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

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Objectives 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)1208-1216
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume144
Issue number5
DOIs
StatePublished - Nov 2012
Externally publishedYes

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Swine
Rehabilitation
Perfusion
Tissue Donors
Lung
Warm Ischemia
Transplantation
Purinergic P1 Receptor Agonists
Oxygen
Transplants
Pressure
Cefazolin
Partial Pressure
Methylprednisolone
Touch
Blood Donors
Interleukin-8
Interleukin-1
Pulmonary Artery
Reperfusion

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Ex vivo rehabilitation of non–heart-beating donor lungs in preclinical porcine model : Delayed perfusion results in superior lung function. / Mulloy, Daniel P.; Stone, Matthew L.; Crosby, Ivan K.; LaPar, Damien J.; Sharma, Ashish K.; Webb, David V.; Lau, Christine L.; Laubach, Victor E.; Kron, Irving L.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 144, No. 5, 11.2012, p. 1208-1216.

Research output: Contribution to journalArticle

Mulloy, Daniel P. ; Stone, Matthew L. ; Crosby, Ivan K. ; LaPar, Damien J. ; Sharma, Ashish K. ; Webb, David V. ; Lau, Christine L. ; Laubach, Victor E. ; Kron, Irving L. / Ex vivo rehabilitation of non–heart-beating donor lungs in preclinical porcine model : Delayed perfusion results in superior lung function. In: Journal of Thoracic and Cardiovascular Surgery. 2012 ; Vol. 144, No. 5. pp. 1208-1216.
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abstract = "Objectives 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. Methods 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. Results 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. Conclusions 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.",
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AU - LaPar, Damien J.

AU - Sharma, Ashish K.

AU - Webb, David V.

AU - Lau, Christine L.

AU - Laubach, Victor E.

AU - Kron, Irving L.

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