Evaluation of Ventilation at 10C as the Optimal Storage Condition for Donor Lungs in a Murine Model

Abstract

RationaleCold static preservation at 4{degrees}C is the clinical standard for donor lung storage but is limited to 6-8 hours of cold ischemia. Static storage at 10{degrees}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{degrees}C would further prolong preservation by stimulating aerobic metabolism. MethodsLungs were procured from C57Bl/6 mice and then stored for 24h with ventilation at 10{degrees}C (n=4), statically at 10{degrees}C (n=4), or statically at 4{degrees}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. ResultsDonor lungs stored with ventilation at 10{degrees}C exhibited significantly reduced histologic injury scores compared to static storage at 4{degrees}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{degrees}C and 10{degrees}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{degrees}C. ConclusionsVentilating lungs at 10{degrees}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.