Abstract

Introduction: Cardiovascular science has greatly benefited from bioelectronics and genetic engineering. However, combinations of these approaches have been hampered by challenges in genetic engineering of large animals and implantation of cardiac devices in rodents. New surgical approaches to reliably interface bioelectronics to the heart with minimal disruption to the native physiology are necessary for validation of novel bioelectronics therapies and bioelectronics-enabled in vivo studies of physiology. Objective: To develop an effective and reproducible surgical approach to implant epicardial devices in rodents. Methods: All rat surgeries (n = 138) were performed according to protocols approved by The George Washington University Institutional Animal Care and Use Committee. Inhaled isoflurane vapors provided general anesthesia. After orotracheal intubation, an intercostal incision was made and retracted in order to view the target cardiac implantation area (a). The electrode pad of a novel leadless battery-free pacemaker (b) was sutured or attached by bioadhesive to the epicardium with the device body placed subcutaneously. The ribs, muscle, and skin were subsequently closed. Post-operative care included injectable analgesics. Daily pacing trials confirmed device functionality. Results: Rats survive and quickly recover from the operation without complications. Electrocardiograms reveal that implanted miniature battery-free cardiac pacemakers pace the heart for up to 32 days after surgery (c). Echocardiography and assessment of biomarkers demonstrate no disruption to mechanical function (d) and no evidence of myocardial ischemia (e) or heart failure (f), respectively. Conclusions: This surgical technique reliably implants epicardial devices in rodents. It has broad applications to verify the long-term functionality and biocompatibility of innovative bioelectronics and to conduct in vivo studies of cardiovascular physiology.

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