title: Plasma cortisol response to ACTH challenge in hypoxic newborn piglets resuscitated with 21% and 100% oxygen.
abstract: Although the use of supplemental oxygen to resuscitate asphyxiated neonates remains controversial, the effects of hypoxia and reoxygenation (room air versus pure oxygen) on the hypothalamo-pituitary-adrenal axis are unknown. We aimed to evaluate the effect of hypoxia and reoxygenation with either 21% or 100% oxygen on plasma cortisol before and after an adrenocorticotrophin (ACTH) challenge in newborn piglets. Thirty-five piglets (aged 1-3 days, weighing 1.5-2.4 kg) were instrumented to measure heart rate, MAP, and cardiac output. After 2 h of normocapnic hypoxia (PaO2, 20-30 mmHg; pH, <6.95), piglets were resuscitated with 21% or 100% oxygen for 1 h and then 21% oxygen for 3 h. Sham-operated piglets had no hypoxia-reoxygenation (H-R). Serial plasma cortisol levels were determined after a blinded randomized administration of ACTH (4 microg/kg, i.v.) or saline at 2 h reoxygenation. The expression of steroidogenic factor 1 in the adrenals was studied. Cardiac output decreased with hypoxia and recovered with resuscitation. Piglets developed hypotension similarly in 21% and 100% H-R groups during reoxygenation (versus sham-operated group, P < 0.05). Both H-R groups had increased plasma cortisol levels (versus sham-operated group, P < 0.05) at 2 h of reoxygenation after hypoxia, with a further increase in levels in 21% H-R piglets at 4 h reoxygenation (versus 100% H-R piglets, P < 0.05). The response to ACTH was delayed in H-R groups, with the maximum increase at 120 min post-ACTH administration (versus 30-60 min post-ACTH for sham-operated piglets). Plasma cortisol levels increased significantly post-ACTH administration in 21% H-R and sham-operated piglets (115% +/-50% and 126% +/- 25% at 120 min, respectively, P < 0.05 vs. pre-ACTH baselines) but not in 100% H-R piglets (51% +/-14%), which had a lower expression of steroidogenic factor 1 than the other groups. Although the clinical significance of high cortisol levels and cortisol response to ACTH in H-R newborn piglets is uncertain, a preserved cortisol response may support using room air in neonatal resuscitation.
authors.affiliation: Departments of Paediatrics and Medicine, University of Alberta, Calgary, Alberta, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chapados
authors.forename: Constance L
authors.initials: CL
authors.lastname: Chik
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000324:Adrenocorticotropic Hormone; D000818:Animals; D000831:Animals, Newborn; D002302:Cardiac Output; D006854:Hydrocortisone / Q000097:blood*; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D023421:Models, Animal; D010100:Oxygen / Q000008:administration & dosage / Q000627:therapeutic use*; D044103:Receptor, Melanocortin, Type 2 / Q000096:biosynthesis; D012151:Resuscitation / Q000379:methods; D012770:Shock, Cardiogenic / Q000097:blood / Q000188:drug therapy; D054339:Steroidogenic Factor 1; D013552:Swine
chemical_list: D044103:Receptor, Melanocortin, Type 2; D054339:Steroidogenic Factor 1; D000324:Adrenocorticotropic Hormone; D010100:Oxygen; D006854:Hydrocortisone