Ex vivo lung perfusion moderates gene expression differences between cardiac death and brain death donor lungs

Abstract

Donation after cardiac death (DCD) donor lungs have been shown to express less proinflammatory genes than donation after brain death (DBD) lungs, likely due to the absence of brain-death related inflammatory physiology. However, it is unclear whether this difference is clinically significant following reperfusion. To avoid confounding by the recipient immune system and activation state, we utilized ex vivo lung perfusion (EVLP) as a reperfusion-like event and examined the effect of EVLP on the transcriptome of DCD (n = 39) and DBD (n = 49) lungs. To validate our RNA results, banked EVLP perfusates from a separate cohort of DCD (n = 24) and DBD (n = 24) cases were assayed for IL-6, IL-8, IL-10, IL-1β, soluble TNFα receptor-1 (sTNFR1), and soluble triggering receptor expressed on myeloid cells-1 (sTREM1) protein levels at 15 minutes intervals for 3 hours. While DCD lungs demonstrated lower levels of proinflammatory transcripts and perfusate cytokine protein levels than DBD lungs prior to EVLP, after EVLP, there were no significant gene expression differences or cytokine protein levels between groups. Therefore, while DCD and DBD lungs differ by the amounts of proinflammatory cytokines following procurement, the propagation of inflammation becomes limited during EVLP, and DBD and DCD lungs reach a similar plateau of transcript expression, including proinflammatory cytokines at the end of perfusion. EVLP may therefore play a preconditioning role by dampening the proinflammatory state prior to transplant reperfusion.

Keywords

• lung transplantation
• brain-death
• donation after cardiac death
• ex vivo lung perfusion
• cytokines