Fig. 2.
Xylazine exacerbates fentanyl-induced changes in inspiration. (A) Graphical representation of study design. Inspiratory parameters of male and female CD-1 mice (n = 6 per group) were recorded using vivoFlow whole-body plethysmography chambers supplied with air according to the timeline. (B) Effects of different doses of xylazine or fentanyl-xylazine combinations on inspiration time. Arrows and dotted lines indicate intraperitoneal injection point. Time course of inspiration time (Ti) from 0 to 60 minutes by the treatment group. Bar graph displays the group values from t = 10–15 minutes. Females are shown as circles and males as squares. Inspiratory rates were compared via two-way ANOVA (main effect of treatment, F(7, 40) = 23.82, P < .0001; main effect of time, F(4.868, 194.7) = 24.41, P < .0001; main effect of subject, F(40, 440) = 26.01, P < .0001; time × treatment interaction, F(77, 440) = 2.841, P < .0001). Average values from t = 10–15 minutes after injection were compared via one-way ANOVA (F(7, 40) = 31.99, P < .0001) with Tukey’s post hoc test. (C) Effects of different doses of xylazine or fentanyl–xylazine combinations on PIF over time were compared by two-way ANOVA main effect of treatment, F(7, 40) = 22.59, P < .0001; main effect of time, F(4.079, 163.2) = 59.96, P < .0001; main effect of subject, F(40, 440) = 31.23, P < .0001; time × treatment interaction, F(77, 440) = 3.156, P < .0001. Bar graphs display the group values from t = 10–15 minutes (females as circles, males as squares). Average values from t = 10–15 minutes after injection were compared via one-way ANOVA (F(7, 40) = 25.36, P < .0001) with Tukey’s post hoc test. ∗P < .05, ∗∗∗∗P < .0001 versus vehicle; ⊹P < .05, ⊹⊹P < .01 versus fentanyl alone.