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Physiologic and Epigenetic Changes with Pulmonary Vascular Injury After Lung Transplantation

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Lung Transplantation

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Abstract

Despite advances in donor procurement, storage, and surgical reimplantation techniques, the development of ischemia-reperfusion injury in the first 48–72 h after transplantation remains a significant cause of morbidity and mortality. With more severe forms of injury, primary graft dysfunction can occur. Risk factors for vascular injury include the condition of the donor, duration of cold ischemia time, and factors associated with the recipient and management posttransplantation. The pathophysiology of ischemia-reperfusion injury is complex and involves the dysregulation of energy metabolism and accompanying apoptosis, oxidative stress with reactive oxygen species, and endothelial barrier dysfunction. The release of cytokines and bioactive lipid mediators also plays an important role in the process. Further recruitment of neutrophils and T cells contribute to further damage. Although evidence for epigenetic changes occurring after reperfusion injury is sparse, the physiologic alterations after transplantation provides an environment for epigenetic changes to occur in a fashion similar to that observed in many other forms of lung disease such as pulmonary fibrosis, asthma, and chronic obstructive lung disease. Strategies to limit ischemia-reperfusion include use of formulated preservation solutions, limitation of cold ischemia time, and use of ex vivo lung perfusion strategies. Although treatment remains largely supportive, therapies that target certain pathophysiologic pathways have achieved particular interest.

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Abbreviations

ARDS:

Acute respiratory distress syndrome

BOS:

Bronchiolitis obliterans syndrome

COPD:

Chronic obstructive pulmonary disease

DNMT:

DNA methyltransferase

ECMO:

Extracorporeal membrane oxygenation

EVLP:

Ex vivo lung perfusion

HIF:

Hypoxia-inducible factor

IFN:

Interferon

IL:

Interleukin

miRNA:

MicroRNA

NET:

Neutrophil extracellular trap

NO:

Nitric oxide

PAF:

Platelet-activating factor

PGD:

Primary graft dysfunction

ROS:

Reactive oxygen species

TET:

Ten-eleven translocation

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

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Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA

    Steven Kenneth Huang

  2. Department of Internal Medicine, University of Genoa, Genoa, Italy

    Roberto G. Carbone

  3. Department of Medicine, University of Genoa—DIMI, Genoa, Italy

    Giovanni Bottino

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  1. Steven Kenneth Huang
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  2. Roberto G. Carbone
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Correspondence to Steven Kenneth Huang .

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  1. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine University of Washington, Seattle, Washington, USA

    Ganesh Raghu

  2. Department of Internal Medicine, University of Genoa, Genoa, Italy

    Roberto G. Carbone

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Huang, S.K., Carbone, R.G., Bottino, G. (2018). Physiologic and Epigenetic Changes with Pulmonary Vascular Injury After Lung Transplantation. In: Raghu, G., Carbone, R. (eds) Lung Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-91184-7_10

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