Noninvasive optogenetic induction of cardiac arrhythmias alters systemic hemodynamics in mice

Mouse models are valuable for studying the systemic effects of arrhythmia, but traditional methods of heart pacing are invasive and technically complex. Cardiac optogenetics enables precise control of cardiac activity using light-sensitive ion channels and has been used for tachypacing, resynchronization, and defibrillation in animal models. Recent advances in opsins with red-shifted activation spectra and optimized light delivery strategies have enhanced noninvasive pacing approaches, particularly in mammalian models. Here, we use an area illumination approach for light stimulation through the intact chest to perform in vivo, noninvasive optogenetic tachypacing in transgenic mice expressing ReaChR with low irradiance (<1 mW/mm 2 ). We assess both cardiac and cortical hemodynamic responses via echocardiography and optical intrinsic signal imaging (OISI). Our findings reveal that whole-heart arrhythmic stimulation alters cortical hemodynamic activity, highlighting the direct impact of arrhythmias on brain perfusion and oxygenation. This work provides insight into the heart-brain connection and the broader systemic consequences of cardiac dysfunction.