Portal Venous Drainage Modulates Inflammatory and Apoptotic Responses in a Swine Model of Living Donor Intestinal Transplantation

BACKGROUND: Intestinal failure in children, when unresponsive to rehabilitation, requires intestinal transplantation as the only definitive therapy. In regions with limited availability of deceased donors, living-donor intestinal transplantation (LDIT) represents an important alternative. The early immunometabolic consequences of venous drainage configuration, however, remain insufficiently defined. Because ischemia-reperfusion injury is central to graft dysfunction, understanding how portal versus systemic venous outflow shapes the immediate postoperative response is essential to guide pediatric strategies. METHODS: A juvenile swine model (n = 14) was used to compare portal (n = 7) and systemic (caval, n = 7) venous drainage after LDIT. Animals were followed for 4 days with serial biochemical, histological, immunohistochemical, and molecular assessments. Analyses included linear mixed-effects models (LMM) for repeated measures and principal component analysis (PCA) to integrate multivariable data and identify global immunometabolic patterns. RESULTS: Hepatic and renal function were preserved in both groups. Histology revealed only mild ischemia-reperfusion injury (Chiu/Park grades 1-2), with a trend toward greater lymphocytic infiltration in the systemic group. Caspase immunohistochemistry demonstrated early apoptotic activation in the portal group, which declined by day 4, suggesting a controlled adaptive response. IL-1α expression was selectively upregulated in intestinal tissue from the portal group, consistent with early mucosal immune activation. PCA confirmed a distinct immunometabolic profile under portal drainage, characterized by balanced inflammation, controlled apoptosis, and trends toward enhanced protein synthesis. CONCLUSION: Venous drainage configuration modulates early biological responses after LDIT. Portal drainage was associated with a more regulated immunometabolic profile, supporting the hypothesis that physiological venous outflow promotes mucosal protection and immune balance.