Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion†

Boffini, Massimo; Ricci, Davide; Bonato, Riccardo; Fanelli, Vito; Attisani, Matteo; Ribezzo, M.; Solidoro, Paolo; Sorbo, Lorenzo Del; Ranieri, V. Marco; Rinaldi, Mauro

doi:10.1093/ejcts/ezu239

Cited by 56 publications

(46 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistently, the synthases involved in large-sized HA polymerization were found to be up-regulated in homogenates of perfused lungs, whereas the shorter-chain HA synthase was downregulated. These observations suggest that production of high-MW HA could represent a potential mechanism that underlies the beneficial influences of EVLP observed in lung transplantation (10)(11)(12). Indeed, high-MW HA was shown to exert various protective effects in different lung injury models (22) and after orthotopic lung transplantation (27).…”

Section: Discussionmentioning

confidence: 87%

“…Recent evidence suggests that EVLP actions likely exceed evaluation/reconditioning influences. Indeed, ex vivoperfused marginal lungs demonstrated a reduced incidence of primary graft dysfunction compared with untreated standard organs (10,11). Of interest, the transplantation outcome of ex vivo-perfused optimal lungs was also improved compared with lungs subjected to standard procurement (12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Influence of ex vivo perfusion on the biomolecular profile of rat lungs

et al. 2018

View full text Add to dashboard Cite

Despite increasing clinical adoption, biologic influences of ex vivo lung perfusion (EVLP) remain insufficiently elucidated. The aim of the current study was to investigate biomolecular changes induced by EVLP in rat lungs. EVLP was maintained for 180 min. Hyaluronan, mediators, and cells were assessed in the perfusate. Gene expression, signaling pathways, and ATP content were investigated in lung tissue. EVLP induced the release of medium-high molecular weight hyaluronan and transcription of hyaluronan synthases ( P< 0.001). Increasing concentrations of inflammatory mediators were detected in the perfusate ( P < 0.001). Perfused lungs exhibited a distinctive transcriptional signature compared with organs examined before or after surgery/procurement ( P = 0.003). Up-regulated genes were involved in inflammation and its regulation, apoptosis/survival, heat shock, and oxidative stress response ( q = 0). Down-regulated genes were related to lymphocyte function ( q = 0). The NF-κB, signal transducer and activator of transcription 3, ERK1/2, p38, Akt, and stress-activated protein kinase/JNK signaling pathways were modulated by EVLP ( P < 0.05). Most of these biomolecular changes were examined and confirmed in additional experiments that were performed in lungs procured from donation after cardiocirculatory death after 180 min of warm ischemia. The current study demonstrates that EVLP broadly affects the lung biomolecular phenotype. These findings improve our comprehension of the effects exerted by the procedure and encourage additional research in preclinical models to implement therapeutic interventions.-Lonati, C., Bassani, G. A., Brambilla, D., Leonardi, P., Carlin, A., Faversani, A., Gatti, S., Valenza, F. Influence of ex vivo perfusion on the biomolecular profile of rat lungs.

show abstract

Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

Influence of ex vivo perfusion on the biomolecular profile of rat lungs

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The authors did not find any differences between the study groups in term of each grade of PGD as well as extracorporeal membrane oxygenation requirement. One interesting point in this study was the influence of EVLP on a relatively lower volume center: EVLP resulted in a 22% increase in LTx volume through a successful donor lung recondition rate of 73% .…”

Section: Clinical Experience With Evlp: State Of the Artmentioning

confidence: 98%

Ex vivo lung perfusion

Reeb

Cypel

2016

Clinical Transplantation

View full text Add to dashboard Cite

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.

show abstract

“…In a prospective non-randomized trial by the Toronto Lung Transplant Program, 15% of recipients of lungs maintained with EVLP developed PGD as compared to 30% in the control non-EVLP group (p=0.11) [33]. Another study by an Italian group showed a similar trend towards a reduction in PGD in lungs reconditioned by EVLP [34]. Since lungs can be maintained on EVLP for at least 12–24 hours, EVLP can extend the time available for assessment of donor lungs to determine suitability for transplantation [35].…”

Section: Ex Vivo Lung Perfusion and Lung Reconditioningmentioning

confidence: 99%

“…EVLP can limit the time of injurious cold ischemia, another known operative risk factor for PGD [3, 36, 37]. In early studies, despite an extended total ischemic time, EVLP has not increased the incidence of PGD [34, 38–40]. …”

Section: Ex Vivo Lung Perfusion and Lung Reconditioningmentioning

confidence: 99%

Primary graft dysfunction: pathophysiology to guide new preventive therapies

Shaver

Ware

2017

Expert Review of Respiratory Medicine

View full text Add to dashboard Cite

Introduction Primary graft dysfunction (PGD) is a common complication of lung transplantation characterized by acute pulmonary edema associated with bilateral pulmonary infiltrates and hypoxemia in the first 3 post-operative days. Development of PGD is a predictor of poor short- and long-term outcomes after lung transplantation, but there are currently limited tools to prevent its occurrence. Areas covered Several potentially modifiable donor, recipient, and operative risk factors for PGD have been identified. In addition, basic and translational studies in animals and ex vivo lung perfusion systems have identified several biomarkers and mechanisms of injury in PGD. In this review, we outline the clinical and genetic risk factors for PGD and summarize experimental data exploring PGD mechanisms, with a focus on strategies to reduce PGD risk and on potential novel molecular targets for PGD prevention. Expert commentary Because of the clinical importance of PGD, development of new therapies for prevention and treatment is critically important. Improved understanding of the pathophysiology of clinical PGD provides a framework to explore novel agents to prevent or reverse PGD. Ex vivo lung perfusion provides a new opportunity for rapid development of therapeutics that target this devastating complication of lung transplantation.

show abstract

Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion†

Cited by 56 publications

References 16 publications

Influence of ex vivo perfusion on the biomolecular profile of rat lungs

Influence of ex vivo perfusion on the biomolecular profile of rat lungs

Ex vivo lung perfusion

Primary graft dysfunction: pathophysiology to guide new preventive therapies

Contact Info

Product

Resources

About