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- Title
Static lung storage at 10°C maintains mitochondrial health and preserves donor organ function.
- Authors
Ali, Aadil; Wang, Aizhou; Ribeiro, Rafaela V. P.; Beroncal, Erika L.; Baciu, Cristina; Galasso, Marcos; Gomes, Bruno; Mariscal, Andrea; Hough, Olivia; Brambate, Edson; Abdelnour-Berchtold, Etienne; Michaelsen, Vinicius; Zhang, Yu; Gazzalle, Anajara; Fan, Eddy; Brochard, Laurent; Yeung, Jonathan; Waddell, Tom; Liu, Mingyao; Andreazza, Ana C.
- Abstract
Prolonging pulmonary preservation: Lungs can be preserved on ice for about 6 to 8 hours before transplantation, which imparts geographic and logistical restrictions on organ use. Ali et al. used pig lungs and ex vivo lung perfusion to show that increasing the static storage temperature from 4° to 10°C could maintain organ function while prolonging storage time. Increased storage temperature preserved mitochondrial function and led to greater abundance of mitochondrial metabolites. Human lungs stored at 10°C were successfully transplanted into five patients after storage times of about 10 to 16 hours, supporting the clinical utility of this approach. Cold static preservation on ice (~4°C) remains the clinical standard of donor organ preservation. However, mitochondrial injury develops during prolonged storage, which limits the extent of time that organs can maintain viability. We explored the feasibility of prolonged donor lung storage at 10°C using a large animal model and investigated mechanisms related to mitochondrial protection. Functional assessments performed during ex vivo lung perfusion demonstrated that porcine lungs stored for 36 hours at 10°C had lower airway pressures, higher lung compliances, and better oxygenation capabilities, indicative of better pulmonary physiology, as compared to lungs stored conventionally at 4°C. Mitochondrial protective metabolites including itaconate, glutamine, and N-acetylglutamine were present in greater intensities in lungs stored at 10°C than at 4°C. Analysis of mitochondrial injury markers further confirmed that 10°C storage resulted in greater protection of mitochondrial health. We applied this strategy clinically to prolong preservation of human donor lungs beyond the currently accepted clinical preservation limit of about 6 to 8 hours. Five patients received donor lung transplants after a median preservation time of 10.4 hours (9.92 to 14.8 hours) for the first implanted lung and 12.1 hours (10.9 to 16.5 hours) for the second. All have survived the first 30 days after transplantation. There was no grade 3 primary graft dysfunction at 72 hours after transplantation, and median post-transplant mechanical ventilation time was 1.73 days (0.24 to 6.71 days). Preservation at 10°C could become the standard of care for prolonged pulmonary preservation, providing benefits to both patients and health care teams.
- Publication
Science Translational Medicine, 2021, Vol 13, Issue 611, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abf7601