The contribution of airway and lung tissue ischemia to primary graft dysfunction.
OBJECTIVE
Primary graft dysfunction (PGD) is the primary obstacle to short-term survival for post-lung transplant patients. PGD is a form of acute lung injury secondary to donor brain death and ischemia-reperfusion damage to the allograft affecting 10-25% of all lung transplant recipients. This article reviews the significant role of allograft ischemia in the phenotypic presentation of PGD and the evidence for activation and disruption of normal cellular pathways for the development and long-term sequelae.


RESULTS
Pathways implicated in the pathogenesis of PGD resultant from tissue ischemia include abnormalities in coagulation and fibrinolysis, epithelial cell injury, endothelial cell dysfunction, chemotaxis, and alterations in cell adhesion. Blood and bronchoalveolar lavage fluid biomarkers from these pathways have been increasingly identified as useful for diagnosing and predicting the development of severe PGD.


CONCLUSIONS
Future efforts at preventing and treating severe PGD should focus on techniques for altering the pathways involved in PGD pathogenesis. Ex-vivo lung perfusion and transduction with interleukin-10 are promising modalities for preventing PGD and expanding the available lung transplant donor pool.
Diamond
Joshua M
JM
Pulmonary, Allergy, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Christie
Jason D
JD
D000818:Animals; D001777:Blood Coagulation; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects*; D055031:Primary Graft Dysfunction / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D020545:Respiratory Mucosa / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D016207:Cytokines