Background: Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection.Methods: We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n = 59) who underwent lung transplantation off‐pump (n = 26), with cardiopulmonary bypass (CPB; n = 18), or with extracorporeal membrane oxygenation (ECMO; n = 15). Peripheral blood was collected from patients at baseline and at 6 and 72 h after reperfusion. To adjust for clinical differences between groups, we utilized a linear mixed model with overlap weighting.Results: PGD3 was present at 48 or 72 h after reperfusion in 7.7% (2/26) of off‐pump cases, 20.0% (3/15) of ECMO cases, and 38.9% (7/18) of CPB cases (p = 0.04). The ECMO and CPB groups had greater reperfusion‐induced increases in MIP‐1B, IL‐6, IL‐8, IL‐9, IL1‐ra, TNF‐alpha, RANTES, eotaxin, IP‐10, and MCP‐1 levels than the off‐pump group. Cytokine expression profiles after reperfusion were not significantly different between ECMO and CPB groups.Conclusion: Our data suggest that, compared with an off‐pump approach, the intraoperative use of ECMO or CPB during lung transplantation is associated with greater reperfusion‐induced cytokine release and graft injury.

Primary graft dysfunction (PGD) is a major cause of early morbidity and mortality after lung transplantation. During blood-based ex vivo lung perfusion (EVLP), hemolysis releases plasma-free hemoglobin (pfHb) and other erythrocyte-derived products that may promote endothelial injury and inflammation. We investigated whether EVLP-associated hemolysis is associated with cytokine release, endothelial dysfunction, and grade 3 PGD (PGD3). In this prospective, single-center observational study, end-EVLP perfusate from 57 double-lung transplant recipients supported with the Organ Care System Lung was analyzed for pfHb, 26 cytokines, blood counts, and associations with PGD3 within 72 h after transplantation. A mock EVLP blood-loop model was used to evaluate the effects of red blood cell storage duration and circuit run time on hemolysis. Generated hemolytic perfusates were applied to human lung microvascular endothelial cells to assess barrier injury and inflammatory activation. Among the 57 recipients, 32 (56.1%) developed PGD3 at any time point within 72 h after transplantation. Higher end-EVLP pfHb, interleukin-6, and interleukin-8 levels were associated with PGD3, and pfHb correlated positively with interleukin-6 and interleukin-8. Hemolysis increased with longer blood storage and EVLP duration, with storage duration emerging as the dominant contributor in the blood-loop model. Hemolytic perfusate disrupted endothelial junctions, increased permeability, and induced interleukin-6 and interleukin-8 release. EVLP-associated hemolysis is linked to endothelial barrier injury, inflammatory activation, and PGD3 after lung transplantation. Reducing hemolysis through improved blood-product selection and EVLP circuit management may represent a modifiable strategy to improve posttransplant outcomes.

Background: Normothermic machine perfusion (NMP) is an emerging strategy for pediatric liver transplantation, but pediatric‐specific viability criteria remain undefined. Lactate clearance, extrapolated from adult protocols, is a central marker of allograft function. In our pediatric NMP (pNMP) experience, we observed a novel pattern: initial clearance followed by secondary rise, termed rebound lactic acidosis. Methods: We retrospectively reviewed pediatric liver allografts preserved on the TransMedics Organ Care System at two centers (January 2025 through June 2026). After excluding donors > 35 kg, 18 perfusions (17 transplants) were classified as rebound lactic acidosis (lactate rise > 0.5 mmol/L after initial clearance) or sustained clearance. Rebound cases were characterized by lactate kinetics, perfusion parameters, acid–base status, bile production, histology, and recipient outcomes. Results: Six allografts demonstrated rebound, with onset 1.0–6.6 h into perfusion. All sustained bile production throughout perfusion. Circuit alkalosis temporally correlated with rebound in three cases and improved with gas flow reduction. The first allograft was discarded; the remaining five were transplanted, including one perfused for 35.5 h. Recipients had elevated POD1 transaminases and INR that normalized by POD7; three are discharged home and two remain hospitalized, all with functioning allografts (follow‐up up to 312 days). Conclusions: Rebound lactic acidosis during pNMP may not indicate allograft nonviability and may be ameliorated by modifying circuit perfusion or pH. Lactate kinetics should be interpreted within a multiparametric viability framework incorporating perfusion adequacy, acid–base status, bile production, liver function, and histology. Pediatric‐specific criteria are needed to safely expand the donor pool.