Different Responses to Drug Safety Screening Targets between Human Neonatal and Infantile Heart Tissue and Cardiac Bodies Derived from Human-Induced Pluripotent Stem Cells

Figure 6

Response to ß-adrenergic stimulation by ISO. (a-b) Effect of ascending ISO concentrations in single experiments with human myocardial tissue slices (HLHS: of 5 patients, left panels; TOF: of 5 patients, middle left panels) and hiPS-CBs (9 wk: , middle right panels, 16 wk: , right panels). Numbers in the graphs indicate deviations from reported overall numbers at individual experimental steps. (a) Change in force of contraction (FOC) in relation to baseline (BL). The -axis differs between myocardial tissue slices and hiPS-CBs. (b) Effect on time to peak (TTP) as well as time to 50% and 90% relaxation. Lines and error bars represent the mean and 95% CIs, respectively. The -axis is the same for all groups. (c-d) Comparison of average effect sizes of 10.6 mol/L ISO relative to baseline for inotropic ((c); FOC) and lusitropic ((d); time to 90% relaxation) response. Data are expressed as CI. Numbers above error bars indicate values <0.05 vs. HLHS (1), TOF (2), 9 wk hiPS-CBs (3), and 16 wk hiPS-CBs (4). Effect on FOC: ANOVA, ; Games-Howell post hoc: HLHS vs. TOF: ; HLHS vs. hiPS-CBs 9 wk: ; HLHS vs. hiPS-CBs 16 wk: ; TOF vs. hiPS-CBs 9 wk: ; TOF vs. hiPS-CBs 16 wk: ; and hiPS-CBs 9 wk vs. hiPS-CBs 16 wk: . Effect on time to 90% relaxation: ANOVA, , Hochberg post hoc: HLHS vs. TOF: ; HLHS vs. hiPS-CBs 9 wk: ; HLHS vs. hiPS-CBs 16 wk: ; TOF vs. hiPS-CBs 9 wk: ; TOF vs. hiPS-CBs 16 wk: ; and hiPS-CBs 9 wk vs. hiPS-CBs 16 wk: .

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