Intestinal Barrier Dysfunction and Stem Cell Impairment Following Cardiac Surgery in Pigs: A Porcine Model Study

Cardiac surgery induces systemic stress responses that may compromise intestinal homeostasis in animal patients, yet the underlying mechanisms remain poorly understood. This study investigated postoperative intestinal pathophysiology in a porcine model, focusing on the activation of the NF-κB pathway and its impact on intestinal stem cell function. Thirty-two large white pigs (40–50 kg) were randomized into control and model groups; the model group underwent simulated cardiac procedures involving aortotomy and left ventricular outflow tract exposure under standardized anesthesia. Our findings revealed significant NF-κB pathway activation and upregulation of matrix metalloproteinases (MMPs) in the intestine following surgery. Intestinal stem cells isolated from crypts showed downregulated expression of key barrier proteins. Notably, organoids derived from the model group exhibited impaired early proliferative capacity and delayed morphogenesis, despite preserved differentiation potential upon extended culture. This suggests a stress-induced state that favors the maintenance of stemness over commitment to differentiation. These results delineate an NF-κB/MMP-mediated mechanism linking surgical stress to intestinal barrier dysfunction and stem cell dysregulation in this large animal model. Crucially, the study provides insights that may help improve perioperative care and reduce gastrointestinal complications in animal patients undergoing major surgeries, thereby enhancing animal welfare. The identified pathways offer potential targets for developing supportive therapies in veterinary practice.