Protective effects of modified UW solution with dexmedetomidine and xenon on swine lung for donation after cardiac death

Abstract

Objective To explore the protective effects of dexmedetomidine (DEX) and xenon (Xe) modified university of Wisconsin solution (UW solution) in a pig model of lung donation after cardiac death (DCD). Methods Four healthy male mini-musk pigs aged 4-6 months, weighing 13-17 kg, were subjected to cardiac arrest by cis-atracurium infusion and cessation of oxygen supply. After 1 h of warm ischemia (WI), the lungs were harvested and cut into thin slices. Some of the slices served as WI group, while the other slices were preserved in N2/DEX/Xe added 4 types of UW solutions at 4 ℃ for 24 h of cold ischemia (CI). These slices were divided into WI+CI+N2 group, WI+CI+DEX group, WI+CI +DEX +30% Xe group, and WI+CI+DEX+50% Xe group. The above 5 group of tissue slices were stained with HE for pathological score. Apoptosis of pulmonary cells were detected by TUNEL. Western blotting was used to detect the expression of cleaved Caspase-3 and glutathione peroxidase 4 (GPX4). The expression of GPX4 and high mobility group protein 1 (HMGB1) were assessed by immunohistochemical staining. Results Compared with the WI group, the histology of other groups showed no significant damage to alveolar structures. Pulmonary edema and inflammatory cell infiltration were not obvious. The injury score of lung had no significant change in lung tissues of all groups (P>0.05). Compared with the WI group, the number of TUNEL-positive cells and the protein level of cleaved Caspase-3 were increased in the WI+CI+N2 group (P < 0.05). However, the protein level of GPX4 had no significant change in lung tissues of all groups. Compared with the WI group, the protein level of HMGB1 was elevated in the WI+CI+N2 group (P < 0.05). Compared with the WI+CI+N2 group, the number of TUNEL-positive cells was significantly reduced in the WI+CI+DEX group, WI+CI+DEX+30%Xe group and WI+CI+DEX+50%Xe group (P < 0.001, P < 0.05, P < 0.05, respectively). The protein level of HMGB1 was significantly reduced in the WI+CI+DEX+30%Xe group (P < 0.01). Conclusion The UW solution added with DEX alone or in combination with Xe can provide better cell protection on swine DCD lung through inhibiting cell apoptosis, down-regulating expression and restraining cytoplasmic translocation of HMGB1.

Keywords

• donation after cardiac death
• dexmedetomidine
• xenon