Article

Normothermic ex vivo perfusion prevents lung injury compared to extended cold preservation for transplantation.

Toronto Lung Transplant Program, Division of Thoracic Surgery, Latner Thoracic Laboratories, University of Toronto, Toronto, ON, Canada.
American Journal of Transplantation (impact factor: 6.39). 08/2009; 9(10):2262-9. DOI:10.1111/j.1600-6143.2009.02775.x pp.2262-9
Source: PubMed

ABSTRACT Treatment of injured donor lungs ex vivo to accelerate organ recovery and ameliorate reperfusion injury could have a major impact in lung transplantation. We have recently demonstrated a feasible technique for prolonged (12 h) normothermic ex vivo lung perfusion (EVLP). This study was performed to examine the impact of prolonged EVLP on ischemic injury. Pig donor lungs were cold preserved in Perfadex for 12 h and subsequently divided into two groups: cold static preservation (CSP) or EVLP at 37 degrees C with Steen solution for a further 12 h (total 24 h preservation). Lungs were then transplanted and reperfused for 4 h. EVLP preservation resulted in significantly better lung oxygenation (PaO(2) 531 +/- 43 vs. 244 +/- 49 mmHg, p < 0.01) and lower edema formation rates after transplantation. Alveolar epithelial cell tight junction integrity, evaluated by zona occludens-1 protein staining, was disrupted in the cell membranes after prolonged CSP but not after EVLP. The maintenance of integrity of barrier function during EVLP translates into significant attenuation of reperfusion injury and improved graft performance after transplantation. Integrity of functional metabolic pathways during normothermic perfusion was confirmed by effective gene transfer and GFP protein synthesis by lung alveolar cells. In conclusion, EVLP prevents ongoing injury associated with prolonged ischemia and accelerates lung recovery.

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    Article: Ex vivo rehabilitation of non-heart-beating donor lungs in preclinical porcine model: Delayed perfusion results in superior lung function.
    Daniel P Mulloy, Matthew L Stone, Ivan K Crosby, Damien J Lapar, Ashish K Sharma, David V Webb, Christine L Lau, Victor E Laubach, Irving L Kron
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    ABSTRACT: Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs. Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia-reperfusion injury. The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group. Uncontrolled non-heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs.
    The Journal of thoracic and cardiovascular surgery 08/2012; 144(5):1208-16. · 3.41 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

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Keywords

4 h. EVLP preservation
 
ameliorate reperfusion injury
 
barrier function
 
cold static preservation
 
donor lungs ex vivo
 
effective gene transfer
 
feasible technique
 
functional metabolic pathways
 
GFP protein synthesis
 
graft performance
 
ischemia
 
ischemic injury
 
lung alveolar cells
 
lung recovery
 
major impact
 
normothermic perfusion
 
organ recovery
 
Pig donor lungs
 
total 24 h preservation
 
zona occludens-1 protein staining
 

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