Iguidbashian 2022 Changes in infant porcine pulmonary tissue oxylipins.pdf

<p>BACKGROUND: Oxylipins are metabolites derived from fatty acids such as arachidonic acid (AA) and are key mediators in</p> <p>inflammation, host defense, and tissue injury. Serum oxylipins increase in adults after cardiopulmonary bypass (CPB) but tissue-level</p> <p>changes are poorly defined. The objective of this study was to characterize pulmonary tissue oxylipins in an infant porcine model of</p> <p>CPB with deep hypothermic circulatory arrest (DHCA).</p> <p>METHODS: Infant pigs underwent CPB with DHCA. Controls received anesthesia only. Right upper and lower lobes of the lung</p> <p>underwent oxylipin analysis via liquid chromatography–tandem mass spectrometry. One-way ANOVA was utilized to assess</p> <p>differences in oxylipin concentrations across groups, followed by pairwise comparisons.</p> <p>RESULTS: AA and multiple AA metabolites via cytochrome P450 (CYP450), lipoxygenase (LOX), and cyclooxygenase (COX)</p> <p>pathways were significantly increased in the upper and lower lobe of pigs exposed to CPB/DHCA as compared to controls. Multiple</p> <p>prostaglandin metabolites produced via COX were also significantly elevated in the lower lobes of control animals.</p> <p>CONCLUSIONS: CPB/DHCA induces a significant increase in pulmonary tissue AA, with subsequent metabolism via COX, LOX, and</p> <p>CYP450 pathways. Interestingly, prostaglandins were also elevated in the lower lobes of the controls, suggesting a mechanism</p> <p>separate from CPB/DHCA. Future oxylipin studies are needed to better understand CPB-induced acute lung injury.</p> <p>Pediatric Research (2022) 92:1274–1281; https://doi.org/10.1038/s41390-022-02125-5</p> <p>IMPACT:</p> <p>● CPB/DHCA and, to a lesser extent, lung region influence pulmonary tissue-level AA metabolite production.</p> <p>● Inflammatory mediator AA metabolites have been noted in previous studies to increase following CPB; however, this is the first</p> <p>study to look at pulmonary tissue-level differences following CPB/DHCA.</p> <p>● Increases in many AA metabolites, including LOX- and CYP450-derived products, were seen in both upper and lower lobe of</p> <p>piglets following CPB/DHCA.</p> <p>● COX-derived prostaglandin metabolites were increased not only in CPB upper and lower lobe but also in mechanically</p> <p>ventilated control lower lobe, suggesting an additional, separate mechanism from CPB/DCHA.</p>