Physiologic and Epigenetic Changes with Pulmonary Vascular Injury After Lung Transplantation

  • Steven Kenneth HuangEmail author
  • Roberto G. Carbone
  • Giovanni Bottino


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.


Ischemia-reperfusion injury Primary graft dysfunction Reimplantation injury Bronchiolitis obliterans Ex vivo lung perfusion Reactive oxygen species Oxidative stress Epigenetics DNA methylation Histone modification 



Acute respiratory distress syndrome


Bronchiolitis obliterans syndrome


Chronic obstructive pulmonary disease


DNA methyltransferase


Extracorporeal membrane oxygenation


Ex vivo lung perfusion


Hypoxia-inducible factor








Neutrophil extracellular trap


Nitric oxide


Platelet-activating factor


Primary graft dysfunction


Reactive oxygen species


Ten-eleven translocation


Toll-like receptor


Tumor necrosis factor


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Copyright information

© The Author(s) 2018

Authors and Affiliations

  • Steven Kenneth Huang
    • 1
    Email author
  • Roberto G. Carbone
    • 2
  • Giovanni Bottino
    • 3
  1. 1.Department of Pulmonary and Critical Care MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Department of Internal MedicineUniversity of GenoaGenoaItaly
  3. 3.Department of MedicineUniversity of Genoa—DIMIGenoaItaly

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