Article
Neuromodulation against resistant hypertension: Efficiency of ECG-synchronized selective vagal nerve stimulation in an acute sheep model
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Published: | June 9, 2017 |
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Objective: We recently demonstrated that constant and intermittent selective stimulation of afferent vagal nerve fibers can trigger the baroreflex and lower the blood pressure in rats. In this study we perform selective vagal nerve stimulation in an acute sheep model. Beside investigating the selectivity of the stimulation we compare the efficiency of constant vs. ECG-synchronized stimulation. ECG-synchronized stimulation not only resembles a way more physiological stimulation form, it is also more energy efficient than constant stimulation and could pave the way for an antihypertensive vagal nerve stimulator with a long lifetime.
Methods: The left vagal nerves of 3 male sheep were surgically prepared and positioned in a multichannel cuff electrode (MCE). Real-time blood pressure monitoring was achieved by an intra-arterial microtip probe in the carotid artery. First, the contacts of the MCE that caused cardiocirculatory effects were identified, and then several runs of stimulation with different amplitudes, frequencies and pulse widths were performed both in a constant and in an ECG-synchronized manner. Blood pressure and heartrate responses in relation to the applied energy were analyzed.
Results: In comparison to stimulation in rats, the heartrate responded more severely to any kind of vagal nerve stimulation on specific contacts, while other contacts did not cause any change in blood pressure or heartrate. Using constant stimulation, the strongest drop in heart rate was -32 bpm, while the highest drop in blood pressure was 40 mmHg (MAP). The average efficacy coefficient across all stimulation parameters in stationary stimulation was 1.91 mmHg/bpm. For ECG-synchronized stimulation, strongest drop in blood pressure was 17 mmHg MAP, the strongest reduction in heartrate was -7 bpm. The efficacy coefficient in pulsatile stimulation was 6.34 mmHg/bpm.
Conclusion: Selective vagal nerve stimulation in sheep causes more cardiac side effects then in rats. While constant stimulation caused the most pronounced drop in heartrate with accompanying drop in blood pressure, less bradycardia with comparable drop in blood pressure was achieved with ECG-synchronized selective vagal nerve stimulation. Differences in efficiency of constant and synchronized selective vagal nerve stimulation become obvious that may be interesting for a chronic implantation.