Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model

Abstract

Background. Normothermic ex vivo lung perfusion (EVLP) increases the pool of donor lungs by requalifying marginal lungs refused for transplantation through the recovery of macroscopic and functional properties. However, the cell response and metabolism occurring during EVLP generate a nonphysiological accumulation of electrolytes, metabolites, cytokines, and other cellular byproducts which may have deleterious effects both at the organ and cell levels, with impact on transplantation outcomes. Methods. We analyzed the physiological, metabolic, and genome-wide response of lungs undergoing a 6-h EVLP procedure in a pig model in 4 experimental conditions: without perfusate modification, with partial replacement of fluid, and with adult or pediatric dialysis filters. Results. Adult and pediatric dialysis stabilized the electrolytic and metabolic profiles while maintaining acid-base and gas exchanges. Pediatric dialysis increased the level of IL-10 and IL-6 in the perfusate. Despite leading to modification of the perfusate composition, the 4 EVLP conditions did not affect the gene expression profiles, which were associated in all cases with increased cell survival, cell proliferation, inflammatory response and cell movement, and with inhibition of bleeding. Conclusions. Management of EVLP perfusate by periodic replacement and continuous dialysis has no significant effect on the lung function nor on the gene expression profiles ex vivo. These results suggest that the accumulation of dialyzable cell products does not significantly alter the lung cell response during EVLP, a finding that may have impact on EVLP management in the clinic.

Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation

“…De Wolf et al investigated whether dialysis during EVLP affects lung function and pro-inflammatory gene expression but were unable to show a clear benefit of dialysis. 40 Iskender et al reported that cytokine filtration during EVLP could reduce inflammatory cytokines FIGURE 7. Electron microscopic assessment of lower lobes.…”

“…De Wolf et al investigated whether dialysis during EVLP affects lung function and pro-inflammatory gene expression but were unable to show a clear benefit of dialysis. 40 Iskender et al reported that cytokine filtration during EVLP could reduce inflammatory cytokines and development of pulmonary edema. 41 Our data showed elevations in inflammatory cytokines in EVLP2, which may be partially associated with impaired organ function.…”

Diagnostic and Therapeutic Implications of Ex Vivo Lung Perfusion in Lung Transplantation: Potential Benefits and Inherent Limitations

“…Based on the Toronto protocol, Takahashi et al modified the perfusion method using a syringe infusion pump for continuous delivery of Steen and a multichannel syringe pump for continuous collection of the perfusate, resulting in a significant reduction in IL-6 and IL-8 levels in EVLP perfusate. 115 Nevertheless, because of a greater demand for Steen, this modified perfusion method is of operational complexity and high cost. Wei et al demonstrated the safety and feasibility of installing a dialyzer in the EVLP circuit of porcine lungs instead of frequently exchanging the perfusate.…”

A cross-circulatory platform for monitoring innate responses in lung grafts

“…The lung harvest from donor pigs (n = 10) was performed in the Animal Surgery and Medical Imaging Platform (CIMA-MIMA2-BREED-INRAE, Jouy en Josas, France). Heart-lung monobloc harvests were performed using a non-heart-beating donor swine model 33 . Anesthesia was induced by a combination of 1 mg/kg Rompun® 2% (Elanco, Heinz-Lohmann-Strasse 4, Cuxhaven,Germany) and 15 mg/kg Imalgene® 1000 (Boehringer Ingelheim Animal Health, Lyon, France) and pursued with 6% iso uorane.…”