Lipopolysaccharide Levels in Ex Vivo Lung Perfusion are Associated with Lung Function and Suitability for Transplantation

Abstract

Purpose Ex vivo lung perfusion (EVLP) has emerged as an important platform to assess marginal donor lungs prior to transplantation. Derived from the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS) can stimulate strong immune responses. Studies have shown that donor lungs infected with bacteria may have worse outcomes, suggesting bacteria-induced donor lung injury. However, no large-scale studies have looked at the relationship between LPS levels and donor lung performance on EVLP. Methods LPS levels were measured after one and four hours of perfusion in n=100 clinical EVLP cases. To assess the effects of LPS on lung inflammation, IL-6, 8, 10, and 1β, sTNF-R1, sTREM-1 and ET-1 levels were measured with an ELISA-based platform. Biochemical and physiological assessments were compared to LPS levels. Finally, LPS levels and recipient intensive care unit length of stay after transplantation were investigated. Results There was a significant increase from 0.14 [0.09-0.21] to 0.23 [0.13-0.38] EU/mL (p Conclusion This study demonstrates the trends and importance of circulating LPS levels during EVLP assessment of human donor lung injury. We show that high LPS levels and increasing levels over time were associated with poor donor lung performance in EVLP. These results support the need for therapeutic strategies to target LPS during EVLP, which may improve lung function and rescue more donor lungs for transplantation.