Activation of kynurenine pathway of tryptophan metabolism after infant cardiac surgery with cardiopulmonary bypass: a pr
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SHORT COMMUNICATION
Activation of kynurenine pathway of tryptophan metabolism after infant cardiac surgery with cardiopulmonary bypass: a prospective cohort study Divya Sabapathy1 · Jelena Klawitter2 · Lori Silveira3 · Ludmila Khailova4 · Max B. Mitchell5 · Gareth J. Morgan4 · Michael V. DiMaria4 · Mark Twite2 · Benjamin S. Frank4 · Jesse A. Davidson4 Received: 19 May 2020 / Accepted: 18 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background Serum kynurenic acid is associated with poor outcomes after infant cardiopulmonary bypass (CPB), but comprehensive mapping of the kynurenine pathway (KP) after CPB has yet to be performed. Aims To map changes in the KP induced by infant CPB. Methods Compared changes in serum KP metabolites through 48hrs post-op with liquid-chromatography-tandem mass spectrometry. Results Infant CPB results in marked increase in proximal, but not distal metabolites of the KP. Conclusions Infant CPB leads to accumulation of circulating KP metabolites, which have important neurologic and immunologic activities. Thus, further exploration of the KP is warranted in these high-risk infants. Keywords Targeted metabolomics · Kynurenic acid · Quinolinic acid · Congenital heart disease · Single ventricle palliation · Bidirectional glenn
1 Introduction
Benjamin S. Frank and Jesse A. Davidson contributed equally as senior authors of this manuscript. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11306-020-01714-x) contains supplementary material, which is available to authorized users. * Jesse A. Davidson [email protected] 1
University of Colorado Denver Department of Pediatrics, 13123 East 16th Ave, Box 100, Aurora, CO 80045, USA
2
University of Colorado Denver Department of Anesthesiology, 13123 East 16th Ave, Box 100, Aurora, CO 80045, USA
3
University of Colorado Denver Department of Biostatistics, 13123 East 16th Ave, Box 100, Aurora, CO 80045, USA
4
Section of Cardiology, University of Colorado Denver Department of Pediatrics, 13123 East 16th Ave, Box 100, Aurora, CO 80045, USA
5
University of Colorado Denver Department of Surgery, 13123 East 16th Ave, Box 100, Aurora, CO 80045, USA
Congenital heart disease (CHD) is the most common birth defect in the United States, with an incidence of 4–14 per 1000 live births (Hoffman and Kaplan 2002). Single ventricle heart disease (SVHD) is one of the most severe types of CHD, in which there is one functional pumping chamber, rendering it uniformly fatal without intervention. While there is no cure, SVHD patients have the potential to survive into adulthood with surgical palliation in early childhood. Like other forms of severe CHD, this cohort of patients is particularly vulnerable given their chronic heart failure, cyanosis, and need for multiple surgeries with cardiopulmonary bypass (CPB). Children undergoing cardiothoracic surgery with CPB endure significant physiologic stress as a result of surgical trauma, a
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