Challenging the ex vivo lung perfusion procedure with continuous dialysis in a pig model
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Bibliographic record
Abstract
Ex Vivo Lung Perfusion (EVLP) is an innovative technique that enhances the function of donor lungs with extended criteria, thus increasing the number of organs available for transplantation. By ventilating and perfusing the lungs at normothermia, this method allows for the recovery of lungs of uncertain quality and makes them suitable for transplantation. However, prolonged EVLP can lead to edema, inflammatory responses, and the accumulation of metabolic waste. To address these limitations, my thesis work explored the effect of integrating a hemodialyzer into the EVLP circuit to regulate the composition of the perfusion fluid and maintain lung viability, evaluating the biological effects over 6 and 12 hours in a porcine model.MethodsThe experiments were conducted in accordance with EU guidelines and French regulations, approved by the COMETHEA ethics committee. Sixteen pigs were divided into four EVLP groups: without perfusion fluid change, hourly partial replacement (TORONTO protocol), pediatric dialysis, and adult dialysis. Pediatric dialysis used a membrane with an effective surface area of 0.2 m² and a filtration threshold of 30 kDa, while adult dialysis used a membrane with an effective surface area of 1.8 m² and a filtration threshold of 40 kDa. The first study was conducted over 6 hours with all four groups, and the second over 12 hours with the hourly partial replacement and pediatric dialysis groups.Physiological and metabolic parameters were measured, cytokines were assayed by Luminex/Multiplex, and gene expression profiles were evaluated by RNA sequencing.ResultsAnalysis of physiological parameters showed stability in lung compliance, pulmonary arterial pressure, and gas exchange without significant differences between groups. The dialysis procedures corrected electrolyte and metabolic imbalances, stabilizing lactate and glucose concentrations. However, inflammatory cytokines (TNFα, IL-6, IL-8, IL-10) increased after three hours, with higher levels in the pediatric dialysis group.Gene expression analyses revealed that EVLP is associated, regardless of group, with the activation of inflammatory pathways, cell survival, and proliferation. In contrast, pediatric dialysis induced expression profiles predictive of stronger endothelial activation and cytokine signaling compared to hourly partial replacement.ConclusionThe addition of a dialysis circuit to the EVLP protocol allows for better electrolyte and metabolic balance in the perfusion fluid. However, this approach is associated with an increase in inflammatory cytokines, which could have negative implications for lung transplantation. Despite promising prospects, further evaluations and improvements are necessary before clinical application, including the use of enhanced adsorption membranes and the addition of nutrients to optimize the perfusion system. These results highlight the importance of functional genomic analyses to understand the biological response to EVLP and guide future improvements.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it