes during general anesthesia.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
authors.forename: A
authors.initials: A
authors.lastname: Devcic
authors.forename: W T
authors.initials: WT
authors.lastname: Schmeling
authors.forename: J P
authors.initials: JP
authors.lastname: Kampine
authors.forename: D C
authors.initials: DC
authors.lastname: Warltier
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D006221:Halothane / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D020926:Medetomidine; D011292:Premedication; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology*
chemical_list: D007093:Imidazoles; D020926:Medetomidine; D006221:Halothane