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The neural stimulation of the vagus nerve is able to modulate various functions of the parasympathetic response in different organs. The stimulation of the vagus nerve is a promising approach to treating inflammatory diseases, obesity, diabetes, heart failure, and hypertension. The complexity of the vagus nerve requires highly selective stimulation, allowing the modulation of target-specific organs without side effects. Here, we address this issue by adapting a neural stimulator and developing an intraneural electrode for the particular modulation of the vagus nerve. The neurostimulator parameters such as amplitude, pulse width, and pulse shape were modulated. Single-, and multi-channel stimulation was performed at different amplitudes. For the first time, a polyimide thin-film neural electrode was designed for the specific stimulation of the vagus nerve. In vivo experiments were performed in the adult minipig to validate to elicit electrically evoked action potentials and to modulate physiological functions, validating the spatial selectivity of intraneural stimulation. Electrochemical tests of the electrode and the neurostimulator showed that the stimulation hardware was working correctly. Stimulating the porcine vagus nerve resulted in spatially selective modulation of the vagus nerve. ECAP belonging to alpha and beta fibers could be distinguished during single- and multi-channel stimulation. We have shown that the here presented system is able to activate the vagus nerve and can therefore modulate the heart rate, diastolic pressure, and systolic pressure. The here presented system may be used to restore the cardiac loop after denervation by implementing biomimetic stimulation patterns. Presented methods may be used to develop intraneural electrodes adapted for various applications.

The objective of this study was to characterize hemodynamic changes during trans-vascular stimulation of the renal nerve and their dependence on stimulation parameters. We employed a stimulation catheter inserted in the right renal artery under fluoroscopic guidance, in pigs. Systolic, diastolic and pulse blood pressure and heart rate were recorded during stimulations delivered at different intravascular sites along the renal artery or while varying stimulation parameters (amplitude, frequency, and pulse width). Blood pressure changes during stimulation displayed a pattern more complex than previously described in literature, with a series of negative and positive peaks over the first two minutes, followed by a steady state elevation during the remainder of the stimulation. Pulse pressure and heart rate only showed transient responses, then they returned to baseline values despite constant stimulation. The amplitude of the evoked hemodynamic response was roughly linearly correlated with stimulation amplitude, frequency, and pulse width., (© 2024 The Authors.)