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Objective: This study explored intraneural stimulation of the right thoracic vagus nerve (VN) in sexually mature male minipigs to modulate safe heart rate and blood pressure response. Material and Methods: We employed an intraneural electrode designed for the VN of pigs to perform VN stimulation (VNS). This was delivered using different numbers of contacts on the electrode and different stimulation parameters (amplitude, frequency, and pulse width), identifying the most suitable stimulation configuration. All the parameter ranges had been selected from a computational cardiovascular system model. Results: Clinically relevant responses were observed when stimulating with low current intensities and relatively low frequencies delivered with a single contact. Selecting a biphasic, charge-balanced square wave for VNS with a current amplitude of 500 mu A, frequency of 10 Hz, and pulse width of 200 mu s, we obtained heart rate reduction of 7.67 +/- 5.19 beats per minute, systolic pressure reduction of 5.75 +/- 2.59 mmHg, and diastolic pressure reduction of 3.39 +/- 1.44 mmHg. Conclusion: Heart rate modulation was obtained without inducing any observable adverse effects, underlining the high selectivity of the intraneural approach.