Fig. 3.
Continuous infusion of 3,4-DAP has both symptomatic and antidotal effects in lethally intoxicated rats. Catheterized rats were intoxicated by intravenous injection of 2.5 LD50 BoNT/A. At 27 h after intoxication, continuous infusion was started with saline vehicle (n = 14) or 3,4-DAP at 0.5 mg/kg∙h (n = 8), 1.0 mg/kg∙h (n = 10) or 1.5 mg/kg∙h (n = 8). Toxic signs, weight and survival were monitored at 6–24 h intervals. Colors are consistent among panels A-E. Gray boxes represent infusion period. A Summary of experimental strategy. B Toxic signs at start of infusion. Data are presented as median ± IQR. C Kaplan–Meier survival curves for each treatment group. D Median toxic signs for each group over time. For panels C and D, significance indicators show pairwise comparisons made to vehicle. E Mean ± SD normalized body weights for survivors in 1.0 mg/kg∙h and 1.5 mg/kg∙h treatment groups. F Median ± IQR toxic signs for rats (n = 3) infused from 1 to 5 d with 1.5 mg/kg∙h 3,4-DAP. Treatment was withdrawn at 5 d and toxic signs were monitored at 6 h intervals. ****p < 0.0001, *p < 0.05