Alpha 1 Antitrypsin Treatment during Human Ex Vivo Lung Perfusion Improves Lung Function by Protecting Lung Endothelium

2020 ◽  
Vol 39 (4) ◽  
pp. S71-S72
Author(s):  
A. Mariscal ◽  
A. Nykanen ◽  
J. Tikkanen ◽  
A. Ali ◽  
S. Soltanieh ◽  
...  
2015 ◽  
Vol 63 (12) ◽  
pp. 645-651 ◽  
Author(s):  
Masaaki Harada ◽  
Takahiro Oto ◽  
Shinji Otani ◽  
Kentaroh Miyoshi ◽  
Masanori Okada ◽  
...  

Author(s):  
Ilker Iskender ◽  
Stephan Arni ◽  
Tatsuo Maeyashiki ◽  
Necati Citak ◽  
Mareike Sauer ◽  
...  

2020 ◽  
Vol 319 (1) ◽  
pp. L61-L70
Author(s):  
Akihiro Ohsumi ◽  
Takashi Kanou ◽  
Aadil Ali ◽  
Zehong Guan ◽  
David M. Hwang ◽  
...  

The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen ([Formula: see text]/[Formula: see text]) were observed during EVLP; however, lung compliance decreased over time in the 18-h group ( P = 0.012) and the [Formula: see text]/[Formula: see text] of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group ( P = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT.


2021 ◽  
Vol 108 (Supplement_4) ◽  
Author(s):  
J P Ehrsam ◽  
S Arni ◽  
J Chen ◽  
H Rodriguez Cetina Biefer ◽  
I Opitz ◽  
...  

Abstract Objective Ischemia-reperfusion injury compromises short- and long-term outcome after lung transplantation. The scarce existing data on the natural co-enzyme NAD+ suggest an antagonistic effect on hypoxia induced vasoconstriction, removal capacity on reactive oxygen species, and anti-inflammatory effects. We therefore investigated the impact of NAD+ on ischemic rat lungs during ex-vivo lung perfusion (EVLP). Methods Lungs were retrieved from 12 outbred Sprague Dawley male rats and exposed to 14 hours of cold ischemic storage. All lungs were then perfused in a rat EVLP system for 4 hours. Lung grafts were injected after 1, 2 and 3 hours with 2000 uM NAD + (N = 6) or placebo (N = 6) in the perfusate in proximity of the pulmonary artery. EVLP physiology and biochemistry were monitored. Results During the 4 hours of EVLP, the lung function increased significantly in the NAD+ group when compared to the placebo group. We monitored a higher vascular flow (p = 0.018), a lower mean pulmonary pressure (p = 0.007) and increased oxygenation capacity (p = 0.003). Lung compliance and weight were comparable. Tissue inflammation measured by myeloperoxidase was significantly lower in the NAD+ group (p = 0.015). In the perfusate, we observed in the NAD+ group significantly lower levels of pro-inflammatory interleukin-18 (p = 0.033) and a trend towards high levels of anti-inflammatory interleukin-10 (p = 0.080) and low levels of pro-inflammatory interleukin-12 (p = 0.146). Conclusion Findings from this preliminary study demonstrated that NAD+ is a promising agent with both anti-inflammatory properties and the ability to improve ischemic lung function. This observation should be validated in a large animal model.


Sign in / Sign up

Export Citation Format

Share Document