Rønnaug Solberg1, Julia Kuligowski2, Leonid Pankratov1, Javier Escobar2, Guillermo Quintás3, Isabel Lliso2, Ángel Sánchez-Illana2, Ola Didrik Saugstad1, Máximo Vento2,4. 1. Department of Pediatric Research, Institute for Surgical Research, University of Oslo, Oslo University Hospital - Rikshospitalet, Oslo, Norway. 2. Neonatal Research Group, Health Research Institute Hospital La Fe, Valencia, Spain. 3. Leitat Technological Center, Safety and Sustainability Division, Valencia, Spain. 4. Division of Neonatology, University & Polytechnic Hospital La Fe, Valencia, Spain.
Abstract
BACKGROUND: Perinatal hypoxic-ischemic brain damage is a major cause of mortality and morbidity in the neonatal period. Currently, limited ranges of biochemical tests assessing the intensity and duration of hypoxia are ready for clinical use. However, the need to initiate hypothermia therapy early after the clinical suspicion of hypoxic-ischemic encephalopathy requires the availability of early and reliable hypoxia markers. We have sought these biomarkers in an experimental model of hypoxia reoxygenation. METHODS: Hypoxia and hypotension were induced in newborn piglets following a standardized model and reoxygenation was carried out using room air (RA). An untargeted liquid chromatography-time of flight mass spectrometry (LC-TOFMS) approach was used to assess changes in the metabolomic profile of plasma samples after intense hypoxia and upon reoxygenation. RESULTS: At the end of hypoxia, the plasma metabolome showed an increased plasma concentration of analytes reflecting a metabolic adaptation to prolonged anaerobiosis. However, after resuscitation, metabolite levels returned to the starting values. CONCLUSION: Severe hypoxia induces early, significant, and transient changes of specific metabolites in the plasma metabolome, which represent a snapshot of the biochemical adaptation of mammals to intense hypoxia. These metabolites could have applicability in predicting the severity of hypoxia in the clinical setting.
BACKGROUND: Perinatal hypoxic-ischemic brain damage is a major cause of mortality and morbidity in the neonatal period. Currently, limited ranges of biochemical tests assessing the intensity and duration of hypoxia are ready for clinical use. However, the need to initiate hypothermia therapy early after the clinical suspicion of hypoxic-ischemicencephalopathy requires the availability of early and reliable hypoxia markers. We have sought these biomarkers in an experimental model of hypoxia reoxygenation. METHODS:Hypoxia and hypotension were induced in newborn piglets following a standardized model and reoxygenation was carried out using room air (RA). An untargeted liquid chromatography-time of flight mass spectrometry (LC-TOFMS) approach was used to assess changes in the metabolomic profile of plasma samples after intense hypoxia and upon reoxygenation. RESULTS: At the end of hypoxia, the plasma metabolome showed an increased plasma concentration of analytes reflecting a metabolic adaptation to prolonged anaerobiosis. However, after resuscitation, metabolite levels returned to the starting values. CONCLUSION: Severe hypoxia induces early, significant, and transient changes of specific metabolites in the plasma metabolome, which represent a snapshot of the biochemical adaptation of mammals to intense hypoxia. These metabolites could have applicability in predicting the severity of hypoxia in the clinical setting.
Authors: Aravind Subramanian; Pablo Tamayo; Vamsi K Mootha; Sayan Mukherjee; Benjamin L Ebert; Michael A Gillette; Amanda Paulovich; Scott L Pomeroy; Todd R Golub; Eric S Lander; Jill P Mesirov Journal: Proc Natl Acad Sci U S A Date: 2005-09-30 Impact factor: 11.205
Authors: Jannicke H Andresen; Birgitte Carlsen; Rønnaug Solberg; Lars Mørkrid; Ingeborg L Goverud; Else M Løberg; Ola D Saugstad Journal: J Matern Fetal Neonatal Med Date: 2009-02
Authors: K Sarafidis; N Efstathiou; O Begou; V Soubasi; E Agakidou; E Gika; G Theodoridis; V Drossou Journal: Hippokratia Date: 2017 Apr-Jun Impact factor: 0.471