Abstract 15219: Optogenetic “Printing” of Reentrant Arrhythmias in Human Induced Pluripotent Stem Cell Derived Cardiac Tissues

Abstract

Introduction: Current models used to investigate reentrant arrhythmias allow for limited control of arrhythmia parameters and morphology. Here, we developed a method for the induction of morphologically and physiologically defined arrhythmias using human induced pluripotent stem cell derived cardiac cell sheets (hiPSC-CCSs) and optogenetic tools. Methods: One million hiPSC-cardiomyocytes expressing the optogenetic channel CoChR were used to create the hiPSC-CCSs. Rotor illumination patterns were generated either by computer-aided design or by utilizing previously recorded rotor patterns. A digital micro mirror device (DMD) and a 470nm LED were used to project five complete cycles of these rotor patterns onto the hiPSC-CCSs. Results: Optical projection of typical rotors led to repeated development of arrhythmias in all sampled tissues (n=11). The resulting arrhythmias resembled the projected rotor patterns in terms of directionality (clockwise or counterclockwise) and number of cores ,and were highly reproducible for each projection (Fig.1A). Interestingly, we identified a minimal and maximal frequency of the projected rotor that could induce arrhythmias (Fig.1B). Moreover, the frequency of the generated rotor could not be increased beyond a certain value despite further increases in the projected rotor frequency (Fig.1B). Lastly, to assess the effects of tissue EP properties, the process was repeated after treatment with the IKr blocker E-4031 (30nM). E-4031 treatment significantly reduced the minimal and maximal frequencies of the projected rotor that could still induce arrhythmia and slowed the maximal frequency of the resulting rotor (Fig.1B). Conclusions: We present a new method for the optical induction of reentrant arrhythmias allowing the generation of rotors rapidly, reproducibly, and with a predesigned morphology. This approach may allow for a paradigm shift in the way reentrant arrhythmias are studied.