First Human Transplantation of a Nonacceptable Donor Lung After Reconditioning Ex Vivo

Steen, Stig; Ingemansson, Richard; Eriksson, Leif; Pierre, Leif; Algotsson, Lars; Wierup, Per; Liao, Qiuming; Eyjolfsson, Atli; Gustafsson, Ronny; Sjöberg, Trygve

doi:10.1016/j.athoracsur.2007.01.033

Cited by 224 publications

(163 citation statements)

References 8 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…Recent clinical studies have tested varying periods of normothermic perfusion ("reconditioning") of donor organs transported in a cold state for the kidney (11) and lung (12,13). However, these studies have not achieved normothermic preservation throughout the period from explantation to implantation.…”

Section: Introductionmentioning

confidence: 99%

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Ravikumar

Jassem

Mergental

et al. 2016

American Journal of Transplantation

396

401

View full text Add to dashboard Cite

Joint first authors. ISRCTN 14355416.The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group ) versus , p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.Abbreviations: AST, aspartate transaminase; DBD, donation after brain death; DCD, donation after circulatory death; IRI, ischemia-reperfusion injury; IVC, inferior vena cava; MELD, model for end-stage liver disease; NHSBT, National Health Service Blood and Transplant; NMP, normothermic machine perfusion

show abstract

Section: Introductionmentioning

confidence: 99%

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Ravikumar

Jassem

Mergental

et al. 2016

American Journal of Transplantation

396

401

View full text Add to dashboard Cite

show abstract

“…However, the advent of ex vivo lung perfusion (EVLP) provides a unique opportunity to study immune extravasation immediately following revascularization. EVLP allows evaluation and reconditioning of donor lungs that would otherwise be clinically rejected for transplantation (9,10). It utilizes a protective strategy of organ reperfusion that replicates the in vivo environment, providing a physiological representation of the events occurring immediately posttransplantation.…”

Section: Introductionmentioning

confidence: 99%

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion

Stone

Critchley

Major

et al. 2016

American Journal of Transplantation

View full text Add to dashboard Cite

Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLPreduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.

show abstract

“…(20) More recently, the introduction of ex vivo lung reconditioning (21) and donation after cardiocirculatory death (4) have reignited the controversy and underscored the need to re-evaluate the preservation solutions that are currently used.…”

Section: Resultsmentioning

confidence: 99%

“…(3) Despite the evidence, controversy remains regarding the benefits of the LPD solution in terms of late graft performance and one-year mortality after transplantation. (20) More recently, the introduction of ex vivo lung reconditioning (21) and donation after cardiocirculatory death (4) have reignited the controversy and underscored the need to re-evaluate the preservation solutions that are currently used.…”

mentioning

confidence: 99%

Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação histopatológica e de apoptose celular em pulmões preservados com solução de baixo potássio dextrana vs. solução histidina-triptofano-cetoglutarato

et al. 2012

View full text Add to dashboard Cite

Objective: To compare histopathological findings and the degree of apoptosis among rat lungs preserved with low-potassium dextran (LPD) solution, histidine-tryptophan-ketoglutarate (HTK) solution, or normal saline (NS) at two ischemia periods (6 h and 12 h) using an experimental rat model of ex vivo lung perfusion. Methods: Sixty Wistar rats were anesthetized, randomized, and submitted to antegrade perfusion via pulmonary artery with one of the preservation solutions. Following en bloc extraction, the heart-lung blocks were preserved for 6 h or 12 h at 4°C and then reperfused with homologous blood for 60 min in an ex vivo lung perfusion system. At the end of the reperfusion, fragments of the middle lobe were extracted and processed for histopathological examination. The parameters evaluated were congestion, alveolar edema, alveolar hemorrhage, inflammatory infiltrate, and interstitial infiltrate. The degree of apoptosis was assessed using the TdT-mediated dUTP nick end labeling method. Results: The histopathological examination showed that all of the lungs preserved with NS presented alveolar edema after 12 h of ischemia. There were no statistically significant differences among the groups in terms of the degree of apoptosis. Conclusions: In this study, the histopathological and apoptosis findings were similar with the use of either LPD or HTK solutions, whereas the occurrence of edema was significantly more common with the use of NS. Keywords: Organ preservation; Organ preservation solutions; Lung transplantation; Reperfusion injury; Apoptosis. ResumoObjetivo: Comparar os achados histopatológicos e de apoptose em pulmões de ratos preservados em soluções low-potassium dextran (LPD, baixo potássio dextrana), histidine-tryptophan-ketoglutarate (HTK, histidina-triptofano-cetoglutarato) ou salina normal (SN) em 6 h e 12 h de isquemia pela utilização de um modelo experimental de perfusão pulmonar ex vivo. Métodos: Sessenta ratos Wistar foram anestesiados, randomizados e submetidos à perfusão anterógrada pela artéria pulmonar com uma das soluções preservadoras. Após a extração, os blocos cardiopulmonares foram preservados por 6 ou 12 h a 4°C, sendo então reperfundidos com sangue homólogo em um sistema de perfusão ex vivo durante 60 min. Ao final da reperfusão, fragmentos do lobo médio foram extraídos e processados para histopatologia, sendo avaliados os seguintes parâmetros: congestão, edema alveolar, hemorragia alveolar, hemorragia, infiltrado inflamatório e infiltrado intersticial. O grau de apoptose foi avaliado pelo método TdT-mediated dUTP nick end labeling. Resultados: A histopatologia demonstrou que todos os pulmões preservados com SN apresentaram edema alveolar após 12 h de isquemia. Não houve diferenças em relação ao grau de apoptose nos grupos estudados. Conclusões: No presente estudo, os achados histopatológicos e de apoptose foram semelhantes com o uso das soluções LPD e HTK, enquanto a presença de edema foi significativamente maior com o uso de SN. Descritores: Preservação de órgãos; Soluções para...

show abstract

First Human Transplantation of a Nonacceptable Donor Lung After Reconditioning Ex Vivo

Abstract: Rejected donor lungs may be successfully transplanted after being reconditioned ex vivo.

Cited by 224 publications

References 8 publications

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion

Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação histopatológica e de apoptose celular em pulmões preservados com solução de baixo potássio dextrana vs. solução histidina-triptofano-cetoglutarato

Contact Info

Product

Resources

About