Simulated acute hemorrhage through lower body negative pressure as an activator of the hypothalamic-pituitary-adrenal axis.
While insulin induced hypoglycemia is the principle method of producing hypothalamic-pituitary-adrenal stress response, the mechanism by which this occurs may be different from that produced by other stressors. In a pilot study, we explored ways to standardize lower body negative pressure (LBNP), as a simulator of hemorrhage, to determine its utility for future studies of hypothalamic-pituitary-adrenal (HPA) axis function. Reduced atmospheric pressure of -40 mmHg applied at the level of the iliac crests during LBNP rapidly lowers blood pressure in most subjects, simulating acute hemorrhage. In 6 normal subjects, ACTH and cortisol values were measured before, during and after the application LBNP at 0800, 1600 and 2300 hours in the baseline state and at 1600 hours on the day following 1 mg of dexamethasone. Peak ACTH values of 60-250 pg/ml occurred 2 to 10 minutes after the cessation of the stimulus in subjects experiencing presyncope or having a systolic or diastolic blood pressure decrease of greater than 20 mmHg with a rise in pulse of 30 beats per minute or more. There was no significant difference between ACTH responses at different times of day. Peak cortisol values of 25-30 micrograms/dl occurred 15-20 minutes after cessation of the stimulus. In all subjects, administration of dexamethasone greatly attenuated the ACTH response and decreased but did not ablate the cortisol response. In conclusion, these data indicate that LBNP may be used to simulate hemorrhage as a stimulus of the HPA axis. HPA axis changes occur only when physiologic evidence of hypovolemic stress is present. Dexamethasone may be used to modulate the response to this stress paradigm.
Pitts
A F
AF
Department of Psychiatry and Neuroscience Program, University of Iowa Hospitals, Iowa City.
Preston
M A
MA
Jaeckle
R S
RS
Meller
W
W
Kathol
R G
RG
D000208:Acute Disease; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology; D006439:Hemodynamics; D006470:Hemorrhage / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008150:Lower Body Negative Pressure / Q000295:instrumentation*; D008297:Male; D008954:Models, Biological; D010913:Pituitary-Adrenal System / Q000503:physiopathology*
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone