Prolonged dialysis during ex vivo lung perfusion promotes inflammatory responses
Résumé
Ex-vivo lung perfusion (EVLP) has extended the number of transplantable lungs by reconditioning marginal organs. However, EVLP is performed at 37°C without homeostatic regulation leading to metabolic wastes' accumulation in the perfusate and, as a corrective measure, the costly perfusate is repeatedly replaced during the standard of care procedure. As an interesting alternative, a hemodialyzer could be placed on the EVLP circuit, which was previously shown to rebalance the perfusate composition and to maintain lung function and viability without appearing to impact the global gene expression in the lung. Here, we assessed the biological effects of a hemodialyzer during EVLP by performing biochemical and refined functional genomic analyses over a 12h procedure in a pig model. We found that dialysis stabilized electrolytic and metabolic parameters of the perfusate but enhanced the gene expression and protein accumulation of several inflammatory cytokines and promoted a genomic profile predicting higher endothelial activation already at 6h and higher immune cytokine signaling at 12h. Therefore, epuration of EVLP with a dialyzer, while correcting features of the perfusate composition and maintaining the respiratory function, promotes inflammatory responses in the tissue. This finding suggests that modifying the metabolite composition of the perfusate by dialysis during EVLP can have detrimental effects on the tissue response and that this strategy should not be transferred as such to the clinic.
Mots clés
lung
transplantation
ex vivo
ischemia-reperfusion
dialysis
ex vivo lung perfusion
pig EVLP
ex-vivo lung perfusion GS
Gold Standard PD
Pediatric Dialysis LDH
lactate deshydrogenase
DEGs
differentially expressed genes FCs
fold changes IPA
ingenuity pathways analysis
ex-vivo lung perfusion
GS
Gold Standard
PD
Pediatric Dialysis
LDH
differentially expressed genes
FCs
fold changes
IPA
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY - Paternité
Licence : CC BY - Paternité
