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

## TL;DR

This study shows that portal venous drainage in intestinal transplants leads to better immune and cell survival responses in pigs compared to systemic drainage.

## Contribution

The study identifies portal venous drainage as a key factor in modulating early immunometabolic responses after intestinal transplantation.

## Key findings

- Portal drainage was associated with a more regulated immunometabolic profile and early apoptotic modulation.
- IL-1α expression was selectively upregulated in the portal group, indicating early mucosal immune activation.
- PCA confirmed a distinct immunometabolic profile under portal drainage, suggesting improved mucosal adaptation.

## Abstract

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.

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.

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.

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.

Portal venous drainage in a swine model of living‐donor intestinal transplantation promoted a more balanced immunometabolic profile, with early apoptotic modulation and increased IL‐1α expression, suggesting improved mucosal adaptation compared with systemic drainage.