Figure 4.

Pharmacological challenge with positive and negative inotropic compounds. A, Average dose–response curves (black traces) and single measurements for several parameters obtained in isolated, spontaneously beating, aligned human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) treated with isoprenaline (left, red) and nifedipine (right, green). B, Average dose–response curves (black traces) and single measurements for several parameters obtained from monolayers of hPSC-CMs treated with isoprenaline (left, red) and nifedipine (right, green). C, Average dose–response curves (black traces) and single measurements for several parameters obtained in cardiac organoids treated with isoprenaline (left, red) and nifedipine (right, green). D, Average dose–response curves (black traces) and single measurements for several parameters obtained in engineered heart tissues treated with isoprenaline (left, red) and nifedipine (right, green). E, Average dose–response curves (black traces) and single measurements for several parameters obtained in adult rabbit cardiomyocytes treated with isoprenaline (left, red) and verapamil (right, green). Average data points (black) represent mean±standard error of the mean. For details on cell sources and cell lines, please refer to Online Table I. Data information: P values DMSO (dimethyl sulfoxide) vs dose. Ai, 0.3 nmol/L, 0.2897; 1 nmol/L, 3.4/10⁶; 3 nmol/L, 3.8/10⁸; 10 nmol/L, 7/10¹¹; 30 nmol/L, 7.3/10¹⁰; and 100 nmol/L, 2.4/10¹⁰. Aii, 0.3 nmol/L, 1; 1 nmol/L, 0.0645; 3 nmol/L, 0.0136; 10 nmol/L, 8.2/10⁵; 30 nmol/L, 0.0063; and 100 nmol/L, 2.4/10⁶. N=14; 14; 14; 14; 14; 14; 14. Aiii, 3 nmol/L, 0.6533; 10 nmol/L, 4/10⁵; 30 nmol/L, 2/10⁹; and 100 nmol/L, 1.5/10¹⁵. Aiv, 3 nmol/L, 0.00 054; 10 nmol/L, 1.9/10¹¹; 30 nmol/L, <2/10¹⁶; and 100 nmol/L, <2/10¹⁶. N=14; 14; 14; 14; 14. P values baseline vs dose. Bi, 1 nmol/L, 1; 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 1; and 300 nmol/L, 1. Bii, 1 nmol/L, 1; 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 1; and 300 nmol/L, 1. N=6; 5; 6; 6; 6; 6; 6. Biii, 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 0.00 801; 300 nmol/L, 2.7/10⁹; and 1000 nmol/L, 1.8/10¹⁰. Biv, 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 0.00 084; 300 nmol/L, 2.9/10¹¹; and 1000 nmol/L, 1.5/10¹¹. N=6; 6; 6; 6; 6; 6; 6. P values baseline vs dose. Ci, 1 nmol/L, 1; 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 1; and 300 nmol/L, 1. Cii, 1 nmol/L, 1; 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 1; and 300 nmol/L, 1. N=5; 5; 4; 5; 4; 4; 4. Ciii, 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 0.00 181; 300 nmol/L, 2.9/10⁶; and 1000 nmol/L, 1.7/10⁵. Civ, 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 0.54 836; 300 nmol/L, 0.01 392; and 1000 nmol/L, 8.2/10⁵. N=5; 5; 4; 5; 5; 5; 3. P values baseline vs dose. Di, 1 nmol/L, 1; 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 0.47; and 100 nmol/L, 1. Dii, 1 nmol/L, 0.02 318; 3 nmol/L, 0.00 170; 10 nmol/L, 0.00 028; 30 nmol/L, 0.00 044; and 100 nmol/L, 0.00 113. N=5; 5; 5; 5; 5; 5. Diii, 3 nmol/L, 1; 10 nmol/L, 1; 30 nmol/L, 1; and 100 nmol/L, 3/10⁵. Div, 3 nmol/L, 1; 10 nmol/L, 0.49 856; 30 nmol/L, 0.01 473; and 100 nmol/L, 7/10⁶. N=6; 6; 6; 6; 6. P values Krebs vs dose. Ei, 1 nmol/L, 1; 3 nmol/L, 1. Eii, 1 nmol/L, 1; and 3 nmol/L, 0.54. N=6; 10; 7. P values DMSO vs dose. Eiii, 10 nmol/L, 1; 30 nmol/L, 1; 100 nmol/L, 1; and 300 nmol/L, 1. Eiv, 10 nmol/L, 0.5298; 30 nmol/L, 0.2470; 100 nmol/L, 0.0054; and 300 nmol/L, 0.0029. N=7; 8; 4; 5; 7. *P<0.05