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

Machuca, Tiago; Cypel, Marcelo; Zhao, Yidan; Grasemann, Hartmut; Tavasoli, Farshad; Yeung, Jonathan C.; Bonato, Riccardo; Chen, Manyin; Zamel, R.; Chun, Yi-Min; Guan, Z.; Perrot, Marc de; Waddell, Thomas K.; Liu, Mingyao; Keshavjee, Shaf

doi:10.1016/j.healun.2015.01.003

Cited by 46 publications

(46 citation statements)

References 23 publications

(30 reference statements)

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“…This could be further elaborated using a biomarker for lung acceptance such as endothelin 1 (15) and interleukin-1b/tumor necrosis factora (16), which are already being proposed, among others, as promising markers. This could be used to relate the rather subjective CT findings to a quantifiable parameter that might aid in further decision-making.…”

Section: Discussionmentioning

confidence: 99%

“…This could be used to relate the rather subjective CT findings to a quantifiable parameter that might aid in further decision-making. This could be further elaborated using a biomarker for lung acceptance such as endothelin 1 (15) and interleukin-1b/tumor necrosis factora (16), which are already being proposed, among others, as promising markers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Radiological Analysis of Unused Donor Lungs: A Tool to Improve Donor Acceptance for Transplantation?

Verleden

Martens

Ordies

et al. 2017

American Journal of Transplantation

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Despite donor organ shortage, a large proportion of possible donor lungs are declined for transplantation. Criteria for accepting/declining lungs remain controversial because of the lack of adequate tools to aid in decision-making. We collected, air-inflated, and froze a large series of declined/unused donor lungs and subjected these lung specimens to CT examination. Affected target regions were scanned by using micro-CT. Lungs from 28 donors were collected. Two lungs were unused, six were declined for non-allograft-related reasons (collectively denominated nonallograft declines, n = 8), and 20 were declined because of allograft-related reasons. CT scanning demonstrated normal lung parenchyma in only four of eight nonallograft declines, while relatively normal parenchyma was found in 12 of 20 allograft-related declines. CT and micro-CT examinations confirmed the reason for decline in most lungs and revealed unexpected (unknown from clinical files or physical inspection) CT abnormalities in other lungs. CT-based measurements showed a higher mass and density in the lungs with CT alterations compared with lungs without CT abnormalities. CT could aid in the decision-making to accept or decline donor lungs which could lead to an increase in the quantity and quality of lung allografts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Radiological Analysis of Unused Donor Lungs: A Tool to Improve Donor Acceptance for Transplantation?

Verleden

Martens

Ordies

et al. 2017

American Journal of Transplantation

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“…There is further data to suggest that EVLP has both the potential for benefit and harm, as seen by an increase in inflammation observed during EVLP . There are also ongoing investigations looking for further prognosticating parameters during EVLP to predict quality post‐transplantation, including biomarkers . The pragmatic concerns with biomarker analysis is often related to the time lag between sampling and test results, which does not allow for real‐time clinical decision making to be impacted by most associative biomarker studies .…”

Section: Discussionmentioning

confidence: 99%

A Decrease in Hypoxic Pulmonary Vasoconstriction Correlates With Increased Inflammation During Extended Normothermic Ex Vivo Lung Perfusion

et al. 2017

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Normothermic ex vivo lung perfusion (EVLP) is an evolving technology to evaluate function of donor lungs to determine suitability for transplantation. We hypothesize that hypoxic pulmonary vasoconstriction (HPV) during EVLP will provide a more sensitive parameter of lung function to determine donor lung quality for lung transplantation. Eight porcine lungs were procured, and subsequently underwent EVLP with autologous blood and STEEN solution for 10 h. Standard physiologic parameters including dynamic compliance, peak airway pressure, and pulmonary vascular resistance (PVR) remained stable (P = 0.055), mean oxygenation (PO /FiO ) was 400 ± 18 mm Hg on average throughout perfusion. Response to hypoxia resulted in a robust increase in PVR (ΔPVR) up to 4 h of perfusion, however the HPV response then blunted beyond T6 (P < 0.01). The decrease in HPV response inversely correlated to cytokine concentrations of Interleukin-6 and tumor necrosis factor-α (P < 0.01). Despite acceptable lung oxygenation and standard physiologic parameters during 10 h of EVLP, there is a subclinical deterioration of lung function. HPV challenges can be performed during EVLP as a simple and more sensitive index of pulmonary vascular reactivity.

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“…The best biomarker to differentiate declined lungs from control lungs was stem cell growth factor‐β (p < 0.001; area under the curve (AUC) = 0.86), whereas the best markers to differentiate PGD grade‐3 from control cases were interleukin‐8 (p < 0.001; AUC = 0.93) and growth‐regulated oncogen‐α (p = 0.001; AUC = 0.89) . A contemporary paper also published by the Toronto group and using the same study design identified big endothelin‐1 as a biomarker of PGD grade‐3 lungs (control group vs. PGD group; p = 0.01; AUC = 0.96) and EVLP‐assessed lungs declined for LTx (control group vs. declined group; p = 0.003; AUC = 0.92) .…”

Section: Evlp: the Futurementioning

confidence: 94%

Ex vivo lung perfusion

Reeb

Cypel

2016

Clinical Transplantation

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Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

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

Cited by 46 publications

References 23 publications

Radiological Analysis of Unused Donor Lungs: A Tool to Improve Donor Acceptance for Transplantation?

Radiological Analysis of Unused Donor Lungs: A Tool to Improve Donor Acceptance for Transplantation?

A Decrease in Hypoxic Pulmonary Vasoconstriction Correlates With Increased Inflammation During Extended Normothermic Ex Vivo Lung Perfusion

Ex vivo lung perfusion

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