Research Alert
Cardiac arrhythmias are a leading cause of mortality, yet current in-vitro models used to investigate cardiac reentry allow for only limited control of arrhythmia parameters and morphology. These criteria are crucial for developing a better understanding of reentrant phenomena, and a technique that permits precise control over these parameters will lead to greater accuracy in modelling cardiac arrhythmias. To develop a method for the induction of morphologically and physiologically defined arrhythmias in human induced pluripotent stem cell derived cardiac cell sheets (hiPSC-CCSs) using optogenetics. One million hiPSC derived cardiomyocytes expressing the optogenetic channel CoChR were plated as a cell sheet. Typical rotor patterns were optically recorded and converted into image series. A digital micro mirror device (DMD) and a 470nm LED were used to project five complete cycles of these rotor patterns at physiological speeds onto the cell sheets. diffuse light was used to cardiovert the tissue after each experiment. Optical projection of rotors led to arrhythmias in all the of the tested tissues (n=8). The sustained arrhythmias within the tissues strongly resembled the projected patterns in curvature and speed, and directionality was conserved in all cases (Figure, a-c). Lastly, two-core rotor patterns were projected onto the hiPSC-CCSs resulting in a stable two-core arrhythmia being generated (Figure, d-e). Utilizing optogenetic CMs, we present a new method for the optical induction of arrhythmias with excellent precision and control over complex electrophysiological parameters. Using this technique, rotors can be induced rapidly and repeatably, with near identical morphology each time. We anticipate this method will allow for greater understanding of the delicate interplay between underlying tissue characteristics and stable rotor parameters.Background
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