Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate are associated with primary graft dysfunction after human lung transplantation
| Autor: | Marcelo Cypel, K. Hashimoto, Tomohito Saito, Hyunhee Kim, Tiago N. Machuca, Thomas K. Waddell, Stephen C. Juvet, Mingyao Liu, Michael Hsin, Shaf Keshavjee, Ricardo Zamel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine medicine.medical_specialty Pathology medicine.medical_treatment Urology Primary Graft Dysfunction Inflammation 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Fraction of inspired oxygen medicine Lung transplantation Transplantation Lung business.industry respiratory system 030104 developmental biology medicine.anatomical_structure Apoptosis Surgery medicine.symptom Cardiology and Cardiovascular Medicine business Ex vivo |
| Zdroj: | The Journal of Heart and Lung Transplantation. 37:240-249 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2017.06.005 |
| Popis: | Ex vivo lung perfusion (EVLP) enables assessment of marginal donor lungs for transplantation, with similar clinical outcomes to conventional lung transplantation. We investigated whether cell death-related proteins in the EVLP perfusate could predict primary graft dysfunction (PGD) after transplantation.M30 (indicating epithelial apoptosis), M65 (indicating total epithelial cell death), and high mobility group box 1 (HMGB-1, related to cell death and inflammation) protein levels in EVLP perfusate were measured by enzyme-linked immunosorbent assay and correlated with clinical outcomes.From 100 sequential EVLP patients, 79 lungs were transplanted. Patients who were bridged with extracorporeal life support (ECLS, n = 6) or who received lobar/single lung (n = 25) were excluded. PGD grade 3 (partial pressure of arterial oxygen/fraction of inspired oxygen200 or need for ECLS) developed in 11 at any time within 72 hours after transplantation (PGD Group). PGD grade 3 did not develop in 34 patients (Control Group). M30 was significantly higher in the PGD Group than in the Control Group at 1 hour (PGD: 73.3 ± 24.9, control: 53.9 ± 15.9 U/liter; p0.01) and at 4 hours (PGD: 137.0 ± 146.6, Control: 72.4 ± 40.0 U/liter; p = 0.046) of EVLP. The increase of HMGB-1 from 1 to 4 hours of EVLP was significantly greater in the PGD Group (PGD: 37.0 ± 25.4, Control: 7.2 ± 16.8 ng/ml; p0.001). Higher levels of or a greater increase in M30 and a greater increase in HMGB-1 were associated with higher mortality in Cox regression.Levels of M30 and HMGB-1 in the EVLP perfusate correlate with PGD after lung transplantation and might therefore be useful biomarkers to improve donor lung assessment during EVLP. |
| Databáze: | OpenAIRE |
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