Transplant Suitability of Rejected Human Donor Lungs With Prolonged Cold Ischemia Time in Low-Flow Acellular and High-Flow Cellular Ex Vivo Lung Perfusion Systems

2019 ◽  
Vol 103 (9) ◽  
pp. 1799-1808 ◽  
Author(s):  
Toshihiro Okamoto ◽  
David Wheeler ◽  
Carol F. Farver ◽  
Kenneth R. McCurry
2014 ◽  
Vol 186 (2) ◽  
pp. 600
Author(s):  
A. Ardehali ◽  
O. Proceed II ◽  
M. Deng

2013 ◽  
Vol 32 (4) ◽  
pp. S156
Author(s):  
M. Deng ◽  
E. Soltesz ◽  
E. Hsich ◽  
Y. Naka ◽  
D. Mancini ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Aleksandra Leligdowicz ◽  
James T. Ross ◽  
Nicolas Nesseler ◽  
Michael A. Matthay

Abstract Background The ex vivo human perfused lung model has enabled optimizing donor lungs for transplantation and delineating mechanisms of lung injury. Perfusate and airspace biomarkers are a proxy of the lung response to experimental conditions. However, there is a lack of studies evaluating biomarker kinetics during perfusion and after exposure to stimuli. In this study, we analyzed the ex vivo-perfused lung response to three key perturbations: exposure to the perfusion circuit, exogenous fresh whole blood, and bacteria. Results Ninety-nine lungs rejected for transplantation underwent ex vivo perfusion. One hour after reaching experimental conditions, fresh whole blood was added to the perfusate (n = 55). Two hours after reaching target temperature, Streptococcus pneumoniae was added to the perfusate (n = 42) or to the airspaces (n = 17). Perfusate and airspace samples were collected at baseline (once lungs were equilibrated for 1 h, but before blood or bacteria were added) and 4 h later. Interleukin (IL)-6, IL-8, angiopoietin (Ang)-2, and soluble tumor necrosis factor receptor (sTNFR)-1 were quantified. Baseline perfusate and airspace biomarker levels varied significantly, and this was not related to pre-procurement PaO2:FiO2 ratio, cold ischemia time, and baseline alveolar fluid clearance (AFC). After 4 h of ex vivo perfusion, the lung demonstrated a sustained production of proinflammatory mediators. The change in biomarker levels was not influenced by baseline donor lung characteristics (cold ischemia time, baseline AFC) nor was it associated with measures of experimental epithelial (final AFC) or endothelial (percent weight gain) injury. In the presence of exogenous blood, the rise in biomarkers was attenuated. Lungs exposed to intravenous (IV) bacteria relative to control lungs demonstrated a significantly higher rise in perfusate IL-6. Conclusions The ex vivo-perfused lung has a marked endogenous capacity to produce inflammatory mediators over the course of short-term perfusion that is not significantly influenced by donor lung characteristics or the presence of exogenous blood, and only minimally affected by the introduction of systemic bacteremia. The lack of association between biomarker change and donor lung cold ischemia time, final alveolar fluid clearance, and experimental percent weight gain suggests that the maintained ability of the human lung to produce biomarkers is not merely a marker of lung epithelial or endothelial injury, but may support the function of the lung as an immune cell reservoir.


2020 ◽  
Author(s):  
Aleksandra Leligdowicz ◽  
James T. Ross ◽  
Nicolas Nesseler ◽  
Michael A. Matthay

Abstract Background The ex vivo human perfused lung model has enabled optimizing donor lungs for transplantation and delineating mechanisms of lung injury. Perfusate and airspace biomarkers are a proxy of the lung response to experimental conditions. However, there is a lack of studies evaluating biomarker kinetics during perfusion and after exposure to stimuli. In this study we analyzed the ex vivo perfused lung response to three key perturbations: exposure to the perfusion circuit, exogenous fresh whole blood, and bacteria. Results 99 lungs rejected for transplantation underwent ex vivo perfusion. One hour after reaching experimental conditions, fresh whole blood was added to the perfusate (n=55). Two hours after reaching target temperature, Streptococcus pneumoniae was added to the perfusate (n=42) or to the airspaces (n=17). Perfusate and airspace samples were collected at baseline (once lungs were equilibrated for 1 hour, but before blood or bacteria were added) and 4 hours later. Interleukin (IL)-6, IL-8, Angiopoietin (Ang)-2, and soluble tumor necrosis factor receptor (sTNFR)-1 were quantified. Baseline perfusate and airspace biomarker levels varied significantly, and this was not related to pre-procurement PaO2:FiO2 ratio, cold ischemia time, and baseline alveolar fluid clearance (AFC). After 4 hours of ex vivo perfusion, the lung demonstrated a sustained production of proinflammatory mediators. The change in biomarker levels was not influenced by baseline donor lung characteristics (cold ischemia time, baseline AFC) nor was it associated with measures of experimental epithelial (final AFC) or endothelial (percent weight gain) injury. In the presence of exogenous blood, the rise in biomarkers was attenuated. Lungs exposed to intravenous (IV) bacteria relative to control lungs demonstrated a significantly higher rise in perfusate IL-6. Conclusions The ex vivo perfused lung has a marked endogenous capacity to generate inflammatory responses over the course of short-term perfusion. The lack of association between biomarker change and donor lung cold ischemia time as well as final alveolar fluid clearance and experimental percent weight gain suggests that the maintained ability to produce biomarkers is not merely a marker of lung epithelial or endothelial injury but may support the lung’s role as an immune cell reservoir.


2020 ◽  
Author(s):  
Aleksandra Leligdowicz ◽  
James T. Ross ◽  
Nicolas Nesseler ◽  
Michael A. Matthay

Abstract Background: The ex vivo human perfused lung model has enabled optimizing donor lungs for transplantation and delineating mechanisms of lung injury. Perfusate and airspace biomarkers are a proxy of the lung response to experimental conditions. However, there is a lack of studies evaluating biomarker kinetics during perfusion and after exposure to stimuli. In this study we analyzed the ex vivo perfused lung response to three key perturbations: exposure to the perfusion circuit, exogenous fresh whole blood, and bacteria.Results: 99 lungs rejected for transplantation underwent ex vivo perfusion. One hour after reaching experimental conditions, fresh whole blood was added to the perfusate (n=55). Two hours after reaching target temperature, Streptococcus pneumoniae was added to the perfusate (n=42) or to the airspaces (n=17). Perfusate and airspace samples were collected at baseline (once lungs were equilibrated for 1 hour, but before blood or bacteria were added) and 4 hours later. Interleukin (IL)-6, IL-8, Angiopoietin (Ang)-2, and soluble tumor necrosis factor receptor (sTNFR)-1 were quantified. Baseline perfusate and airspace biomarker levels varied significantly, and this was not related to pre-procurement PaO2:FiO2 ratio, cold ischemia time, and baseline alveolar fluid clearance (AFC). After 4 hours of ex vivo perfusion, the lung demonstrated a sustained production of proinflammatory mediators. The change in biomarker levels was not influenced by baseline donor lung characteristics (cold ischemia time, baseline AFC) nor was it associated with measures of experimental epithelial (final AFC) or endothelial (percent weight gain) injury. In the presence of exogenous blood, the rise in biomarkers was attenuated. Lungs exposed to intravenous (IV) bacteria relative to control lungs demonstrated a significantly higher rise in perfusate IL-6.Conclusions: The ex vivo perfused lung has a marked endogenous capacity to produce inflammatory mediators over the course of short-term perfusion that is not significantly influenced by donor lung characteristics or the presence of exogenous blood, and only minimally affected by the introduction of systemic bacteremia. The lack of association between biomarker change and donor lung cold ischemia time, final alveolar fluid clearance, and experimental percent weight gain suggest that the maintained ability of the human lung to produce biomarkers is not merely a marker of lung epithelial or endothelial injury, but may support the function of the lung as an immune cell reservoir.


2019 ◽  
Vol 38 (4) ◽  
pp. S321
Author(s):  
H. Niikawa ◽  
T. Okamoto ◽  
K.S. Ayyat ◽  
Y. Itoda ◽  
C.F. Farver ◽  
...  

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