Development of Transplant Surgeon-Innovated Ex Vivo Machine Perfusion: Validation in a Porcine Donation after Circulatory Death-Simulated Liver Transplant Model

Abstract

Purpose: Ex vivo machine perfusion (EVMP) is increasingly recognized as a promising technique for enhancing the preservation and viability of donor organs, particularly in donation after circulatory death (DCD) liver transplantation (LT). This study validates a transplant surgeon-innovated EVMP protocol by assessing its efficacy in preserving liver function and reducing ischemia-reperfusion injury (IRI) in a porcine DCD-simulated liver transplant (DCD sLT) model. Materials and Methods: Twenty Yorkshire pigs were used to compare static cold storage (SCS) and EVMP. In Model 1, the SCS group (n=5) underwent 5 hours of cold storage, while the EVMP group (n=9) had 1 hour of cold storage followed by 4 hours of EVMP. In Model 2, the SCS group (n=3) underwent 6 hours of cold storage, while the EVMP group (n=3) had 2 hours of cold storage followed by 4 hours of EVMP. Hemodynamic stability during perfusion, laboratory findings, and apoptosis (via TUNEL assay) after reperfusion were evaluated. Results: The EVMP system was successfully used all 12 cases without technical complications. Hemodynamic parameters remained stable throughout perfusion. In Model 2, alanine aminotransferase levels were significantly lower in the EVMP group compared to the SCS group (e.g., 134.3 +/- 27.0 U/L vs. 48.0 +/- 6.2 U/L, p=0.006 at 3 hours post-reperfusion). TUNEL staining revealed significantly reduced hepatic apoptosis in the EVMP group compared to the SCS group at 2 and 3 hours post-reperfusion in both models. Conclusion: This study successfully demonstrated the stability of the transplant surgeon-innovated normothermic EVMP protocol, validating its efficacy in improving organ preservation and reducing IRI in a porcine DCD sLT model.