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Portal Venous Drainage Modulates Inflammatory and Apoptotic Responses in a Swine Model of Living Donor Intestinal
Guilherme F Paganoti1, Uenis Tannuri1, Alessandro R Belon2
1Institute for Children and Adolescents at the University of São Paulo, São Paulo, Brazil.
Insights
Living-donor intestinal transplantation (LDIT) with portal venous drainage shows a more regulated immunometabolic profile, promoting mucosal protection and immune balance. This approach is crucial for pediatric strategies when deceased donors are unavailable.
Area of Science:
- Pediatric surgery
- Transplantation immunology
- Gastroenterology
Background:
- Intestinal transplantation is vital for children with intestinal failure unresponsive to rehabilitation.
- Living-donor intestinal transplantation (LDIT) is an alternative where deceased donors are scarce.
- Early immunometabolic effects of venous drainage in LDIT require further definition.
Purpose of the Study:
- To compare the early immunometabolic consequences of portal versus systemic venous drainage after LDIT.
- To understand how venous outflow configuration impacts immediate postoperative responses in pediatric LDIT.
Main Methods:
- A juvenile swine model (n=14) was used to compare portal (n=7) and systemic (n=7) venous drainage after LDIT.
- Serial biochemical, histological, immunohistochemical, and molecular assessments were performed over 4 days.
- Linear mixed-effects models and principal component analysis (PCA) integrated multivariable data.
Main Results:
- Both drainage groups maintained hepatic and renal function with mild ischemia-reperfusion injury.
- Portal drainage showed controlled apoptosis and selective IL-1α upregulation in intestinal tissue, indicating immune activation.
- PCA revealed a distinct immunometabolic profile under portal drainage, with balanced inflammation and enhanced protein synthesis trends.
Conclusions:
- Venous drainage configuration significantly influences early biological responses post-LDIT.
- Portal drainage is associated with a more regulated immunometabolic profile, suggesting enhanced mucosal protection and immune balance.
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.
