Abstract 4365882: Divergent Transcriptomic Responses in Liver and Colon after ECMO resuscitation in an Infant Piglet Model

Introduction and Background: Pediatric patients on ECMO therapy often experience multiorgan dysfunction, including liver injury and intestinal mucosal disruption. RNA sequencing (RNA-seq) can identify transcriptomic changes at the cellular level. Goals: This study used a piglet model to examine transcriptomic alterations in the liver and colon following ECMO resuscitation, aiming to characterize ECMO’s impact on the gut-liver axis. Methods: Four specific piglets underwent KCl-induced cardiac arrest (5-, 10-, 15-, or 20-minute circulatory arrest), followed by 4 hours of ECMO via external jugular vein and carotid artery cannulation, and were compared to 9 mechanical ventilation controls. After euthanasia, liver and colon samples were processed for RNA-seq. Porcine RNA-seq data were converted to orthologous human genes for gene cluster enrichment. Results: All ECMO piglets completed the protocol. Postmortem examination of ECMO-treated animals revealed discoloration of the colon and dense adhesions, though its anatomical structure was preserved. RNA-seq identified 560 downregulated and 144 upregulated genes in the colon, and 1118 downregulated and 1373 upregulated genes in the liver. Both organs showed upregulation of genes related to mitochondrial function and oxidative phosphorylation. The colon exhibited upregulation of immune-related genes, particularly those involved in antiviral defense and interferon response (Figure 1A). In contrast, the liver showed downregulation of immune-related and defense genes (Figure 2A). While proliferation pathways were upregulated in both organs, the colon shifted toward a less differentiated state with increased expression of HOX genes linked to Wnt signaling and dedifferentiated cell proliferation (Figure 1B). Liver expression showed upregulation of genes related to DNA replication and mitotic activity, as well as translational machinery (Figure 2B). Conclusions: ECMO induces significant and diverse transcriptomic changes in the colon and liver in this piglet model. Both organs showed increased gene expression related to proliferation, though the colon exhibited a more dedifferentiated profile, suggesting the urgent need for mucosal barrier restoration. The upregulation of immunologic genes in the colon, contrasted with immune suppression in the liver, highlights the potential for therapies that target gut epithelial integrity and immune modulation to reduce gastrointestinal and hepatic complications in ECMO patients.