Triptolide Attenuates Graft Inflammation During Ex Vivo Lung Perfusion

Purpose Ex vivo lung perfusion (EVLP) has been proposed as a platform for lung graft assessment and preservation. However, its proinflammatory milieu may be associated with deterioration in graft quality which may contribute to posttransplant graft dysfunction. Triptolide (TL), a diterpenoid triepoxide, has recently been shown to have a therapeutic potential in various disease states due to its anti-inflammatory properties. Based on this, we sought to assess the impact of TL on graft preservation during EVLP as well as associated posttransplant outcomes. Methods Using rat heart-lung blocs, EVLP was performed with Steen solution containing 100 nM of TL at 37°C for 4 hours. Graft evaluation included physiologic, metabolic and functional parameters. Tissue inflammatory profile and endoplasmic reticulum (ER) stress markers were assessed. Following 4 hours of EVLP, orthotopic single lung transplantation was performed using 3-cuff technique. Results were compared with those of lung grafts undergoing EVLP without TL. Results Physiologic and functional parameters of lung grafts on EVLP with TL were better than those without treatment (Figure A). Glucose consumption was significantly decreased in lungs treated with TL. Levels of proinflammatory cytokine mRNA were lower in TL-treated lungs which is attributed to inhibition of nuclear factor κB (NF-κB) signaling. In addition, TL improved ER stress during EVLP as evidenced by diminished ER stress markers. Most importantly, posttransplant graft function was significantly better in the TL group compared to untreated group (Figure C). Conclusion Treatment of lung grafts with TL during EVLP may serve as a potential compound for enhanced graft preservation. These studies warrant further investigation into its potential protective effect and may have implications for improving posttransplant outcomes.