The role of the endothelin-1 pathway as a biomarker for donor lung assessment in clinical ex vivo lung perfusion.

Abstract

BACKGROUND:

Normothermic ex vivo lung perfusion (EVLP) is a preservation technique that allows reassessment of donor lungs before transplantation. We hypothesized that the endothelin-1 (ET-1) axis would be associated with donor lung performance during EVLP and recipient outcomes after transplantation.

METHODS:

ET-1, Big ET-1, endothelin-converting enzyme (ECE), and nitric oxide (NO) metabolites were quantified in the perfusates of donor lungs enrolled in a clinical EVLP trial. Lungs were divided into 3 groups: (I) Control: bilateral transplantation with good early outcomes defined as absence of primary graft dysfunction (PGD) Grade 3 (PGD3) ; (II) PGD3: bilateral lung transplantation with PGD3 any time within 72 hours; and (III) Declined: lungs rejected after EVLP.

RESULTS:

There were 25 lungs in Group I, 7 in Group II, and 16 in Group III. At 1 and 4 hours of EVLP, the perfusates of Declined lungs had significantly higher levels of ET-1 (3.1 ± 2.1 vs. 1.8±2.3 pg/ml, p = 0.01; 2.7 ± 2.2 vs. 1.3 ± 1.1 pg/ml, p = 0.007) and Big ET-1 (15.8 ± 14.2 vs. 7.0 ± 6.5 pg/ml, p = 0.001; 31.7 ± 17.4 vs. 19.4 ± 9.5 pg/ml, p = 0.007) compared with Controls. Nitric oxide metabolite concentrations were significantly higher in Declined and PGD3 lungs than in Controls. For cases of donation after cardiac death, PGD3 and Declined lungs had higher ET-1 and Big ET-1 levels at 4 hours of perfusion compared with Controls. At this time point, Big ET-1 had excellent accuracy to distinguish PGD3 (96%) and Declined (92%) from Control lungs.

CONCLUSIONS:

In donation after cardiac death lungs, perfusate ET-1 and Big ET-1 are potential predictors of lung function during EVLP and after lung transplantation. They were also associated with non-use of lungs after EVLP and thus could represent useful biomarkers to improve the accuracy of donor lungs selection.

• Authors: Tiago Noguchi Machuca, Marcelo Cypel, Yidan Zhao, Hartmut Grasemann, Farshad Tavasoli, Jonathan C Yeung, Riccardo Bonato, Manyin Chen, Ricardo Zamel, Yi-Min Chun, Zehong Guan, Marc de Perrot, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 34 Issue 6 Pg. 849-57 (Jun 2015) ISSN: 1557-3117 [Electronic] United States
• PMID: 25907141 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Endothelin-1
• Nitric Oxide
• Aspartic Acid Endopeptidases
• Metalloendopeptidases
• Endothelin-Converting Enzymes

Topics

• Adult
• Aspartic Acid Endopeptidases (metabolism)
• Biomarkers (metabolism)
• Endothelin-1 (metabolism)
• Endothelin-Converting Enzymes
• Female
• Graft Rejection (epidemiology)
• Humans
• Incidence
• Lung (metabolism)
• Lung Transplantation
• Male
• Metalloendopeptidases (metabolism)
• Middle Aged
• Nitric Oxide (metabolism)
• Perfusion (methods)
• Predictive Value of Tests
• Respiratory Insufficiency (surgery)
• Retrospective Studies
• Signal Transduction (physiology)
• Time Factors
• Tissue and Organ Procurement (standards)
• Transplant Recipients
• Treatment Outcome