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Changes in infant porcine pulmonary tissue oxylipins induced by cardiopulmonary bypass
Kelsey G Iguidbashian1, Justin Robison2, Ludmila Khailova1
1Department of Pediatrics, University of Colorado/Children's Hospital of Colorado, Aurora, CO, USA.
Insights
Cardiopulmonary bypass with deep hypothermic circulatory arrest significantly increases pulmonary tissue arachidonic acid metabolites in infant pigs. These changes involve multiple metabolic pathways, highlighting potential targets for understanding CPB-induced lung injury.
Area of Science:
- Biochemistry
- Physiology
- Pediatric Research
Background:
- Oxylipins, derived from fatty acids like arachidonic acid (AA), are crucial in inflammation and tissue injury.
- While serum oxylipins rise post-cardiopulmonary bypass (CPB) in adults, pulmonary tissue changes remain unclear.
- Infant pigs undergoing CPB with deep hypothermic circulatory arrest (DHCA) provide a model to study these effects.
Purpose of the Study:
- To investigate pulmonary tissue oxylipin profiles in an infant porcine model subjected to CPB with DHCA.
- To characterize the specific metabolic pathways (CYP450, LOX, COX) involved in arachidonic acid metabolism in lung tissue post-CPB/DHCA.
- To identify differences in oxylipin levels between CPB/DHCA-exposed and control groups.
Main Methods:
- Infant pigs were divided into CPB/DHCA and control (anesthesia only) groups.
- Lung tissue (right upper and lower lobes) was collected for oxylipin analysis.
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for quantification.
- One-way ANOVA and pairwise comparisons were employed for statistical analysis.
Main Results:
- Arachidonic acid (AA) and its metabolites from CYP450, LOX, and COX pathways were significantly elevated in both lung lobes of pigs after CPB/DHCA compared to controls.
- Multiple prostaglandin metabolites, generated via the COX pathway, were also significantly increased in the lower lobes of control animals.
- This indicates CPB/DHCA induces widespread pulmonary AA metabolite production, with some regional differences.
Conclusions:
- CPB/DHCA significantly elevates pulmonary tissue AA and its metabolites through COX, LOX, and CYP450 pathways.
- Elevated prostaglandins in control lower lobes suggest a mechanism independent of CPB/DHCA, possibly related to mechanical ventilation.
- Further research on oxylipins is essential for understanding and mitigating CPB-induced acute lung injury in infants.
Background:
Oxylipins are metabolites derived from fatty acids such as arachidonic acid (AA) and are key mediators in inflammation, host defense, and tissue injury. Serum oxylipins increase in adults after cardiopulmonary bypass (CPB) but tissue-level changes are poorly defined. The objective of this study was to characterize pulmonary tissue oxylipins in an infant porcine model of CPB with deep hypothermic circulatory arrest (DHCA).
Methods:
Infant pigs underwent CPB with DHCA. Controls received anesthesia only. Right upper and lower lobes of the lung underwent oxylipin analysis via liquid chromatography-tandem mass spectrometry. One-way ANOVA was utilized to assess differences in oxylipin concentrations across groups, followed by pairwise comparisons.
Results:
AA and multiple AA metabolites via cytochrome P450 (CYP450), lipoxygenase (LOX), and cyclooxygenase (COX) pathways were significantly increased in the upper and lower lobe of pigs exposed to CPB/DHCA as compared to controls. Multiple prostaglandin metabolites produced via COX were also significantly elevated in the lower lobes of control animals.
Conclusions:
CPB/DHCA induces a significant increase in pulmonary tissue AA, with subsequent metabolism via COX, LOX, and CYP450 pathways. Interestingly, prostaglandins were also elevated in the lower lobes of the controls, suggesting a mechanism separate from CPB/DHCA. Future oxylipin studies are needed to better understand CPB-induced acute lung injury.
Impact:
CPB/DHCA and, to a lesser extent, lung region influence pulmonary tissue-level AA metabolite production. Inflammatory mediator AA metabolites have been noted in previous studies to increase following CPB; however, this is the first study to look at pulmonary tissue-level differences following CPB/DHCA. Increases in many AA metabolites, including LOX- and CYP450-derived products, were seen in both upper and lower lobe of piglets following CPB/DHCA. COX-derived prostaglandin metabolites were increased not only in CPB upper and lower lobe but also in mechanically ventilated control lower lobe, suggesting an additional, separate mechanism from CPB/DCHA.
