HORMONAL AND HEMODYNAMIC-CHANGES IN A VALIDATED ANIMAL-MODEL OF BRAIN-DEATH

Objective: To examine the hormonal and hemodynamic changes in a valida ted animal model of brain death. Design: Prospective, controlled study . Setting: Experimental research laboratory. Subjects: Adult male mong rel dogs (n = 10). Interventions: Brain death was induced by inflation of a subdural balloon in ten mongrel dogs weighing 23 to 30 kg and va lidated neuropathologically, The hearts were instrumented with microma nometers and ultrasonic flow probes to measure cardiovascular changes. No inotropic or vasoactive support was given, Hemodynamic stability w as maintained with intravenous fluids, Blood samples and hemodynamic r eadings were collected before and after the induction of brain death. Measurements and Main Results: A Gushing reflex, followed by a hyperdy namic response and diabetes insipidus, occurred in every animal follow ing brain death, Mean arterial pressure, heart rate, contractility, an d cardiac output increased to >350 mm Hg, 230 beats/min, 4200 mm Hg/se c, and 2.8 L/min, respectively, at the peak of this phenomenon before returning to baseline. A plasma catecholamine surge was observed in ev ery animal 15 mins after brain death, while the circulating concentrat ions of the pituitary gland hormones vasopressin and adrenocorticotrop hic hormone decreased significantly after 15 and 45 mins of brain deat h, 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 mu g/dL, and 49.7 +/- 9.1 pg/mL, respectively, to 0.34 +/- 0.03 ng/ mL, 1.14 +/- 1.14 mu g/dL, and 6.9 +/- 1.4 pg/mL, respectively, 420 mi ns after brain death. The hematocrit increased significantly 15 mins a fter 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 stre ss hormones, as well as hemodynamic instability, occurred after brain death. Measurements of plasma adrenocorticotrophic hormone and vasopre ssin Values may be useful as diagnostic predictors of brain death, Fur thermore, the observed changes may contribute to organ dysfunction aft er brain death and may necessitate hormonal as well as inotropic and v asoactive support to maintain donor organ function in the clinical set ting.