title: Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure.
abstract: BACKGROUND
  A reduced oxygen supply puts patients at risk of tissue hypoxia, organ damage, and even death. In response, several changes are activated that allow for at least partial adaptation, thereby increasing the chances of survival. We aimed to investigate whether the arginine vasopressin marker, copeptin, can be used as a marker of the degree of acclimatization/adaptation in rats exposed to hypoxia.
  
  
  METHODS
  Sprague-Dawley rats were exposed to 10% oxygen for up to 48 hours. Arterial and right ventricular pressures were measured, and blood gas analysis was performed at set time points. Pulmonary changes were investigated by bronchoalveolar lavage, wet and dry weight measurements, and lung histology. Using a newly developed specific rat copeptin luminescence immunoassay, the regulation of vasopressin in response to hypoxia was studied, as was atrial natriuretic peptide (ANP) by detecting mid-regional proANP.
  
  
  RESULTS
  With a decreasing oxygen supply, the rats rapidly became cyanotic and inactive. Despite continued exposure to 10% oxygen, all animals recuperated within 16 hours and ultimately survived. Their systemic blood pressure fell with acute (5 minutes) hypoxia but was partially recovered over time. In contrast, right ventricular pressures increased with acute (5 minutes) hypoxia and normalized after 16 hours. No signs of pulmonary inflammation or edema were found despite prolonged hypoxia. Whereas copeptin levels increased significantly after acute (5 minutes) hypoxia and then returned to near baseline after 16 hours, mid-regional proANP levels were even further increased after 16 hours of exposure to hypoxia.
  
  
  CONCLUSIONS
  Plasma copeptin is a sensitive marker of acute (5 minutes) exposure to severe hypoxia, and subsequent regulation can indicate recovery. Copeptin levels can therefore reflect clinical and physiological changes in response to hypoxia and indicate recovery from ongoing hypoxic exposure.
authors: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich; Zürich Center for Integrative Human Physiology.
authors: Louise
authors: L
authors: Ostergaard
authors: Institute of Anesthesiology.
authors: Alain
authors: A
authors: Rudiger
authors: Zürich Center for Integrative Human Physiology; Division of Neonatology, University Hospital Zürich, Zürich; Department of Neonatology, University Children's Hospital Basel, Basel, Switzerland.
authors: Sven
authors: S
authors: Wellmann
authors: Department of Human Morphology and Biomedical Science, University of Milan, Milan, Italy.
authors: Elena
authors: E
authors: Gammella
authors: Zürich Center for Integrative Human Physiology; Institute of Anesthesiology.
authors: Beatrice
authors: B
authors: Beck-Schimmer
authors: Research Department, B⋅R⋅A⋅H⋅M⋅S Biomarkers, Thermo Fisher Scientific, Hennigsdorf, Germany.
authors: Joachim
authors: J
authors: Struck
authors: Zürich Center for Integrative Human Physiology; Medical Intensive Care Unit, University Hospital Zürich, Zürich, Switzerland.
authors: Marco
authors: M
authors: Maggiorini
authors: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich; Zürich Center for Integrative Human Physiology; Universidad Peruana Cayetano Heredia, Lima, Peru.
authors: Max
authors: M
authors: Gassmann
keywords: acclimatization; adaptation; atrial natriuretic peptide; copeptin; critical illness; hypoxia; vasoactive peptides