Abstract
Cold static preservation at 4 °C is the clinical standard for donor lung storage but is limited to 6–8 h of cold ischemia. Static storage at 10 °C has been shown to extend ischemia times and improve lung health. Given that lungs can maintain aerobic metabolism ex vivo, we hypothesized that adding ventilation at 10 °C would further prolong preservation by stimulating aerobic metabolism. Lungs were procured from C57Bl/6 mice and then stored for 24 h with ventilation at 10 °C (n = 4), statically at 10 °C (n = 4), or statically at 4 °C (n = 4). Respiratory mechanics were evaluated using a FlexiVent system. Cellular viability was assessed via flow cytometry. Complement shedding was evaluated by enzyme-linked immunosorbent assay. Histologic evidence of lung injury was assessed by H&E staining. Donor lungs stored with ventilation at 10 °C exhibited significantly reduced histologic injury scores compared to static storage at 4 °C (p = 0.0062). Ventilation also decreased complement C3 shedding (p < 0.01), apoptosis (p < 0.05), cytochrome c release (p = 0.0014), and ROS production (p = 0.0008) compared to statically stored lungs at 4 °C and 10 °C. Functionally, ventilated lungs demonstrated improved respiratory mechanics with lower airway resistance (p = 0.021) and increased compliance (p = 0.023) compared to static storage at 10 °C. Ventilating lungs at 10 °C compared to static cold storage appears to result in healthier and more functional lung tissue and may extend the preservation times of donor organs for lung transplantation.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors would like to thank Jessica Forcucci, M.D., and Ellen Riemer, M.D., for their expert assistance in the blinded histopathological grading of the H&E slides. We would also like to acknowledge Konrad Rajab, MD, for his contributions during the early stages of this project, including concept development and support in obtaining initial resources.
Funding
This work was funded by SCTR UL1-TR001450 and supported by the NIH Pulmonary Focused Foundations in Innovation and Scholarship (PUFFINS) T32 HL144470.
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MAH made substantial contributions to the conception and design of the work, acquisition and analysis of the data, interpretation of the data, and drafted and revised the work. MT made substantial contributions to the conception and design of the work, acquisition and analysis of the data, interpretation of the data, and drafted and revised the work. BW made substantial contributions to the acquisition and analysis of the data, interpretation of the data, and helped draft the work. RO made substantial contributions to the conception and design of the work, interpretation of the data, and revised the work. CA made substantial contributions to the conception and design of the work, interpretation of the data, revised the work. KE made substantial contributions to the conception and design of the work, interpretation of the data, and drafted and revised the work. BG made substantial contributions to the conception and design of the work, acquisition and analysis of the data, interpretation of the data, and drafted and revised the work. All authors have approved the submitted version and have agreed to both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.
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This study was approved by the Institutional Animal Care and Use Committee (IACUC) following the National Institutes of Health Guide for Care and Use of Laboratory Animals (IACUC Protocol ID 2022 − 01479).
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Hill, M.A., Tennant, M., Watts, B. et al. Evaluation of ventilation at 10 °C as the optimal storage condition for donor lungs in a murine model. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35943-2
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DOI: https://doi.org/10.1038/s41598-026-35943-2
