Figure 5. Zinc deficiency promotes VILI and correlates with lower metallothionein (MT) lung protein levels.

(A) Zinc-deficient mice (n = 15) exhibited significantly increased physiologic dysfunction (increased elastance) compared with control mice (n = 7). *P < 0.05 versus control by 2-way repeated measures ANOVA after mechanical ventilation with modest tidal volumes (15 ml/kg tidal volume for 8 hours, percentage change from baseline) as well as with injurious tidal volumes (24 ml/kg for 8 hours) with a significant increase in elastance (B). *P < 0.05 by 2-way ANOVA with Bonferroni post-hoc test, n = 6 mice/control and 7 mice/zinc-deficient group; data presented as mean + SEM. (C) Lungs were harvested from mice subjected to ventilator-induced lung injury (VILI) as in panel B (n = 3–4/group) and pooled, and then harvested for protein and analyzed by Western blotting for MT or loading control (β-actin). (D–F) After 8 hours of mechanical ventilation with modest tidal volumes (mechanical ventilation 15 ml/kg), bronchoalveolar lavage (BAL) fluid was collected and analyzed for (D) total cell counts (baseline n = 6–9/ group, VILI n = 7–15 per group for both diets); (E) BAL total protein levels (baseline n = 6–7/ group, VILI n = 7–15/ group, for both diets), *P < 0.05 by 2-way ANOVA versus control diet 8-hour VILI, with Bonferroni post-hoc test; and (F) BAL IL-6 levels (baseline n = 6–7/group, VILI n = 5/group for both diets), *P < 0.05 by 2-way ANOVA, with Bonferroni post-hoc test versus control. All data are presented as mean + SEM. No difference in baseline levels for any of these outcomes was observed between to the 2 groups prior to mechanical ventilation.