title: Xenon offers stable haemodynamics independent of induced hypothermia after hypoxia-ischaemia in newborn pigs.
abstract: OBJECTIVE
  To assess the effect of 18 hour (h) 50% xenon (Xe) inhalation at normothermia (NT, 38.5°C) or hypothermia (HT, 33.5°C) on mean arterial blood pressure (MABP), inotropic support and heart rate (HR) following an induced perinatal global hypoxic-ischaemic insult (HI) in newborn pigs.
  
  
  METHODS
  Newborn pigs ventilated under inhalational anaesthesia, following a 45 min HI (inhaled oxygen fraction reduced until amplitude integrated electroencephalogram was less than 7 μV), were randomised to three Xe (n = 45) (50% Xe 18 h with NT, HT 12 h or HT 24 h) or three non-Xe groups (n = 53) (0% Xe with NT, HT 12 h or HT 24 h) under otherwise identical conditions. We measured MABP and HR every minute. Hypotension (MABP <40 mmHg) was treated sequentially with 2 × 10 mL/kg saline, dopamine, norepinephrine and hydrocortisone if required.
  
  
  RESULTS
  Xe maintained higher MABP during HT (5.1 mmHg, 95% CI 2.34, 7.89), rewarming (10.1 mmHg, 95% CI 6.26, 13.95) and after cessation (4.1 mmHg, 95% CI 0.37, 7.84) independent of HT, inotropic support and acidosis. Xe reduced the duration of inotropic support by 12.6 h (95% CI 5.5, 19.73). Inotropic support decreased the HR reduction induced by HT from 9 to 5 bpm/°C during cooling and from 10-7 to 4-3 bpm/°C during rewarming. There was no interaction between Xe, HT, inotropic support and acidosis. Xe during HT cleared lactate faster; 3 h post-HI median (IQR) values of (Xe HT) 2.8 mmol/L (0.9, 3.1) vs. (HT) 5.9 mmol/L (2.5, 7.9), p = 0.0004.
  
  
  CONCLUSIONS
  Xe maintained stable blood pressure, thereby reducing the inotropic support requirements during and after administration independently of induced HT-current neonatal encephalopathy treatment. Xe may offer haemodynamic benefits in clinical neuroprotection studies.
authors.affiliation: Department of Child Health, School of Clinical Sciences, St Michael's Hospital, Level D, University of Bristol, Southwell Street, BS2 8EG Bristol, UK.
authors.forename: Elavazhagan
authors.initials: E
authors.lastname: Chakkarapani
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: Lars
authors.initials: L
authors.lastname: Walloe
authors.forename: John
authors.initials: J
authors.lastname: Dingley
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000517:prevention & control*; D013552:Swine; D014978:Xenon / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D014978:Xenon