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A post-preservation vascular flush removes significant populations of donor leukocytes prior to lung transplantation
Institution:1. Department of Laboratory Methods, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, CZ-14021 Prague, Czech Republic;2. Third Faculty of Medicine, Charles University, Ruská 87, 100 00 Praha 10, Czech Republic;3. Cardiology Clinic, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, CZ-14021 Prague, Czech Republic;1. Hackensack Meridian Health, Centre for Discovery & Innovation, Nutley, New Jersey;2. Department of Medicine, Hematology-Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
Abstract:BackgroundDonor leukocytes are intrinsically involved in acute lung allograft rejection, via self-presentation of donor antigens to recipient leukocytes. Therapeutic modalities to remove donor leukocytes are currently unavailable. We evaluated if a vascular flush immediately following preservation can be used for this purpose.MethodsA post-preservation flush was performed with STEEN solution in n = 6 porcine lungs following static cold storage. The first 500 ml effluent from the left atrium was collected and an inflammatory profile performed.ResultsA total of 1.17 billion (±2.8 × 108) viable leukocytes were identified within the effluent. T cells were the dominant cell population, representing 82% of the total mobilised leukocytes, of which <0.01% were regulatory T cells. IL-18 was the most abundant cytokine, with a mean concentration of 84,216 pg (±153,552 pg). In addition, there was a mean concentration of 8819 ng (±4415) cell-free mitochondrial DNA.ConclusionThere is an immediate transfer of donor leukocytes, cytokines and damage-associated molecular patterns following reperfusion. Such a pro-inflammatory donor load may enhance alloantigen presentation and drive recipient alloimmune responses. A post-preservation flush may therefore be an effective method for reducing the immune burden of the donor lung prior to transplantation.
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