Opsin spectral sensitivity determines the effectiveness of optogenetic termination of ventricular fibrillation in the human heart: a simulation study

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp7190-list-0001">Optogenetics‐based defibrillation, a theoretical alternative to electrotherapy, involves expression of light‐sensitive ion channels in the heart (via gene or cell therapy) and illumination of the cardiac surfaces (via implanted LED arrays) to elicit light‐induced activations.We used a biophysically detailed human ventricular model to determine whether such a therapy could terminate fibrillation (VF) and identify which combinations of light‐sensitive ion channel properties and illumination configurations would be effective.Defibrillation was successful when a large proportion (> 16.6%) of ventricular tissue was directly stimulated by light that was bright enough to induce an action potential in an uncoupled cell.While illumination with blue light never successfully terminated VF, illumination of red light‐sensitive ion channels with dense arrays of implanted red light sources resulted in successful defibrillation.Our results suggest that cardiac expression of red light‐sensitive ion channels is necessary for the development of effective optogenetics‐based defibrillation therapy using LED arrays.