Fig. 3.

Dose-dependent effects of 3,4-DAP on respiratory parameters and blood gas levels. Mice were challenged with 2.2x LD₅₀ BoNT/A (i.v.) and monitored for respiratory signs of botulism. Following baseline recordings, mice were treated s.c. with vehicle (n = 6) or 3,4-DAP at 0.125 mg/kg (n = 11), 0.25 mg/kg (n = 12), 0.50 mg/kg (n = 10), or 2.0 mg/kg (n = 17). (A–C) Ventilatory parameters were measured for 90 minutes after treatment, normalized to baseline values for each mouse, and reported as mean MV (A), TV (B), and RR (C). Solid lines represent time points that are significantly different than vehicle (P < 0.05; repeated measures two-way ANOVA with Dunnett’s multiple comparison test against vehicle). (D) Mean area-under-the-curve values for MV, TV, and RR peaks were plotted against 3,4-DAP dose and fit with a nonlinear regression. The resulting goodness-of-fit values (R²) are presented above each fit. (E–H) Blood gas measurements of pCO₂ (E), pH (F), HCO₃⁻ (G), and lactate (H) were made at 30 and 45 minutes after treatment. Details of statistical comparisons are provided in Supplemental Table 1. **P < 0.01; ***P < 0.001; ****P < 0.0001. ns, not significant.