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1

Citak, N., S. Arni, J. Cehn, L. Ceulemans, I. Schmitt-Opitz, and I. Inci. "Subnormothermic Ex Vivo Lung Perfusion Improves Graft Preservation in Rat Ex Vivo Lung Perfusion Model." Journal of Heart and Lung Transplantation 39, no. 4 (April 2020): S354. http://dx.doi.org/10.1016/j.healun.2020.01.416.

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2

Abdalla, Luis Gustavo, Karina Andrighetti de Oliveira Braga, Natalia Aparecida Nepomuceno, Lucas Matos Fernandes, Marcos Naoyuki Samano, and Paulo Manuel Pêgo-Fernandes. "Ex vivo lung perfusion in Brazil." Jornal Brasileiro de Pneumologia 42, no. 2 (April 2016): 95–98. http://dx.doi.org/10.1590/s1806-37562015000000099.

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Objective: To evaluate the use of ex vivo lung perfusion (EVLP) clinically to prepare donor lungs for transplantation. Methods: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated. Once every hour during the procedure, samples of the perfusate were collected and the function of the lungs was evaluated. Results: The mean PaO2 of the recovered lungs was 262.9 ± 119.7 mmHg at baseline, compared with 357.0 ± 108.5 mmHg after 3 h of EVLP. The mean oxygenation capacity of the lungs improved slightly over the first 3 h of EVLP-246.1 ± 35.1, 257.9 ± 48.9, and 288.8 ± 120.5 mmHg after 1, 2, and 3 h, respectively-without significant differences among the time points (p = 0.508). The mean static compliance was 63.0 ± 18.7 mmHg, 75.6 ± 25.4 mmHg, and 70.4 ± 28.0 mmHg after 1, 2, and 3 h, respectively, with a significant improvement from hour 1 to hour 2 (p = 0.029) but not from hour 2 to hour 3 (p = 0.059). Pulmonary vascular resistance remained stable during EVLP, with no differences among time points (p = 0.284). Conclusions: Although the lungs evaluated remained under physiological conditions, the EVLP protocol did not effectively improve lung function, thus precluding transplantation.
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3

Scharffenberg, Martin, Anne Naumann, Thomas Bluth, Marcelo de Abreu, Jörg Kotzerke, and Anja Braune. "Comparison of 68Ga- and fluorescence-labeled microspheres for measurement of relative pulmonary perfusion in anesthetized pigs." Nuklearmedizin 57, no. 03 (June 2018): 100–107. http://dx.doi.org/10.3413/nukmed-0970-18-04.

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Summary Aim: We compared 68Gallium (68Ga)- and fluorescence-labeled microspheres for measurement of pulmonary perfusion distribution in anesthetized pigs without lung injury. Methods: In two mechanically ventilated pigs, the distribution of pulmonary perfusion was marked in vivo with 68Ga- and fluorescence-labeled microspheres in supine and prone position. After each injection, the distribution of 68Ga-labeled microspheres was measured in vivo with positron emission tomography/ computed tomography (PET/CT) in the position in which microspheres were injected and vice versa. The distribution of fluorescence-labeled microspheres was measured ex vivo. Perfusion distributions were compared between methods and postures within four lung regions and along the ventro-dorsal gradient. After each injection of 68Ga-labeled microspheres, changes in ventro-dorsal perfusion gradients induced by repositioning were compared for volume- and mass-normalized PET/CT measurements. Results: Regional and gradient analyses of in vivo and ex vivo measurements, respectively, consistently revealed higher pulmonary perfusion in dorsal than ventral regions in supine positioned animals. Both methods showed more pronounced perfusion gradients in supine compared to prone position. Changes in animal position were associated with alterations in the ventro-dorsal perfusion gradient when volume-, but not mass-normalization was conducted for PET/CT data. Conclusions: Ex vivo fluorescence- and in vivo 68Ga-labeled microspheres measurements revealed similar perfusion distributions. Mass-normalized perfusion measurements by 68Ga-labeled microspheres and PET/CT were not affected by positioning artifacts.
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Olbertz, Carolin, Nikolaus Pizanis, Hagen Bäumker, Simon Becker, Clemens Aigner, Ursula Rauen, Ingo Nolte, Markus Kamler, and Achim Koch. "Effects of immediate versus delayed ex-vivo lung perfusion in a porcine cardiac arrest donation model." International Journal of Artificial Organs 42, no. 7 (June 25, 2019): 362–69. http://dx.doi.org/10.1177/0391398819841618.

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Objective:Ex-vivo lung perfusion is a promising tool to evaluate and recondition marginal donor lungs usually after a cold static preservation. The concept of continuous organ perfusion is supposed to reduce ischemic damage; however, the optimal perfusion protocol has not been established yet. The aim of this study was to compare immediate ex-vivo lung perfusion (I-EVLP) to delayed ex-vivo lung perfusion (D-EVLP) after a certain cold static preservation period on lung function in a large animal model.Methods:In a porcine model, lungs were procured after circulatory death and 60 min of no-touch warm ischemia. Lungs were preserved with single-flush cold low potassium dextran solution and prepared either for I-EVLP (n = 8) or stored cold for 9 h with subsequent D-EVLP (n = 8). Functional outcomes and morphology were compared during 4 h of ex-vivo lung perfusion, using STEEN SolutionTMas perfusion solution.Results:Pulmonary functional data, perfusate activities of lactate dehydrogenase, alkaline phosphatase, and products of lipid peroxidation did not differ significantly. There was a trend toward lower wet–dry ratio (I-EVLP: 13.4 ± 2.9; D-EVLP: 9.1 ± 2.5) and higher ΔpO2in D-EVLP group (I-EVLP: 209 ± 51.6 mmHg; D-EVLP: 236.3 ± 47.3 mmHg).Conclusion:In this donation-after-circulatory-death model, 9 h of cold static preservation followed by ex-vivo lung perfusion results in comparable pulmonary function to I-EVLP as indicated by oxygenation capacities and wet–dry ratio. Our findings indicate that prolonged cold static preservation prior to ex-vivo lung perfusion is as safe and effective as I-EVLP in the procurement of donor lungs.
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5

Guest, Bruce, Luis Arroyo, Laurent Viel, Carolyn Kerr, and John Runciman. "EX VIVO EQUINE HEART AND LUNG PERFUSION SYSTEM." Biomedical Engineering: Applications, Basis and Communications 27, no. 05 (October 2015): 1550045. http://dx.doi.org/10.4015/s1016237215500453.

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An ex vivo heart lung perfusion system (EVHLPS) was designed and constructed in order to facilitate the study of hemodynamic and mechanical phenomena associated with the equine pulmonary vascular system. Fresh en bloc heart and lung preparations collected from adult horses were placed in an enclosed chamber in normal anatomic orientation and perfused with isotonic phosphate buffered saline (PBS) via a closed loop, pulsatile perfusion system. Pulmonary artery (PA) pressure, left atrial pressure and perfusate temperature were regulated. Lungs were ventilated by static lung inflation and dynamic positive pressure ventilation (PPV). Instrumentation was introduced into the pulmonary arterial system via an instrument chamber incorporated in the perfusate flow piping upstream from the cranial vena cava. Key physiologic parameters (mean [SD]); PA flow (1.57 [0.61] L/min); systolic pressure (SAP) (42.5 [6.83] mmHg); diastolic pressure (DAP) (30.3 [3.86] mmHg); and perfusate temperature (37.1 [0.46]°C) were observed with en bloc heart and lung preparations (n = 5). PA pulse wave velocity (PWV) was found to vary from 1.72 to 12.50 m/s (n = 2) and appeared to have directly proportional relationships with mean arterial pressure (MAP) and distance within the PA.
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6

Warnecke, Gregor. "Normotherme maschinelle Ex-vivo-Perfusion von Spenderlungen." Zeitschrift für Herz-,Thorax- und Gefäßchirurgie 35, no. 4 (July 16, 2021): 242–47. http://dx.doi.org/10.1007/s00398-021-00442-1.

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7

Denlinger, Chadrick E. "Commentary: Ex vivo perfusion with green tea." Journal of Thoracic and Cardiovascular Surgery 161, no. 1 (January 2021): e79. http://dx.doi.org/10.1016/j.jtcvs.2020.01.052.

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8

Garza, G., A. Wang, J. Yune, Y. Zhang, J. Montagne, G. Loesch Siebiger, K. Yamanashi, et al. "Membraneless Perfusion - A Novel Technique for Ex Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 43, no. 4 (April 2024): S79. http://dx.doi.org/10.1016/j.healun.2024.02.162.

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9

Nakajima, Daisuke, and Hiroshi Date. "Ex vivo lung perfusion in lung transplantation." General Thoracic and Cardiovascular Surgery 69, no. 4 (March 8, 2021): 625–30. http://dx.doi.org/10.1007/s11748-021-01609-1.

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10

De Wolf, Julien, Philippe Puyo, Pierre Bonnette, Antoine Roux, Morgan Le Guen, François Parquin, Alain Chapelier, and Edouard Sage. "Logistic ex Vivo Lung Perfusion for Hyperimmunized Patients." Annals of Thoracic Surgery 102, no. 3 (September 2016): e205-e206. http://dx.doi.org/10.1016/j.athoracsur.2016.01.081.

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11

Cypel, Marcelo, Jonathan C. Yeung, Shin Hirayama, Matthew Rubacha, Stefan Fischer, Masaki Anraku, Masaaki Sato, et al. "Technique for Prolonged Normothermic Ex Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 27, no. 12 (December 2008): 1319–25. http://dx.doi.org/10.1016/j.healun.2008.09.003.

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12

Esipova, O. Yu, A. P. Kuleshov, V. K. Bogdanov, A. S. Esipov, E. A. Volkova, and N. V. Grudinin. "Development of a low priming volume hydrodynamic test bench for isolated ex vivo perfusion of small animal lungs." Russian Journal of Transplantology and Artificial Organs 26, no. 3 (July 3, 2024): 176–82. http://dx.doi.org/10.15825/1995-1191-2024-3-176-182.

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Objective: to develop and validate a hydrodynamic test bench (HTB) with a small filling volume for ex vivo normothermic machine perfusion (NMP) of donor lungs of small experimental animals (rats) using the open- loop technique.Materials and methods. An HTB was developed for ex vivo NMP of donor lungs of rats. It is a prefabricated structure with stands that hold the following equipment: a ventilator for small laboratory animals, a heating element, a low priming volume membrane oxygenator and a dome for donor lung storage, as well as roller peristaltic pump, sensors and device for invasive pressure measurement in the circuit, bubble filter and a line kit. Wistar rats (n = 6) were used to investigate the effectiveness of the HTB. Following the removal of donor lungs, the graft was positioned on the HTB and ex vivo lung perfusion (EVLP) was initiated with selected parameters. During the rat donor lung perfusion procedure, ex vivo PaO2/FiO2 ratio, oxygenation index (OI), pulmonary artery pressure (PAP) and peripheral pulmonary vascular resistance (pPVR) were measured.Results. High OI values were obtained at the end of the procedure (460 ± 32 at p = 0.028); constant PAP values were recorded in all cases throughout the EVLP procedure – from 9.13 to 7.93 mmHg at p > 0.05. The criterion for HTB functionality was pPVR, which tended to decrease in all cases – from 603.3 ± 56 to 89.1 ± 15 dynes/sec/cm–5 at p = 0.000. No design flaws impacting the donor lungs’ functional condition during ex vivo NMP procedure were found in the circuit of the hydrodynamic low priming volume bench during experimental studies.Conclusion. The efficiency and technical functionality of the HTB were demonstrated by the results of the experimental study conducted on the laboratory animals, rats. The observed dynamics of decrease in pPVR and the high OI values at stable PAP allowed for the conclusion that both the ex vivo perfusion itself and the technical design of the HTB are efficient.
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13

Ohsumi, Akihiro, Takashi Kanou, Aadil Ali, Zehong Guan, David M. Hwang, Thomas K. Waddell, Stephen Juvet, Mingyao Liu, Shaf Keshavjee, and Marcelo Cypel. "A method for translational rat ex vivo lung perfusion experimentation." American Journal of Physiology-Lung Cellular and Molecular Physiology 319, no. 1 (July 1, 2020): L61—L70. http://dx.doi.org/10.1152/ajplung.00256.2019.

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The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen ([Formula: see text]/[Formula: see text]) were observed during EVLP; however, lung compliance decreased over time in the 18-h group ( P = 0.012) and the [Formula: see text]/[Formula: see text] of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group ( P = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT.
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14

Haam, Seokjin. "Ex Vivo Lung Perfusion in Lung Transplantatio." Journal of Chest Surgery 55, no. 4 (August 5, 2022): 288–92. http://dx.doi.org/10.5090/jcs.22.056.

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15

Harrison, M. Shea, C. Corbin Frye, and Varun Puri. "Commentary: Outcomes and transferability of ex vivo lung perfusion." Journal of Thoracic and Cardiovascular Surgery 159, no. 1 (January 2020): 356–57. http://dx.doi.org/10.1016/j.jtcvs.2019.07.125.

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16

Aigner, C., A. Slama, K. Hötzenecker, B. Urbanek, W. Schmid, A. Scheed, G. Lang, S. Keshavjee, and W. Klepetko. "88 Clinical Ex Vivo Lung Perfusion – Pushing the Limits." Journal of Heart and Lung Transplantation 30, no. 4 (April 2011): S38. http://dx.doi.org/10.1016/j.healun.2011.01.095.

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17

Burki, S., K. Noda, B. Philips, P. G. Sanchez, A. Kumar, and J. D'Cunha. "Triptolide Attenuates Graft Inflammation During Ex Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 38, no. 4 (April 2019): S15. http://dx.doi.org/10.1016/j.healun.2019.01.020.

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18

Okamoto, T., I. Sakanoue, K. S. Ayyat, H. Niikawa, U. Ahmad, J. J. Yun, A. Bribriesco, et al. "Single Center Experience of Clinical Ex Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 39, no. 4 (April 2020): S373. http://dx.doi.org/10.1016/j.healun.2020.01.468.

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19

Dougherty, F. Carroll, F. M. Donovan,, and Mary I. Townsley. "Harmonic Analysis of Perfusion Pumps." Journal of Biomechanical Engineering 125, no. 6 (December 1, 2003): 814–22. http://dx.doi.org/10.1115/1.1632524.

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The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics. In addition, our data show that the key harmonic signatures are intrinsic to the perfusion pumps, are similar for flow and pressure waveforms, and are unchanged by characteristics of the downstream perfusion circuit or perfusate viscosity.
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20

Pan, Xufeng, Jun Yang, Shijie Fu, and Heng Zhao. "Application of ex vivo lung perfusion (EVLP) in lung transplantation." Journal of Thoracic Disease 10, no. 7 (July 2018): 4637–42. http://dx.doi.org/10.21037/jtd.2018.07.95.

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21

Brown, Chase R., Nicolas A. Brozzi, Nakul Vakil, Alexis E. Shafii, Sudish C. Murthy, Gosta B. Pettersson, and David P. Mason. "Donor Lungs With Pulmonary Embolism Evaluated with Ex Vivo Lung Perfusion." ASAIO Journal 58, no. 4 (2012): 432–34. http://dx.doi.org/10.1097/mat.0b013e318251cde4.

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22

Ayyat, K. S., T. Okamoto, A. Tantawi, I. Sakanoue, H. Elgharably, U. Ahmad, S. Unai, J. Yun, M. Budev, and K. McCurry. "Screening for Donor Lung Pulmonary Emboli During Ex-Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 42, no. 4 (April 2023): S39. http://dx.doi.org/10.1016/j.healun.2023.02.083.

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23

Ermert, L., H. R. Duncker, S. Rosseau, H. Schutte, and W. Seeger. "Morphometric analysis of pulmonary intracapillary leukocyte pools in ex vivo-perfused rabbit lungs." American Journal of Physiology-Lung Cellular and Molecular Physiology 267, no. 1 (July 1, 1994): L64—L70. http://dx.doi.org/10.1152/ajplung.1994.267.1.l64.

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Characterization and quantification of lung intracapillary leukocytes is of interest for a better understanding of immunological and inflammatory features in this organ. We developed a technique of computer-assisted measurement of digitalized electron-microscopic images and electronic data processing for morphometry of intracapillary leukocyte pools in rabbit lungs (L. Ermert, W. Seeger, and H.-R. Duncker, Cell Tissue Res. 271: 469-476, 1993). Measurements were undertaken in buffer-perfused isolated lungs (avoiding any reentry of washed-out cells); perfusion fixation was performed 7.5, 35, and 185 min after onset of artificial circulation (n = 5 each). Data were compared with that of nonperfused lungs fixed by tracheal instillation (baseline). Total lung capillary neutrophil counts were 1.41 x 10(9), 1.35 x 10(9), 1.37 x 10(9), and 0.69 x 10(9) (baseline, 7.5, 35, and 185 min perfusion, respectively). Corresponding data for intracapillary lymphocytes were 1.07 x 10(9), 0.84 x 10(9), 0.81 x 10(9), and 0.57 x 10(9); and for microvascular monocytes, data were 0.21 x 10(9), 0.19 x 10(9), 0.18 x 10(9), and 0.08 x 10(9). Ratios of cell volume and surface variables of the different intracapillary leukocyte types did not change during ex vivo lung perfusion. We conclude that the rabbit pulmonary capillary bed harbors large pools of different leukocytes, which surpass pool sizes of corresponding circulating cells and display very slow washout kinetics under conditions of lung-buffer perfusion. A major impact of these intracapillary leukocyte pools on immunological and inflammatory events in isolated-perfused and transplanted lungs must be assumed.
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24

Yeginsu, Ali. "Ex vivo lung perfusion in lung transplantation: a case report." Turkish Journal of Thoracic and Cardiovascular Surgery 24, no. 1 (January 4, 2016): 144–47. http://dx.doi.org/10.5606/tgkdc.dergisi.2016.11111.

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25

Schibilsky, D., M. Siepe, and F. Beyersdorf. "Ergebnisse der Transplantation von Spenderherzen nach normothermer Ex-vivo-Perfusion." Zeitschrift für Herz-,Thorax- und Gefäßchirurgie 33, no. 3 (August 7, 2018): 199–203. http://dx.doi.org/10.1007/s00398-018-0264-4.

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26

Van De Wauwer, C., Z. L. Zhang, E. A. Verschuuren, C. T. Gan, W. van der Bij, and M. E. Erasmus. "Is Logistically Motivated Ex Vivo Lung Perfusion a Good Idea?" Journal of Heart and Lung Transplantation 40, no. 4 (April 2021): S307. http://dx.doi.org/10.1016/j.healun.2021.01.871.

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27

Cypel, M., C. Aigner, E. Sage, T. Machuca, A. Slama, M. Stern, W. Klepetko, A. Chapelier, and S. Keshavjee. "Three Center Experience with Clinical Normothermic Ex Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 32, no. 4 (April 2013): S16. http://dx.doi.org/10.1016/j.healun.2013.01.021.

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28

Krishnan, A., M. Fawad, S. Elde, A. Garrison, J. Simmons, G. N. Cywinska, J. P. McNulty, et al. "Preservation of Bronchial Artery Circulation on Ex-Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 43, no. 4 (April 2024): S274. http://dx.doi.org/10.1016/j.healun.2024.02.1201.

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29

Williams, J. E., S. Schaefer, A. M. Williams, D. D. Odell, and K. H. Lagisetty. "Ex-Vivo Lung Perfusion: National Trends and Post-Transplant Outcomes." Journal of Heart and Lung Transplantation 43, no. 4 (April 2024): S416. http://dx.doi.org/10.1016/j.healun.2024.02.1324.

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30

Lynn, M., L. Radel, M. Iqbal, N. Baez Hernandez, M. Bano, R. Davies, and R. Butts. "Ex Vivo Normothermic Perfusion Use for Pediatric Heart Transplant Recipients." Journal of Heart and Lung Transplantation 43, no. 4 (April 2024): S633—S634. http://dx.doi.org/10.1016/j.healun.2024.02.996.

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31

Burki, S., K. Noda, A. Kumar, B. Philips, P. G. Sanchez, and J. D'Cunha. "Influence of Various Perfusion Temperatures on Lung Graft Preservation during Ex Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 38, no. 4 (April 2019): S240—S241. http://dx.doi.org/10.1016/j.healun.2019.01.593.

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32

Pashkov, I. V., S. V. Gautier, V. K. Bogdanov, D. O. Oleshkevich, D. M. Bondarenko, N. P. Mozheiko, N. S. Bunenkov, and N. V. Grudinin. "Normothermic <i>ex vivo</i> lung perfusion using a developed solution followed by orthotopic left lung transplantation (experimental study)." Russian Journal of Transplantology and Artificial Organs 25, no. 2 (July 16, 2023): 158–66. http://dx.doi.org/10.15825/1995-1191-2023-2-158-166.

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The continued unavailability of adequate organs for transplantation to meet the existing demand has resulted in a major challenge in transplantology. This is especially felt in lung transplantation (LTx). LTx is the only effective method of treatment for patients with end-stage lung diseases. Normothermic ex vivo lung perfusion (EVLP) has been proposed to increase the number of donor organs suitable for transplant – EVLP has proven itself in a number of clinical trials. The ability to restore suboptimal donor lungs, previously considered unsuitable for transplantation, can improve organ functionality, and thus increase the number of lung transplants. However, widespread implementation of ex vivo perfusion is associated with high financial costs for consumables and perfusate.Objective: to test the developed solution on an ex vivo lung perfusion model, followed by orthotopic LT under experimental conditions.Materials and methods. The experiment included lung explantation stages, static hypothermic storage, EVLP and orthotopic left LTx. Perfusion was performed in a closed perfusion system. We used our own made human albumin-based perfusion solution as perfusate. Perfusion lasted for 2 hours, and evaluation was carried out every 30 minutes. In all cases, static hypothermic storage after perfusion lasted for 4 hours. The orthotopic single-lung transplantation procedure was performed using assisted circulation, supplemented by membrane oxygenation. Postoperative follow-up was 2 hours, after which the experimental animal was euthanized.Results. Respiratory index before lung explantation was 310 ± 40 mmHg. The PaO2/FiO2 ratio had positive growth dynamics throughout the entire EVLP procedure. Oxygenation index was 437 ± 25 mm Hg after 120 minutes of perfusion. Throughout the entire EVLP procedure, there was a steady decrease in pulmonary vascular resistance (PVR). Initial PVR was 300 ± 100 dyn×s/cm5; throughout the EVLP, PVR tended to fall, reaching 38,5 ± 12 dyn×s/cm5 at the end of perfusion.Conclusion. A safe and effective EVLP using our perfusate is possible. The developed orthotopic left lung transplantation protocol under circulatory support conditions, supplemented by membrane oxygenation, showed it is efficient and reliable.
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33

Koerner, Michael M., Ali Ghodsizad, Uwe Schulz, Aly El Banayosy, Reiner Koerfer, and Gero Tenderich. "Normothermic Ex Vivo Allograft Blood Perfusion in Clinical Heart Transplantation." Heart Surgery Forum 17, no. 3 (July 3, 2014): 141. http://dx.doi.org/10.1532/hsf98.2014332.

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<p><b>Background:</b> Cold ischemia associated with cold static storage is an independent risk factor for primary allograft failure and survival of patients after orthotopic heart transplantation. The effects of normothermic ex vivo allograft blood perfusion on outcomes after orthotopic heart transplantation compared to cold static storage have been studied.</p><p><b>Methods:</b> In this prospective, nonrandomized, single-institutional clinical study, normothermic ex vivo allograft blood perfusion has been performed using an organ care system (OCS) (TransMedics, Andover, MA, USA). Included were consecutive adult transplantation patients who received an orthotopic heart transplantation (oHTx) without a history of any organ transplantation, in the absence of a congenital heart disorder as an underlying disease and not being in need of a combined heart-lung transplantation. Furthermore, patients with fixed pulmonary hypertension, ventilator dependency, chronic renal failure, or panel reactive antibodies >20% and positive T-cell cross-matching were excluded. Inclusion criteria for donor hearts was age of <55 years, systolic blood pressure >85 mmHg at the time of final heart assessment under moderate inotropic support, heart rate of <120 bpm at the time of explantation, and left ventricular ejection fraction >40% assessed by an transcutaneous echo/Doppler study with the absence of gross wall motion abnormalities, absence of left ventricular hypertrophy, and absence of valve abnormalities. Donor hearts which were conventionally cold stored with histidine-tryptophan-ketoglutarate solution (Custodiol; Koehler Chemie, Ansbach, Germany) constituted the control group. The primary end point was the recipients' survival at 30 days and 1 and 2 years after their heart transplantation. Secondary end points were primary and chronic allograft failure, noncardiac complications, and length of hospital stay.</p><p><b>Results:</b> Over a 2-year period (January 2006 to July 2008), 159 adult cardiac allografts were transplanted. Twenty-nine were assigned for normothermic ex vivo allograft blood perfusion and 130 for cold static storage with HTK solution. Cumulative survival rates at 30 days and 1 and 2 years were 96%, 89%, and 89%, respectively, whereas in the cold static storage group survival after oHTx was 95%, 81%, and 79%. Primary graft failure was less frequent in the recipients of an oHTx who received a donor heart which had been preserved with normothermic ex vivo allograft blood perfusion using an OCS (6.89% versus 15.3%; <i>P</i> = .20). Episodes of severe acute rejection (23% versus 17.2%; <i>P</i> = .73), as well as, cases of acute renal failure requiring haemodialysis (25.3% versus 10%; <i>P</i> = .05) were more frequent diagnosed among recipients of a donor heart which had been preserved using the cold static storage. The length of hospital stay did not differ (26 days versus 28 days; <i>P</i> = .80) in both groups.</p><p><b>Conclusions:</b> Normothermic ex vivo allograft blood perfusion in adult clinical orthotopic heart transplantation contributes to better outcomes after transplantation in regard to recipient survival, incidence of primary graft dysfunction, and incidence of acute rejection.</p>
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34

Pongratz, Christina, Jens Ziegle, Axel Boese, Michael Friebe, Helena Linge, and Thorsten Walles. "Temperature Controlled and Monitored Ex Vivo Lung Perfusion System for Research and Training Purposes." Current Directions in Biomedical Engineering 5, no. 1 (September 1, 2019): 293–95. http://dx.doi.org/10.1515/cdbme-2019-0074.

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AbstractEx vivo lung perfusion (EVLP) is a preservation method for donor lungs, which keep lungs viable in a physiological environment outside of a body for a short period of time. EVLP is established clinically for lung transplantation. Experimental applications for EVLP are e.g. lung cancer research or medical device development and testing. For preservation, a lung is ventilated artificially in an organ chamber and perfused antegrade through the pulmonary artery. Here we introduce a thermoregulation system for an experimental EVLP system to be used for translational research approaches as well as for training medical staff. To implement physiological culture conditions that are a prerequisite for lung preservation and tissue homeostasis, a thermoregulation is needed to rewarm the explanted lung tissue (storage temperature 4°C). Technically, the EVLP system must be thermally insulated, so loss of caloric is avoided. For monitoring, temperature sensors are integrated within the lung, in the organ chamber and in the afferent perfusate tube, whereby the measured values determine the thermoregulation. Initial tests using thermal packs (cooled to 4-6°C) placed on a heating mat, as a part of the perfusion circuit, showed that the perfusate temperature falls to 34°C, but restores after approximately 60 minutes (36.5°C), whereby the thermal pack is warmed. With this setup longer perfusion times should be obtained rather than without thermoregulation due to normothermic perfusion of the lung.
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Vallabhajosyula, Prashanth, Laxminarayana Korutla, Andreas Habertheuer, Sanjana Reddy, Christian Schaufler, Jared Lasky, Joshua Diamond, and Edward Cantu. "Ex Vivo Lung Perfusion Model to Study Pulmonary Tissue Extracellular Microvesicle Profiles." Annals of Thoracic Surgery 103, no. 6 (June 2017): 1758–66. http://dx.doi.org/10.1016/j.athoracsur.2016.11.074.

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Sato, K., L. See Hoe, N. Obonyo, K. Wildi, S. Colombo, M. Bouquet, M. Passmore, et al. "121 Hypothermic Ex Vivo Perfusion Preserves Post-Transplant Donor Cardiac Function." Heart, Lung and Circulation 29 (2020): S90. http://dx.doi.org/10.1016/j.hlc.2020.09.128.

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37

Urban, M., J. Boudreaux, H. M. Strah, B. Small, D. Berkheim, M. Moulton, F. Wilson, and A. Siddique. "Impact of Mobile Ex Vivo Lung Perfusion on Lung Transplant Finances." Journal of Heart and Lung Transplantation 40, no. 4 (April 2021): S309—S310. http://dx.doi.org/10.1016/j.healun.2021.01.876.

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38

Koch, A., N. Pizanis, G. Ayoub, A. Slama, A. Weymann, V. Bessa, C. Taube, C. Aigner, A. Ruhparwar, and M. Kamler. "Use of Ex Vivo Lung Perfusion for Lung Transplantation: Midterm Results." Journal of Heart and Lung Transplantation 40, no. 4 (April 2021): S310. http://dx.doi.org/10.1016/j.healun.2021.01.877.

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39

Wallinder, A., S. E. Ricksten, G. C. Riise, M. Silverborn, H. Liden, and G. Dellgren. "Transplantation of Initially Rejected Donor Lungs after Ex-Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 32, no. 4 (April 2013): S153. http://dx.doi.org/10.1016/j.healun.2013.01.353.

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40

Hopkins, P. M., D. C. Chambers, R. Naidoo, D. A. Wall, I. J. Smith, and W. G. Hunt. "Australia’s Experience with Ex-Vivo Lung Perfusion of Highly Marginal Donors." Journal of Heart and Lung Transplantation 32, no. 4 (April 2013): S154. http://dx.doi.org/10.1016/j.healun.2013.01.355.

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41

Deng, M., E. Soltesz, E. Hsich, Y. Naka, D. Mancini, F. Esmailian, J. Kobashigawa, et al. "Ex-Vivo Perfusion of Human Donor Hearts Reduces Cold Ischemia Time." Journal of Heart and Lung Transplantation 32, no. 4 (April 2013): S156. http://dx.doi.org/10.1016/j.healun.2013.01.362.

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42

Ayyat, K. S., T. Okamoto, H. Niikawa, H. Elgharably, Y. Itoda, R. Fairchild, and K. R. McCurry. "Reperfusion Inflammatory State of Human Lungs during Cellular Ex-Vivo Perfusion." Journal of Heart and Lung Transplantation 38, no. 4 (April 2019): S241. http://dx.doi.org/10.1016/j.healun.2019.01.594.

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43

Miller, D., N. Wrenn, M. Tran, J. Murala, K. Gaskie, A. Banga, F. Torres, and M. Wait. "Establishing a Nursing-Led Ex-Vivo Lung Perfusion Program: A Primer." Journal of Heart and Lung Transplantation 38, no. 4 (April 2019): S301—S302. http://dx.doi.org/10.1016/j.healun.2019.01.757.

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44

Halpern, A. L., S. A. Hirji, L. J. Helmkamp, S. Roberts, A. K. Houk, A. K. Okoh, R. A. Meguid, D. E. Rinewalt, and M. J. Weyant. "Ex Vivo Lung Perfusion for Circulatory Death Donors in Lung Transplantation." Journal of Heart and Lung Transplantation 39, no. 4 (April 2020): S110—S111. http://dx.doi.org/10.1016/j.healun.2020.01.978.

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45

Balasubramanian, P., M. Thomas, I. Makey, F. Alvarez, T. Narula, S. Pham, K. Landolfo, et al. "Remote vs Local Ex-Vivo Lung Perfusion, a Single Center Experience." Journal of Heart and Lung Transplantation 42, no. 4 (April 2023): S525—S526. http://dx.doi.org/10.1016/j.healun.2023.02.1441.

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46

Arni, Stephan, Tatsuo Maeyashiki, Necati Citak, Isabelle Opitz, and Ilhan Inci. "Subnormothermic Ex Vivo Lung Perfusion Temperature Improves Graft Preservation in Lung Transplantation." Cells 10, no. 4 (March 29, 2021): 748. http://dx.doi.org/10.3390/cells10040748.

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Normothermic machine perfusion is clinically used to assess the quality of marginal donor lungs. Although subnormothermic temperatures have proven beneficial for other solid organ transplants, subnormothermia-related benefits of ex vivo lung perfusion (EVLP) still need to be investigated. Material and Methods: In a rat model, we evaluated the effects of 28 °C temperature on 4-h EVLPs with subsequent left lung transplantation. The recipients were observed for 2 h postoperatively. Lung physiology data were recorded and metabolic parameters were assessed. Results: During the 4-h subnormothermic EVLP, the lung oxygenation was significantly higher (p < 0.001), pulmonary vascular resistance (PVR) lower and dynamic compliance (Cdyn) higher when compared to the 37 °C EVLP. During an end-of-EVLP stress test, we recorded significantly higher flow (p < 0.05), lower PVR (p < 0.05) and higher Cdyn (p < 0.01) in the 28 °C group when compared to the 37 °C group. After the left lung transplantation, Cdyn and oxygenation improved in the 28 °C group, which were comparable to the 37 °C group. Chemokines RANTES, MIP-3α, MIP-1α MCP-1 GRO/KC and pro-inflammatory mediators GM-CSF, G-CSF and TNFα were significantly lower after the 28 °C EVLP and remained low in the plasma of the recipient rats after transplantation. The lungs of the 28 °C group showed significantly lowered myeloperoxidase activity and lowered levels of TNFα and IL-1β. Conclusions: Compared to the normothermic perfusion, the 28 °C EVLP improved Cdyn and PVR and reduced both the release of pro-inflammatory cytokines and myeloperoxidase activity in lung tissue. These observations were also observed after the left lung transplantation in the subnormothermic group. The 28 °C EVLP significantly improved biochemical, physiological and inflammatory parameters in lung donors.
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Wong, Aaron, Ricardo Zamel, Jonathan Yeung, Gary D. Bader, Claudia C. Dos Santos, Xiaohui Bai, Yubo Wang, Shaf Keshavjee, and Mingyao Liu. "Potential therapeutic targets for lung repair during human ex vivo lung perfusion." European Respiratory Journal 55, no. 4 (February 14, 2020): 1902222. http://dx.doi.org/10.1183/13993003.02222-2019.

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IntroductionThe ex vivo lung perfusion (EVLP) technique has been developed to assess the function of marginal donor lungs and has significantly increased donor lung utilisation. EVLP has also been explored as a platform for donor lung repair through injury-specific treatments such as antibiotics or fibrinolytics. We hypothesised that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation.Materials and methodsRetrospective transcriptomics analyses were performed with peripheral tissue biopsies from “donation after brain death” lungs, with 46 pre-/post-transplant pairs and 49 pre-/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP.Results22 pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death and downregulation of metabolism. Eight pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. 27 pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism and protein synthesis. Of the inflammatory clusters, Toll-like receptor/innate immune signal transduction adaptor signalling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models.ConclusionEVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation.
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Nilsson, Tobias, Christoffer Hansson, Andreas Wallinder, Carl-Johan Malm, Martin Silverborn, Sven-Erik Ricksten, and Göran Dellgren. "Hemofiltration in ex vivo lung perfusion—a study in experimentally induced pulmonary edema." Journal of Thoracic and Cardiovascular Surgery 151, no. 2 (February 2016): 570–75. http://dx.doi.org/10.1016/j.jtcvs.2015.06.046.

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Yamada, T., D. Nakajima, J. Sakamoto, F. Chen, T. Okamoto, A. Ohsumi, T. Fujinaga, et al. "422 Reconditioning of Lungs with Pulmonary Edema in Ex Vivo Lung Perfusion Circuit." Journal of Heart and Lung Transplantation 30, no. 4 (April 2011): S144. http://dx.doi.org/10.1016/j.healun.2011.01.431.

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50

Iskender, I., T. Cosgun, S. Arni, M. Trinkwitz, S. Fehlings, N. Cesarovic, T. Frauenfelder, W. Weder, and I. Inci. "Cytokine Filtration Modulates Pulmonary Metabolism and Edema Formation During Ex Vivo Lung Perfusion." Journal of Heart and Lung Transplantation 35, no. 4 (April 2016): S142—S143. http://dx.doi.org/10.1016/j.healun.2016.01.393.

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