Modeling the kinetics of interorgan arginine metabolism during bacterial sepsis in swine

Authors: VONDEROHE, CAITLIN - Baylor College Of Medicine; Burrin, Douglas

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2025
Publication Date: 1/29/2025
Citation: Vonderohe, C., Burrin, D.G. 2025. Modeling the kinetics of interorgan arginine metabolism during bacterial sepsis in swine. American Journal of Physiology. 328:G309-G310. https://doi.org/10.1152/ajpgi.00375.2024.
DOI: https://doi.org/10.1152/ajpgi.00375.2024

Interpretive Summary: This study highlights the complexity of preclinical studies to assess the metabolic impact of sepsis. There has been debate in the 'eld as to what is the best approach to simulate sepsis in animal models, some using endotoxin, cecalligation and puncture, where others infuse various species of live bacteria. An important goal in re'ning future preclinical models of sepsis also should be increasing the standardization and reporting of details of the experimental design,approach, and outcomes used. This study demonstrates how the use of transorgan amino acid kinetics using stable isotopes can be combined with clinically-relevant bacterial sepsis in swine to assess the longitudinal changes in metabolism. These features highlight the advantages of using swine and hopefully will spur other groups to examine more detailed changes in tissue and organ speci'c immune responses to infection as well as how therapeutic interventions can stem the pro-in'ammatory response and tissue injury.

Technical Abstract: Researchers utilize a multicatheterized swine model with stable isotope tracers to investigate whole-body arginine metabolism during early sepsis induced by Pseudomonas aeruginosa. Arginine, a conditionally essential amino acid during critical illness, is central to nitric oxide (NO) synthesis and immune regulation. In sepsis, despite increased protein catabolism and a large net release of amino acids—including a sixfold increase in hindquarter arginine efflux—arterial arginine concentrations remained unchanged. This suggests a temporal delay in the onset of arginine deficiency seen in later stages of sepsis. Elevated hepatic and splanchnic uptake of arginine coincided with increased whole-body urea and ornithine production, implicating enhanced arginase activity over NO synthase, as no significant rise in systemic NO production was observed. These findings highlight a metabolic shift favoring arginine catabolism via arginase rather than NO pathways during early sepsis. The swine model’s physiological similarity to humans enabled transorgan balance measurements not feasible in clinical settings. Additionally, analysis of arterial-venous concentration gradients was refined using ANCOVA, improving sensitivity and interpretability of metabolic flux data. Overall, this study provides insight into the dynamic redistribution and catabolism of arginine in sepsis, with implications for therapeutic strategies aimed at modulating arginine availability and downstream immune-metabolic responses.