Transplantation/immunologyEvaluating lung injury at increasing time intervals in a murine brain death model

IntroductionOnly 15%-25% of brain death (BD) donors match the ideal donor criteria for lung transplantation. Lung injury may evolve in the hours after onset of brain death, but the evolution over time has not been well studied in lung. The aim of this study was to evaluate lung injury at different time points after BD using a murine model.Materials and methodsMale C57BL6/J mice (8-10 wk) were anesthetized, tracheotomized, and mechanically ventilated. Mice were randomly assigned to six groups (n = 8/group): 1 h, 3 h, and 6 h sham ([SH1], [SH3], [SH6]) and 1 h, 3 h, and 6 h brain death ([BD1], [BD3], [BD6]). BD was gradually induced by a subdural balloon catheter. Heart rate and mean arterial pressure were continuously monitored. At the end of the experiment, bronchoalveolar lavage was performed and the left lung was excised for histopathologic analysis.ResultsThe Cushing reflex was characterized by a rapid increase in heart rate and mean arterial pressure after balloon inflation in BD animals. An increase in percentage of neutrophils was seen with a longer follow-up period (P < 0.05). Interleukin 6 and interleukin 10 levels in bronchoalveolar lavage progressively increased with longer time intervals after BD ([BD1] versus [BD6]; P < 0.01). Histologic signs of lung injury (congestion, hemorrhage, and neutrophilic influx) were more pronounced in [BD3] and [BD6] compared with the other groups; however, this difference did not reach statistical significance.ConclusionThree hours after brain death, significant signs of inflammation and lung injury were seen compared with sham-operated animals. This murine BD model gives us opportunities for further mechanistic studies regarding treatment of BD-related donor lung injury.