Revisiting an Old Concept in a New Era: 36 Hour Lung Preservation Using 10ºC Static Cold Storage

Abstract

Despite remote reports indicating 10°C to be the optimal temperature for cold static organ preservation (CSP), preservation of lungs in an ice cooler at 4°C remains the standard strategy in clinical transplantation. Here, we used a commercially available device that can keep a donor lung at 10°C conveniently and compared 10°C vs. 4°C during a prolonged period of CSP followed by functional and biological assessment of lung grafts. Lungs were procured from Yorkshire pigs (28-35kg), flushed with a low-potassium dextran solution and randomized into two groups (n=5 each): CSP at 4°C vs. CSP at 10°C (MyTemp Mini Incubator, Benchmark Scientific). After 36h of CSP, lungs were subjected to 12h of normothermic ex vivo lung perfusion (EVLP) with hourly functional assessment. Lung biopsies and perfusate samples were taken for biological and metabolic evaluation. During 12h of EVLP, lungs stored at 10°C presented superior physiological parameters compared to 4°C (Fig 1A). Reduced edema formation was seen as represented by a lower lung weight gain during EVLP (30 ± 34.1 vs. 201 ± 33.2 g, p = 0.0159). Metabolic profiles of the EVLP perfusate were significantly more favorable in the 10°C group compared to 4°C (Fig 1B). Furthermore, the 10°C group had significantly less inflammation demonstrated by lower levels of pro-inflammatory cytokines IL-1β (p = <0.0001, Fig 1C), and IL-8 (p = <0.0001, Fig 1C) in the EVLP perfusate. The levels of IL-6 were significantly lower in both EVLP perfusate (p = <0.0001, Fig 1C) and post-perfusion lung tissue (p = 0.0317). Immunohistochemical analysis for 8-Hydroxyguanosine demonstrated that lungs stored at 10°C tended to have less oxidative stress during CSP (p = 0.0952). With simple controllable refrigerators, 10°C preservation is easily achievable and provides significantly superior CSP in comparison to conventional 4°C storage. This could potentially remarkably improve the clinical and transportation logistics in lung transplantation.