Subnormothermic ex vivo lung perfusion attenuates graft inflammation in a rat transplant model
| Autor: | Robert Patrick Davis, William Parker, Matthew G. Hartwig, Mingqing Song, Andrew S. Barbas, John Yerxa, Jared N. Gloria, Minghua Zhu, Mariya L. Samoylova, Samuel J. Kesseli, Min Zhang |
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| Rok vydání: | 2022 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Cold storage 030204 cardiovascular system & hematology Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Fraction of inspired oxygen medicine.artery medicine Animals Lung Inflammation business.industry Organ Preservation Oxygenation respiratory system Rats Oxygen Perfusion Transplantation medicine.anatomical_structure 030228 respiratory system Rats Inbred Lew Reperfusion Injury Pulmonary artery Surgery Cardiology and Cardiovascular Medicine business Ex vivo Lung Transplantation |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 164:e59-e70 |
| ISSN: | 0022-5223 |
| DOI: | 10.1016/j.jtcvs.2021.01.066 |
| Popis: | Objective Ex vivo lung perfusion has emerged as a novel technique to safely preserve lungs before transplantation. Recent studies have demonstrated an accumulation of inflammatory molecules in the perfusate during ex vivo lung perfusion. These proinflammatory molecules, including damage-associated molecular patterns and inflammatory cytokines, may contribute to acute and chronic allograft dysfunction. At present, ex vivo lung perfusion is performed clinically at normothermic temperature (37°C). The effect of lowering temperature to the subnormothermic range during ex vivo lung perfusion has not been reported. In this study, we hypothesized that lower ex vivo lung perfusion temperature will lead to a reduction in allograft inflammation and result in improved post-transplant graft function. Methods Lewis rat heart-lung blocs underwent 4 hours of ex vivo lung perfusion in 3 temperature groups: 37°C (MP37), 30°C (MP30), and 25°C (MP25). In the control group, lung grafts were preserved by static cold storage before transplantation. After ex vivo lung perfusion or static cold storage, the left lung was transplanted for 2 hours before the animal was killed. Sera and tissue were collected and analyzed. Results There were no differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios during 4 hours of ex vivo lung perfusion between temperature groups. Tumor necrosis factor α significantly increased in the MP37 group during ex vivo lung perfusion, whereas this was not seen at lower temperatures. Extracellular DNA and high-mobility group box 1 perfusate concentrations increased significantly during ex vivo lung perfusion in all groups, but the rate of increase was diminished at lower temperature. Two hours post-transplant, there were no significant differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios of the lung graft or serum damage-associated molecular pattern levels among groups. On histologic grading after transplantation, greater injury was observed in the MP30 and MP37 groups, but not MP25, when compared with static cold storage. Conclusions Subnormothermic ex vivo lung perfusion at 25°C reduces the production of inflammatory mediators during ex vivo lung perfusion and is associated with reduced histologic graft injury after transplantation. |
| Databáze: | OpenAIRE |
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