Invasive Optical Pacing in Perfused, Optogenetically Modified Mouse Heart Using Stiff Multi-LED Optical Probes

We present the first invasive use of a stiff, multiLED optical probe for intramural optical stimulation of cardiac tissue. We demonstrate that optical pacing is possible with high spatial and temporal resolution in transgenic mice expressing channelrhodopsin-2. The technical implementation of this study builds on optical probes recently developed and tested ex vivo in cerebral tissue of mice. The probes comprise LEDs integrated on flexible substrates stiffened by silicon-based MEMS structures enabling the successful penetration into the cardiac tissue. The probe technology is extended to allow dual-sided illumination for directional tissue stimulation. Implantation trials affirm the ability to optically pace the isolated perfused heart at stimulation frequencies between 4Hz and 12Hz with experimentally determined emittance levels of 10mW mm-2 Rapid activation of two distant LEDs could reliably be used to induce short runs of ventricular fibrillation, while simultaneous activation of all LEDs allowed termination of re-entrant rhythm disturbances (optical defibrillation). Thus, spatially-resolved intramural pacing and rhythm control of the isolated heart is possible using stiff, multi-LED optical probes.