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. 2018 Mar 9;15(3):e1002522. doi: 10.1371/journal.pmed.1002522

Fig 3. Impairment of lung function secondary to trauma hemorrhage (TH) and resuscitation with stored blood and subsequent pneumonia is heme- and TLR4-dependent.

Fig 3

C57BL/6 or TLR4−/− mice underwent TH with fresh or stored red blood cell (RBC) resuscitation (with plasma 1:1) and subsequent P. aeruginosa K-strain (PAK)–induced pneumonia 48 h thereafter. Mice also received vehicle, hemopexin (HPX, 1 mg/kg in 100 μl of PBS) intravenously immediately before resuscitation, or TAK-242 (7.5 mg/kg) intravenously immediately before hemorrhage. (A) Survival after PAK administration. Each symbol represents an individual mouse. Data from fresh (0 storage days, circles, n = 12) or stored (14 storage days, squares, n = 9) RBCs are the same as presented in Fig 1A and collected and pooled over the entire project period as described in Methods. Triangles indicate stored RBCs + HPX (n = 5, *p < 0.001 relative to stored RBCs by log-rank test); inverted triangles indicate stored RBCs + TAK-242 (n = 5, *p < 0.001 relative to stored RBCs by log-rank test); open triangles indicate stored RBCs in TLR4−/− mice (n = 5, *p < 0.001 relative to stored RBCs by log-rank test); diamonds indicate fresh RBCs + HPX (n = 4, **p = 0.002 relative to fresh RBCs by log-rank test). (B) Mice underwent TH and resuscitation with either fresh (n = 6) or stored RBCs (n = 4), stored RBCs and hemopexin (n = 7), or stored RBCs and TAK-242 (n = 6). Forty-eight hours later, PAK was instilled, and 6 h thereafter mice were sacrificed and extravascular pulmonary equivalents (EVPE) measured. Data are mean ± SEM; each symbol represents an individual mouse. *p < 0.001 relative to fresh RBCs and #p < 0.001 relative to stored RBCs by 1-way ANOVA with Tukey post-test. (C) Mice underwent TH and resuscitation with either fresh (n = 5) or stored RBCs (n = 5), stored RBCs and hemopexin (n = 6), or stored RBCs and TAK-242 (n = 6). Forty-eight hours later, PAK was instilled, and 6 h thereafter mice were sacrificed and lung colony-forming units (CFU)/ml measured. Data are mean ± SEM; each symbol represents an individual mouse. *p < 0.001 relative to fresh RBCs and #p = 0.002 and ##p < 0.001 relative to stored RBCs by 1-way ANOVA with Tukey post-test. (D) Mice were administered PAK only by airway instillation (no TH or stored RBC resuscitation) (circles, n = 11), TAK-242 immediately prior to PAK instillation (squares, n = 3), or hemopexin immediately (triangles, n = 6) or 48 h (inverted triangles, n = 5) prior to PAK instillation, and survival monitored. *p = 0.022 for hemopexin administered immediately before PAK relative to PAK alone by log-rank test.