FIGURE 5.

Cisapride effects on cardiac MPS and DDI in integrated liver and cardiac MPSs. (A) Cisapride-induced changes in cAPD₈₀ in the cardiac MPS. Nonlinear regression fit log(inhibitor) vs. response (Hill Equation using three parameters) was used to obtain EC₅₀ value (9.63 nM, gray vertical line). Cisapride values were corrected for PDMS drug absorption of 64%. Statistical differences are based on one-way ANOVA (p values: * = 0.0259 and ** = 0.0095). (B) Cisapride-induced changes in beat shape plotted as triangulation value (cAPD₈₀ - cAPD₃₀)/cAPD₈₀. Cisapride values are corrected for PDMS drug absorption of 64%. Statistical differences are based on one-way ANOVA (p values: * = 0.0174, ** = 0.048, *** = 0.0004 and **** <0.0001). (C) Effect of increasing concentrations of cisapride on cAPD₉₀ in the cardiac MPS. The cAPD₉₀ values of the treatments were normalized to the respective values for vehicle controls. Data are presented as the mean ± standard error of mean for at least six independent experiments. Ordinary one-way ANOVA with Dunnett’s correction for multiple comparisons test, ***p < 0.0001. Cisapride values are corrected for PDMS drug absorption of 64%. (D) Effect of cisapride metabolized in liver MPS on cAPD₉₀ in cardiac MPS. cAPD₉₀ values of the treatments were normalized to the 0 nM control values. Data are presented as the mean ± standard error of mean for three experiments. Unpaired Student’s t test with equal standard deviation was used, *p < 0.05. Cisapride values are corrected for PDMS drug absorption of 64%.