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LETTER TO EDITOR
Ex Vivo Lung Perfusion Using Whole Blood: How?

Dear Editor:

The ex vivo lung perfusion (EVLP) procedure has emerged and established itself as a safe and reliable method for the reconditioning of marginal lung grafts. Many clinical centers worldwide have reported the successful and valuable application of this procedure.1 Preclinical studies have continued further investigations and refining of the technology. One of the main points of discussion and controversy is the nature of the used perfusate, whether it should be whole blood, acellular perfusate, or a mixture of red blood cells and acellular perfusate. Although each point of view has advantages and disadvantages, some published studies and unpub­lished observations have reported a significant benefit of the use of whole blood over red blood cells or acellular perfusates.2,3 This commentary explores the applicability, rather than the evidence-based significance, on the human level.

In general, the blood could be obtained from the donor, from matching donated blood, or from the recipient. Perhaps it could be possible to obtain blood for perfusion from the brain-dead donor before graft excision, while the donor is on support devices. This would allow the blood to contain the important supporting hormones and mediators that resist and/or improve the graft edema.4 However, in practice, this would be challenging as brain-dead donors are usually multiorgan donors, where the lungs are the last to be recovered, and the perfusion technique aims to maintain flow of 40% to 100% of the estimated cardiac output, depending on the applied protocol. In addition, the blood would also contain large amounts of inflammatory cytokines and death signals that could lead to deterioration of the graft instead of improvement. Although preclinical animal studies have reported a significant improvement with this method, the used blood was collected from “healthy” animal donors that were “killed” through collecting their blood (shock). In addition, post­transplant results with regard to this practice are scarce, thus not fully supporting or ruling out the questioned effects.

The next option could be the use of donated matching blood, which would mean exposing the marginal graft and its stimulated resident leukocytes to the plasma of another individual followed by the new host. A matter that may matter!

The last option could be the use of the recipient’s own blood. For this, there are 2 important concerns. First, whether the clinical status of the terminally ill patient would allow that. If yes, this could lead to the 2nd concern; exposing the marginal graft to the immune discrepancy of the new host before any reconditioning, which might not be a good idea. Therefore, although the use of the acellular perfusates has already achieved outstanding clinical results, the benefits of the whole blood perfusate should be further investigated. In addition, and if its application would be recommended, the above-mentioned technical alerts should be considered during the conduction of the clinical studies.

In 2014, an emerging EVLP protocol was described.1 This protocol advised the use of an acellular (supplemented) perfusate. However, with regard to the use of whole blood perfusion, the following considerations were advised: (1) the EVLP should run for at least 4 hours; (2) during the first 2 hours, donor blood together with a cytokine filter could be used; and (3) after graft conditioning has been established, the recipient’s blood could be used for the other 2 hours, to allow for a pretransplant graft/host degree of adaptation or at least controlled prediction of the interaction. Because the reported superiority of whole blood perfusion has been ascribed to multiple hormones in the plasma, especially during shock,4-8 supplementation of an acellular perfusate with those hormones may provide the same clinical benefits, without the exposure to any other possible hazard.9-11


References:

  1. Mohamed MS. Ex vivo lung perfusion and transplant: state of the art and view to the future. Exp Clin Transplant. 2015;13(6):493-499.
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  2. White CW, Hasanally D, Mundt P, et al. A whole blood-based perfusate provides superior preservation of myocardial function during ex vivo heart perfusion. J Heart Lung Transplant. 2015;34(1):113-121.
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  3. Loor G, Howard BT, Spratt JR, et al. Prolonged EVLP using OCS lung: cellular and acellular perfusates. Transplantation. 2017;101(10):2303-2311.
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  4. Woolf PD. Endocrinology of shock. Ann Emerg Med. 1986;15(12):1401-1405.
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  5. Lei J, Wendt CH, Fan D, Mariash CN, Ingbar DH. Developmental acquisition of T3-sensitive Na-K-ATPase stimulation by rat alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2007;292(1):L6-14.
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  6. Minakata Y, Suzuki S, Grygorczyk C, Dagenais A, Berthiaume Y. Impact of beta-adrenergic agonist on Na+ channel and Na+-K+-ATPase expression in alveolar type II cells. Am J Physiol. 1998;275(2):L414-422.
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  7. Matthay MA, Folkesson HG, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev. 2002;82(3):569-600.
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  8. Barquin N, Ciccolella DE, Ridge KM, Sznajder JI. Dexamethasone upregulates the Na-K-ATPase in rat alveolar epithelial cells. Am J Physiol. 1997;273(4):L825-830.
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  9. Mohamed MS. A cocktail solution for the ex vivo preservation and perfusion of the lung; Shehata solution. Transplant Open. 2016;1:1-13.
    CrossRef
  10. Mohamed MSA. Ex vivo lung perfusion; this idea deserves testing. Eur J Cardiothorac Surg. 2017;52(3):607.
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  11. Mohamed MS. Insulin supplementation of the lung graft cold preservation solution. Ann Thorac Surg. 2016;101(1):411-412.
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DOI : 10.6002/ect.2019.0272


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From MSAM for Medical Development, Bredstedt, Germany
Acknowledgements: The intellectual properties included in this manuscript belong solely to the author. Reproduction or use of any of these ideas requires the author’s written permission. No funding was provided for the development of this work. The author has no conflicts of interest to disclose..
Corresponding author: Mohamed S. A. Mohamed, MSAM for Medical Development, Theodor Storm Str. 1, 25821, Bredstedt, Germany
E-mail: mohammed.shehatta1@gmail.com