Primary graft dysfunction after lung transplantation

Hunt, Mallory; Cantu, Edward

doi:10.1097/mot.0000000000001065

Cited by 4 publications

(8 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lung I/R injury following lung transplantation may precipitate primary graft dysfunction, with significant short- and long-term consequences ( 23 ). A hallmark of I/R injury is endothelial damage and dysfunction, resulting in the loss of endothelial barrier function, high permeability edema, vasoactive imbalance, procoagulant activity and the recruitment and activation of inflammatory leukocytes ( 4 – 6 ).…”

Section: Discussionmentioning

confidence: 99%

Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion

Parapanov,

Debonneville,

Allouche

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

IntroductionThe pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that treating damaged rat lungs by a transient heat stress during ex-vivo lung perfusion (EVLP) to elicit a pulmonary heat shock response could protect the endothelium from severe reperfusion injury.MethodsRat lungs damaged by 1h warm ischemia were reperfused on an EVLP platform for up to 6h at a constant temperature (T°) of 37°C (EVLP37°C group), or following a transient heat stress (HS) at 41.5°C from 1 to 1.5h of EVLP (EVLPHS group). A group of lungs exposed to 1h EVLP only (pre-heating conditions) was added as control (Baseline group). In a first protocol, we measured lung heat sock protein expression (HSP70, HSP27 and Hsc70) at selected time-points (n=5/group at each time). In a second protocol, we determined (n=5/group) lung weight gain (edema), pulmonary compliance, oxygenation capacity, pulmonary artery pressure (PAP) and vascular resistance (PVR), the expression of PECAM-1 (CD31) and phosphorylation status of Src-kinase and VE-cadherin in lung tissue, as well as the release in perfusate of cytokines (TNFα, IL-1β) and endothelial biomarkers (sPECAM, von Willebrand Factor -vWF-, sE-selectin and sICAM-1). Histological and immunofluorescent studies assessed perivascular edema and formation of 3-nitrotyrosine (a marker of peroxinitrite) in CD31 lung endothelium.ResultsHS induced an early (3h) and persisting expression of HSP70 and HSP27, without influencing Hsc70. Lungs from the EVLP37°C group developed massive edema, low compliance and oxygenation, elevated PAP and PVR, substantial release of TNFα, IL-1β, s-PECAM, vWF, E-selectin and s-ICAM, as well as significant Src-kinase activation, VE-cadherin phosphorylation, endothelial 3-NT formation and reduced CD31 expression. In marked contrast, all these alterations were either abrogated or significantly attenuated by HS treatment.ConclusionThe therapeutic application of a transient heat stress during EVLP of damaged rat lungs reduces endothelial permeability, attenuates pulmonary vasoconstriction, prevents src-kinase activation and VE-cadherin phosphorylation, while reducing endothelial peroxinitrite generation and the release of cytokines and endothelial biomarkers. Collectively, these data demonstrate that therapeutic heat stress may represent a promising strategy to protect the lung endothelium from severe reperfusion injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion

Parapanov,

Debonneville,

Allouche

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Early grade 3 PGD patients are characterized by a decrease in the diversity of the lung flora. This dynamic change in turn triggers inflammatory signals that lead to the development of severe PGD 20 . In addition to the altered flora diversity, the lungs of patients with PGD grade 3 are enriched in a number of specific flora, such as the genera Modestobacter, Scardovia and Selenomonas and the species Modestobacter marinus and Scardovia wiggsiae.…”

Section: Discussionmentioning

confidence: 99%

The role of lung microbiota in primary graft dysfunction in lung transplant recipients

Wu,

Huang,

et al. 2023

Clinical Transplantation

View full text Add to dashboard Cite

BackgroundRecent studies have shown that the lung microbiota is altered in critically ill patients and predicts clinical outcomes. Primary graft dysfunction (PGD) is a common complication and a leading cause of death within 1 month of lung transplantation, but the clinical significance of changes in the lung bacterial community during PGD is unclear. The aim of this study was to determine the contribution of the lung microbiota to the development and course of severe PGD.MethodsWe conducted a retrospective study to characterize the lung microbiota of 32 lung transplant patients with combined PGD using next‐generation sequencing of bronchoalveolar lavage samples. The relationship between lung flora dysbiosis and lung immunity in PGD was assessed by quantification of alveolar cytokines. The contribution of microbiota characteristics to patient outcomes was assessed by estimating overall survival.ResultsPatients diagnosed with PGD grade 3 showed a reduction in alpha diversity, driven by a significant increase in the abundance of the genera Modestobacter, Scardovia and Selenomonas, and a reduction in the proportion of the genera Klebsiella and Oribacterium. Alpha diversity of the lung microbiota in PGD3 patients was negatively correlated with BALF interleukin (IL)‐2 (r = ‐.752, p < .05). In addition, bacterial diversity in the lung microbiota of non‐survivors was lower than that of survivors (p = .041).ConclusionsThere is variation in the lung microbiota of PGD grade 3 patients and dysbiosis of the lung microbiota is associated with lung immunity. The lung microbiota has potential in the diagnosis and treatment of PGD grade 3.

show abstract

“…Proinflammatory mechanisms at the time of reperfusion trigger endothelial and alveolar injury, cellular activation and edema. Indeed, bronchoalveolar and tissue levels of the neutrophil chemoattractant IL-6, 8 and 10 correlate with PGD severity and mortality [44]. Risk factors for PGD include African-American race, female sex, history of smoking, positive sputum culture and head trauma [44].…”

Section: Postoperative Supportmentioning

confidence: 99%

ECMO utilization in lung transplantation

Asija,

Flatley,

Kanade

et al. 2024

Evolving Therapies and Technologies in Extracorporeal Membrane Oxygenation [Working Title]

View full text Add to dashboard Cite

Extracorporeal membrane oxygenation (ECMO) is a mechanical device that supports or replaces heart and lung function. It has been implemented with increasing effectiveness as a bridge to lung transplant in lung transplant candidates who fail maximum medical management. Depending on the physiologic needs of the patient, various ECMO strategies can be implemented and modified as the patient’s clinical condition evolves. ECMO can also be used as an intraoperative adjunct to manage poorly tolerated single-lung ventilation or elevated pulmonary artery pressures. ECMO in the post-operative setting can also be used to minimize ventilator injury in the face of primary graft dysfunction (PGD) as well as to prevent development of pulmonary edema. This chapter will describe ECMO physiology and configurations along with bridge and support strategies used in lung transplantation.

show abstract

Primary graft dysfunction after lung transplantation

Cited by 4 publications

References 59 publications

Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion

Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion

The role of lung microbiota in primary graft dysfunction in lung transplant recipients

ECMO utilization in lung transplantation

Contact Info

Product

Resources

About