Abstract

Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure. However, ischemia–reperfusion injury (IRI) inevitably occurs after lung transplantation. The most severe form of IRI leads to primary graft failure, which is an important cause of morbidity and mortality after lung transplantation. IRI may also induce rejection, which is the main cause of mortality in recipients. Despite advances in donor management and graft preservation, most donor grafts are still unsuitable for transplantation. Although the pulmonary endothelium is the primary target site of IRI, the pathophysiology of lung IRI remains incompletely understood. It is essential to understand the mechanism of pulmonary IRI to improve the outcomes of lung transplantation. Therefore, we reviewed the state-of-the-art in the management of pulmonary IRI after lung transplantation. Recently, the ex vivo lung perfusion (EVLP) system has been clinically introduced worldwide. Various promising therapeutic strategies for the protection of the endothelium against IRI, including EVLP, inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, and mesenchymal stromal cell therapy, are awaiting clinical application. We herein review the latest advances in the field of pulmonary IRI in lung transplantation.

Highlights

  • Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure

  • ischemia–reperfusion injury (IRI) after lung transplantation is the main reason for primary graft dysfunction (PGD), which is a major cause of mortality and morbidity in the postoperative period

  • Because IRI-induced PGD and donor shortage are more common in lung transplantation than in the transplantation of other organs, the development of a highly effective and reliable organ preservation solution would contribute to improving the function of transplanted organs and to alleviating the shortage of donor organs by enabling the use of marginal donor lungs [3,4]

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Summary

Kalyuzhny

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. It is essential to understand the mechanism of lung IRI for its prevention and treatment. We discuss the underlying mechanisms of pulmonary IRI related to lung transplantation

Clinical Dilemma in Lung Transplantation
Ischemia–Reperfusion Injury
Changes in Ischemic Storage
Consequences of Ischemia–Reperfusion
Scheme
Strategies to Prevent Ischemia–Reperfusion Injury
Donor and Recipient Factors
Procurement and Preservation
Protection in Reperfusion and Ventilation
Donation after Cardiac Death and Ischemia-Reperfusion Injury
Current Therapies and Promising Future Possibilities
Ex Vivo Lung Perfusion
Novel Strategies for Endothelial Protection
Surfactants
Inhaled Beta-2 Adrenoreceptor Agonists
Therapeutic Gases
Fibrinolytic Treatment
Mesenchymal Stem Cells
Findings
Conclusions
Full Text
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