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Predictive biomarkers and metabolic hallmark of postoperative hypoxaemia

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Abstract

Introduction

Pulmonary dysfunctions resulting in postoperative hypoxaemia is a common complication of cardiac surgery. The disease is challenging as it lacks predictive biomarkers. Since a comprehensive metabolic overview of lung microvasculature injury is lacking, we have compared the metabolome of patients undergoing cardiac surgery from blood collected on the first postoperative day from the pulmonary artery and left atrium.

Objectives

To identify predictive biomarkers and metabolic hallmark of pulmonary hypoxaemia.

Methods

Blood samples collected on the first postoperative morning from 47 patients were analysed by nuclear magnetic resonance and multivariate statistics. Patients’ metabolomes were correlated to the level of partial pressure of arterial oxygen (PaO2) without supplementary oxygen treatment measured on the third postoperative day.

Results

Three days postoperatively, 32 patients suffered from hypoxaemia. Spectra recorded on samples collected on the first morning postoperatively revealed metabolic perturbations causing disease progressing. Regression modelling found a 0.97 association between metabolome and PaO2. Classification modelling distinguished patients according to later hypoxaemia. Sixty-four metabolites were identified as the early hallmarks of disease, of which several showed significant correlations with PaO2 (r > 0.55, p ≤ 0.00001). The tricarboxylic acid cycle, amino acid and lipid metabolism, together with redox homeostasis were all found affected. An integrated overview reveals complex cross-talk between pathways that can be related to the pathogenesis of hypoxaemia: damaged alveolar-capillary barrier, edema formation, peroxidation, oxidative stress, impaired antioxidant defense, and cell damage.

Conclusion

Our results indicate unique phenotypes triggering progression into pulmonary dysfunction resulting in postoperative hypoxaemia. The metabolic hallmarks identified offer important targets for future treatments.

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Acknowledgement

The study was financed by Aalborg University Hospital and Aalborg University. The NMR laboratory at Aalborg University is supported by the Obel, SparNord and Carlsberg Foundations.

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Correspondence to Reinhard Wimmer.

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Conflict of interest

R.G.M, B.S.R., M.A.H., S.R.K., S.P. and R.W. have filed a patent application for some of the metabolic biomarkers described in the manuscript and for an algorithm predicting the condition from experimental data.

Ethical approval

The study was approved by the regional ethical committee (N-20080016).

Informed consent

After oral as well as written informed consent was obtained, patients scheduled for elective coronary artery bypass grafting (CABG) were included.

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Maltesen, R.G., Hanifa, M.A., Kucheryavskiy, S. et al. Predictive biomarkers and metabolic hallmark of postoperative hypoxaemia. Metabolomics 12, 87 (2016). https://doi.org/10.1007/s11306-016-1018-5

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