Spontaneous Breathing Through Increased Airway Resistance Augments Elastase-Induced Pulmonary Emphysema

Figures & data

Figure 1 BAL cell subpopulation during resistive breathing through tracheal banding in elastase-treated mice. (A) Elastase treatment resulted in a ~2-fold increase in total cell count that was not affected by resistive breathing (neither for 24 nor for 72h). Differential cell count revealed that resistive breathing (both 24 and 72h) increases neutrophil count in BAL fluid in elastase-treated mice (B), but not macrophage count (C). Data are presented as mean ± SEM, *p<0.05 to ctr (veh+sham), ^#p<0.05 to elastase (ANOVA, LSD post hoc test), white bar, veh+sham, grey bar, veh+RB24h, dark grey bar, veh+RB72h, grey bar/hatched lines, elastase, dark grey bar/hatched lines, elastase+RB24h, black bar, elastase+RB72h.

Figure 2 Respiratory system mechanics following resistive breathing in elastase-treated animals. Elastase treatment increased both dynamic and static compliance. Addition of either 24h or 72h of RB reduced compliance, when added to elastase (A and C). 72h of RB also increased total respiratory system resistance, when compared to elastase alone (B). 24h of RB increased hysteresis, whereas 72h of RB decreased hysteresis, when combined with elastase treatment (D). As expected, elastase treatment resulted in an upward shift of the Pressure-Volume curve, compared to control, suggesting the presence of emphysema, whereas resistive breathing caused a downward shift, denoting the presence of lung injury (E). Combination of elastase and RB for 72 hours caused an intermediate effect, shifting the P-V curve upward but to a lesser degree than elastase alone. (To reduce figure complexity the 24h RB time point was omitted from the P-V curve diagram). Data are presented as mean ± SEM, *p<0.05 to ctr (veh+sham), ^#p<0.05 to elastase, ^{^}p<0.05 to elastase plus RB24h (ANOVA, LSD post hoc test), white bar, veh+sham, grey bar, veh+RB24h, dark grey bar, veh+RB72h, grey bar/hatched lines, elastase, dark grey bar/hatched lines, elastase+RB24h, black bar, elastase+RB72h.

Figure 3 Pulmonary emphysema following resistive breathing in elastase-treated animals. Intratracheal elastase-induced pulmonary emphysema, as shown by the increased Lm (A) and DI (B) indices. Following 72 hours of resistive breathing, aggravated pulmonary emphysema was observed in elastase-treated mice. Representative E&H stained tissue sections (x200) of control (C), elastase (D), 24h RB (E), elastase plus 24h RB (F), 724h RB (G), elastase plus 72h RB (H) mice. Note the enlargement of alveolar airspaces and the destruction of normal lung architecture following 21 days of elastase treatment, which were further exacerbated when combined with 72hrs of RB. Data are presented as mean ± SEM, *p<0.05 to ctr (veh+sham), ^#p<0.05 to elastase, ^{^}p<0.05 to elastase plus RB24h (ANOVA, LSD post hoc test), white bar, veh+sham, grey bar, veh+RB24h, dark grey bar, veh+RB72h, grey bar/hatched lines, elastase, dark grey bar/hatched lines, elastase+RB24h, black bar, elastase+RB72h.