Force adaptation through the intravenous route in naïve mice

Figures & data

Figure 1. Outline of the experimental design. Abbreviations: E_rs, elastance of the respiratory system; i.m., intramuscularly; i.p., intraperitoneally; i.v.; intravenously; PEEP, positive end-expiratory pressure; R_rs, resistance of the respiratory system.

Figure 2. Tone (i.e., a sustained activation of the airway smooth muscle) induced by methacholine. Changes in respiratory system elastance relative to baseline (ΔE_rs) caused by 20 serial i.v. doses of saline (black) or methacholine (gray). Vertical black dotted lines, 65 s apart, indicate when doses were delivered. Only the first 3 doses and the 20^th one prior to the final higher dose are indicated for clarity. The red vertical dotted line indicates when the higher final i.v. dose was delivered. These results are also shown in Figure 3 (first ∼20 min of the upper left graph), but on a different scale. Data are means + or - SD for a n = 6. The dosing regimen was identical in females, except that all doses were twice lower.

Figure 3. The effect of tone on the methacholine-induced changes in respiratory system elastance relative to baseline (ΔE_rs). The upper left and right graphs demonstrate the actual changes in E_rs throughout the whole protocol in both males and females, respectively. Note that the scale on the y-axis is smaller in females than males. The three vertical red dotted lines from left to right indicate when: 1- the final i.v. dose of methacholine was administered; 2- the nebulized dose of isoproterenol (Iso) was administered; and 3- the deep inspiration (DI) was imposed. In the bottom graph, the max E_rs after the final dose (i.e., peak response), as well as the minimal E_rs after Iso and the DI, are compared between challenges with and without tone in each sex. Results of two-way ANOVAs are shown below the graph, which were used to evaluate the effect of tone, the combined effect of Iso and the DI, and their interaction within each sex. Asterisks are from post hoc analyses, showing significant differences between challenges with and without tone for the max response (**** is p < 0.0001). Data are means + or - SD for a n = 6.

Figure 4. The effect of tone on the methacholine-induced changes in respiratory system resistance relative to baseline (ΔR_rs). The upper left and right graphs demonstrate the actual changes in R_rs throughout the whole protocol in both males and females, respectively. Note that the scale on the y-axis is smaller in females than males. The three vertical red dotted lines from left to right indicate when: 1- the last i.v. dose of methacholine was administered; 2- the nebulized dose of isoproterenol (Iso) was administered; and 3- the deep inspiration (DI) was imposed. In the bottom graph, the max R_rs after the final dose (i.e., peak response), as well as the minimal R_rs after Iso and the DI, are compared between challenges with and without tone in each sex. Results of two-way ANOVAs are shown below the graph, which were used to evaluate the effect of tone, the combined effect of Iso and the DI, and their interaction within each sex. Asterisks are from post hoc analyses, showing significant differences between challenges with and without tone for the max response (**** is p < 0.0001). Data are means + or - SD for a n = 6.