Metabolomic Analyses of Plasma Reveals New Insights into Asphyxia and Resuscitation in Pigs

PLoS One

Therese Koal¹  Hans-Peter Deigner¹  Sabine Scholl-Bürgi¹  David Enot²  Matthias Keller³  Rønnaug Solberg³  Ola D. Saugstad⁴ 

[1] BIOCRATES Life Sciences AG, Innsbruck, Austria;Department for Surgical Research, Oslo University Hospital, Rikshospitalet, University of Oslo, Norway;Department of Pediatric Research, Oslo University Hospital, Rikshospitalet, University of Oslo, Norway;Innsbruck Medical University, Department of Pediatrics IV, Division of Neuropediatrics and Inherited Metabolic Disorders, Innsbruck, Austria

关键词: Hypoxia;    Metabolites;    Resuscitation;    Asphyxia;    Oxygen;    Oxygen metabolism;    Biomarkers;    Swine;   

DOI  :  10.1371/journal.pone.0009606

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background Currently, a limited range of biochemical tests for hypoxia are in clinical use. Early diagnostic and functional biomarkers that mirror cellular metabolism and recovery during resuscitation are lacking. We hypothesized that the quantification of metabolites after hypoxia and resuscitation would enable the detection of markers of hypoxia as well as markers enabling the monitoring and evaluation of resuscitation strategies.Methods and Findings Hypoxemia of different durations was induced in newborn piglets before randomization for resuscitation with 21% or 100% oxygen for 15 min or prolonged hyperoxia. Metabolites were measured in plasma taken before and after hypoxia as well as after resuscitation. Lactate, pH and base deficit did not correlate with the duration of hypoxia. In contrast to these, we detected the ratios of alanine to branched chained amino acids (Ala/BCAA; R2.adj = 0.58, q-value<0.001) and of glycine to BCAA (Gly/BCAA; R2.adj = 0.45, q-value<0.005), which were highly correlated with the duration of hypoxia. Combinations of metabolites and ratios increased the correlation to R2adjust = 0.92. Reoxygenation with 100% oxygen delayed cellular metabolic recovery. Reoxygenation with different concentrations of oxygen reduced lactate levels to a similar extent. In contrast, metabolites of the Krebs cycle (which is directly linked to mitochondrial function) including alpha keto-glutarate, succinate and fumarate were significantly reduced at different rates depending on the resuscitation, showing a delay in recovery in the 100% reoxygenation groups. Additional metabolites showing different responses to reoxygenation include oxysterols and acylcarnitines (n = 8–11, q<0.001).Conclusions This study provides a novel strategy and set of biomarkers. It provides biochemical in vivo data that resuscitation with 100% oxygen delays cellular recovery. In addition, the oxysterol increase raises concerns about the safety of 100% O2 resuscitation. Our biomarkers can be used in a broad clinical setting for evaluation or the prediction of damage in conditions associated with low tissue oxygenation in both infancy and adulthood. These findings have to be validated in human trials.

【 授权许可】

CC BY