Effects of Subnormothermic Ex Vivo Lung Perfusion on Inflammatory Injury in a Murine Lung Transplant Model
1Duke University School of Medicine, Durham, NC, 2Department of Surgery, Duke University Medical Center, Durham, NC, 3Department of Thoracic Surgery, Duke University Medical Center, Durham, NC
Meeting: 2020 American Transplant Congress
Abstract number: A-375
Keywords: Inflammation, Lung, Lung preservation, Lung transplantation
Session Name: Poster Session A: Ischemia Reperfusion & Organ Rehabilitation
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Ex vivo lung perfusion (EVLP) has emerged as a technique that safely preserve lungs prior to transplantation. Recent evidence demonstrates increased levels of inflammatory molecules in animal models during EVLP. These pro-inflammatory molecules, such as Damage Associated Molecular Patterns (DAMPs) and pro-inflammatory cytokines (TNFα) contribute to acute and chronic allograft dysfunction. At present, EVLP is conducted at normothermia. The effect of lowering temperature during EVLP has not yet been investigated. Thus, we hypothesize that a reduction in temperature will lead to a reduction in pro-inflammatory cytokines and DAMPs (exDNA) during EVLP.
*Methods: Lewis rat heart-lung blocs underwent 4 hours of EVLP in three groups: 37◦C (MP37), 30◦C (MP30), and 25◦C (MP25). STEEN SolutionTM, Cefazolin, Methylprednisolone, and Heparin were used to emulate perfusate utilized in commercially available devices. The control group was kept in static cold storage (SCS) prior to transplantation. During EVLP, ventilatory parameters and perfusate were collected hourly. Lung protective ventilation strategies were utilized (PEEP 2.5-3 cmH2O, VT 5mL/kg, RR 60). The target perfusate flow rate was 20% of the cardiac output. After EVLP or SCS, the left lung was transplanted for 2 hours before animal sacrifice. Sera and tissue were collected and analyzed for DAMPs and cytokines.
*Results: There were no significant differences in P/F (PaO2/FiO2) ratios during 4 hours of EVLP between temperature groups (mean±SEM). However, there was a trend of increased pulmonary artery (PA) pressure in the MP37 group (n=6) (7.59±1.33mmHg at 4h) compared to MP30 (n=7) (5.16±0.29mmHg at 4h) and MP25 (n=6) (5.24±0.46mmHg at 4h). TNFα significantly increased in the MP37 group during EVLP (0.008±0.008pg/mL at 1h, 145.80±45.50pg/mL at 4h p=0.024). There were no increases in TNFα levels in the MP30 or MP25 group. ExDNA increased significantly during EVLP (MP37 [737.43±85.06ng/mL/kg at 1h, 938.43±75.55ng/mL/kg at 4h, p=0.01]; MP30 [816.60±33.41ng/mL/kg at 1h, 970.70±58.61ng/mL/kg at 4h p=0.003]; MP25 [745±32.16ng/mL/kg at 1h, 843.30±33.91ng/mL/kg at 4h p=0.098]), but was not significantly different between temperature groups. 2 hours post-transplant, there were no significant differences in P/F ratios or exDNA levels among groups. TNFα was found to be significantly higher in the MP37 group (n=5) (250.3±135.4ng/mL/kg p=0.0496) compared to the SCS group (n=7) (0±0), but there were no significant differences in MP30 and MP25 compared to SCS.
*Conclusions: Subnormothermic EVLP temperatures can attenuate inflammatory mediators produced during EVLP. Lower EVLP temperature has a lower inflammatory profile which could lead to better outcomes post-transplant.
To cite this abstract in AMA style:Gloria JN, Kesseli SJ, Yerxa J, Zhang M, Zhu M, Parker W, Davis RP, Barbas AS, Hartwig MG. Effects of Subnormothermic Ex Vivo Lung Perfusion on Inflammatory Injury in a Murine Lung Transplant Model [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/effects-of-subnormothermic-ex-vivo-lung-perfusion-on-inflammatory-injury-in-a-murine-lung-transplant-model/. Accessed March 26, 2023.
« Back to 2020 American Transplant Congress