Closed-loop electrical block of vagus nerve scales from rodent to porcine cardiac models.

. Direct current (DC) electrical block of the vagus nerve has shown the ability to downregulate the parasympathetic input to the heart. Previous investigations used static prescribed values, but the main advantage of electrical nerve block is the ability to modulate the block effect in real time. Here we investigate the potential of real-time, closed loop control of heart rate (HR), and how these control schemes translate across species.In anesthetized rats and pigs, proximal vagus stimulation was applied as a perturbation to simulate overactive vagal activity, causing a decrease in HR. DC nerve block was applied distally to mitigate this perturbation and raise HR. The block amplitudes applied were normalized to a block threshold (BT), or the amount of current to block the nerve completely in 60 s. Two static levels of 10% and 50% BT were compared to a closed-loop controlled current.In both the rat and the pig models, the closed-loop nerve block was able to control the HR to the desired setpoint (SP). Neither of the static values were able to achieve a reliably consistent level of block, with the controlled trials showing a much tighter spread of HR over time. In the pigs, a higher-gain controller was able to reach the SP more quickly. In the rat, the controller reduced both the injected charge and the time to recovery after block. In the pig, the charge was increased, but near-instant recovery times were retained. A closed-loop system is required for precision control of cardiac output.Both the rat and pig models showed success in closed-loop control of HR. Translating from rat to pig models only required minor changes to the controller, indicating that the system is robust. The ease of this translation effort bodes well for potential future translation to human therapies.