title: Hormonal and hemodynamic changes in a validated animal model of brain death.
abstract: OBJECTIVE
  To examine the hormonal and hemodynamic changes in a validated animal model of brain death.
  
  
  METHODS
  Prospective, controlled study.
  
  
  METHODS
  Experimental research laboratory.
  
  
  METHODS
  Adult male mongrel dogs (n = 10).
  
  
  METHODS
  Brain death was induced by inflation of a subdural balloon in ten mongrel dogs weighing 23 to 30 kg and validated neuropathologically. The hearts were instrumented with micromanometers and ultrasonic flow probes to measure cardiovascular changes. No inotropic or vasoactive support was given. Hemodynamic stability was maintained with intravenous fluids. Blood samples and hemodynamic readings were collected before and after the induction of brain death.
  
  
  RESULTS
  A Cushing reflex, followed by a hyperdynamic response and diabetes insipidus, occurred in every animal following brain death. Mean arterial pressure, heart rate, contractility, and cardiac output increased to > 350 mm Hg, 230 beats/min, 4200 mm Hg/sec, and 2.8 L/min, respectively, at the peak of this phenomenon before returning to baseline. A plasma catecholamine surge was observed in every animal 15 mins after brain death, while the circulating concentrations of the pituitary gland hormones vasopressin and adrenocorticotrophic hormone decreased significantly after 15 and 45 mins of brain death, respectively, and continued to decrease throughout the experiments. Circulating triiodothyronine, thyroxine, and glucagon concentrations decreased significantly (p < .01) from 0.58 +/- 0.05 ng/mL, 2.20 +/- 0.15 micrograms/dL, and 49.7 +/- 9.1 pg/mL, respectively, to 0.34 +/- 0.03 ng/mL, 1.14 +/- 1.14 micrograms/dL, and 6.9 +/- 1.4 pg/mL, respectively, 420 mins after brain death. The hematocrit increased significantly 15 mins after brain death and then gradually decreased throughout the duration of the experiments.
  
  
  CONCLUSIONS
  In a validated animal model of brain death, significant decreases in the circulating concentrations of stress hormones, as well as hemodynamic instability, occurred after brain death. Measurements of plasma adrenocorticotrophic hormone and vasopressin values may be useful as diagnostic predictors of brain death. Furthermore, the observed changes may contribute to organ dysfunction after brain death and may necessitate hormonal as well as inotropic and vasoactive support to maintain donor organ function in the clinical setting.
authors.affiliation: Department of General and Cardiothoracic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Chen
authors.forename: H B
authors.initials: HB
authors.lastname: Bittner
authors.forename: S W
authors.initials: SW
authors.lastname: Kendall
authors.forename: P
authors.initials: P
authors.lastname: Van Trigt
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001926:Brain Death / Q000097:blood / Q000503:physiopathology*; D002395:Catecholamines / Q000097:blood*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005934:Glucagon / Q000097:blood; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000473:pathology; D011446:Prospective Studies; D014667:Vasopressins / Q000097:blood*
chemical_list: D002395:Catecholamines; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D005934:Glucagon