Conduction and contraction properties of human iPS cell-derived cardiomyocytes: analysis by motion field imaging compared with the guinea-pig isolated heart model

We used motion field imaging to characterize the conduction and contraction of a sheet of cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs). A hiPS-CMs sheet of 2.8 mm × 2.8 mm allowed us to simultaneously measure the conduction and the contraction properties in the same cells. Pharmacological responses in the hiPS-CMs of four typical cardiac functional modulators, Na+ channel blocker (lidocaine), Ca2+ channel blocker (diltiazem), gap-junction inhibitor (carbenoxolone), and β-adrenergic stimulator (isoproterenol), were investigated, and the results were compared to those found using the isolated guinea-pig heart model perfused by the Langendorff method. The conduction speed of excitation waves in hiPS-CMs was decreased by lidocaine, diltiazem, and carbenoxolone, and increased by isoproterenol, and these results were in accordance with the changes in the conduction parameters of electrocardiogram (QRS duration, PR interval, and P duration) in the Langendorff guinea-pig heart model. The maximum speeds for contraction and relaxation, which respectively represent the contraction and relaxation kinetics of hiPS-CMs, were decreased by lidocaine and diltiazem, and increased by isoproterenol. These results also corresponded to alterations in the contractile and relaxation parameters found by measuring left ventricular pressure (LVdP/dtmax and LVdP/dtmin) in the Langendorff guinea-pig heart model. From these lines of evidence, it was suggested that hiPS-CMs enable us to evaluate the cardiac toxicities associated with conduction disturbance or contractile dysfunction, and thereby would be useful as an integrated assessment of cardiac function.