Registration of NADH Photobleaching for Metabolism–Excitation–Contraction Coupling Studies in Layers of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

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Abstract Investigation of the complex interrelationships of multiple intercellular processes underlying cardiac electrophysiology and pathophysiology requires the dynamic and non-invasive assessment of multiple parameters. Here, we introduce an approach to two-parametric optical mapping, which allows for studying metabolism–excitation–contraction coupling in human heart tissue. We applied this methodology for cardioplegic solution cardiotoxicity testing and to study the modulation of cardiac physiology during hypoxia. Using this approach, we determined the effects of Normacor and Custodiol cardioplegic solutions on human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) physiology with possible long-term effects on cardiomyocyte excitability. We revealed a reversible shortening of the action potential during hypoxia with Normacor (326 ± 36 ms in control and 198 ± 41 ms immediately after 4-h hypoxia and hyperkalemia) and observed an irreversible loss of excitability after 4 h of hypoxia under cold ischemia.

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