Protective effects of 10 °C preservation on donor lungs with lipopolysaccharide-induced acute lung injury

Abstract

Objectives: Hypothermic lung preservation at 10 °C has been recently shown to enhance quality of healthy donor lungs during ischemia. This study aims to show generalizability of the 10 °C lung preservation using an endotoxin-induced lung injury with specific focus on the benefits of post-transplant lung function and mitochondrial preservation.

Methods: Lipopolysaccharide (3 mg/kg) was injected intratracheally in rats to induce lung injury. Injured lungs were flushed with preservation solution and allocated to 3 groups (n = 6 each): minimum cold storage, 6-hour storage on ice (ice), and 6-hour storage at 10 °C (10 °C). Left lungs were transplanted and reperfused for 2 hours. After storage, lung tissue was used to evaluate the effects of hypothermic storage on the mitochondrial function: mitochondrial membrane potential was assessed by JC-1 staining; mitochondrial oxygen consumption was assessed using high-resolution respirometry.

Results: Two hours after reperfusion, the oxygen tension/inspired oxygen fraction ratio from the graft was significantly greater in the 10 °C group than in the Ice group (P = .015), whereas the wet-to-dry weight ratio was significantly lower (P = .041). Levels of interleukin-8 in lung tissues were significantly lower in the 10 °C group than in the Ice group (P = .004). Mechanistically, we noted greater mitochondrial membrane potential and elevated state III respiration in the 10 °C group than in the Ice group (P = .015 and P = .002, respectively), implying higher metabolic activities may be maintained during 10 °C preservation.

Conclusions: Favorable metabolism during 10 °C preservation prevented ischemia-induced mitochondrial damages in injured lungs, leading to better post-transplant outcomes.

Keywords: 10 °C preservation; acute lung injury; lipopolysaccharide; lung transplantation; mitochondrial health.