QUANTITATIVE ASSESSMENT OF TRANSIENT HEART RATE DYNAMICS IN PATIENTS EXPOSED TO CHRONIC AUTONOMIC REGULATION THERAPY PROVIDES EVIDENCE OF DURABLE NEUROMODULATION RESULTING FROM CYCLIC STIMULATION OF VAGUS NERVE

The influence of isoproterenol, norepinephrine, and dopamine on the cardiomoderator effects of moderate vagal stimulation was studied in anesthetized dogs. The drugs were administered at increasing doses in successive perfusions. Stimulation of the vagus nerve, the parameters of which remained constant throughout each experiment, was performed immediately before each sequence of perfusion and after 10-min perfusion. Isoproterenol at 0.025, 0.05, 0.1, and 0.2 microgram X kg-1 X min-1 raised heart rate dose relatedly but did not alter heart rate under vagal stimulation. Thus the amplitude of vagal bradycardic effects increased dose relatedly. Norepinephrine at 0.125, 0.25, 0.5, and 1 microgram X kg-1 X min-1 lowered heart rate through reflex hypertension. Heart rate under vagal stimulation remained constant. Thus the effects of vagal stimulation decreased as dose increased, finally becoming null. Dopamine at 0.5, 1, 2.5, and 5 micrograms X kg-1 X min-1 did not significantly alter heart rate, but at 10 and 20 micrograms X kg-1 X min-1, like norepinephrine, it raised blood pressure, causing a reflex fall in heart rate. At all doses, heart rate under vagal stimulation remained stable. Consequently, at the highest doses, the net effects of vagal stimulation were slight. These results suggest the simultaneous involvement of sympathetic-parasympathetic interactions both post- and prejunctionally. In the latter case, different mechanisms of regulation of neurotransmitter release are involved during vagal stimulation according to the sympathomimetic used. With isoproterenol, norepinephrine release seems more particularly affected, whereas with norepinephrine and dopamine, acetylcholine release is apparently inhibited.

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Accurate control of the heart rate in monkeys by burst stimulation of the vagus nerve

Bulletin of Experimental Biology and Medicine ◽

10.1007/bf00841984 ◽

1987 ◽

Vol 104 (3) ◽

pp. 1180-1182

Author(s):

V. M. Pokrovskii ◽

Yu. R. Sheikh-Zade ◽

V. M. Kruchinin ◽

T. G. Urmancheeva

Keyword(s):

Heart Rate ◽

Vagus Nerve ◽

Burst Stimulation ◽

Stimulation Of

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Stochastic vagus nerve stimulation affects acute heart rate dynamics in rats

PLoS ONE ◽

10.1371/journal.pone.0194910 ◽

2018 ◽

Vol 13 (3) ◽

pp. e0194910 ◽

Cited By ~ 8

Author(s):

Steven W. Lee ◽

Kanchan Kulkarni ◽

Elizabeth M. Annoni ◽

Imad Libbus ◽

Bruce H. KenKnight ◽

...

Keyword(s):

Heart Rate ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Heart Rate Dynamics

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Development and characterization of a chronic implant mouse model for vagus nerve stimulation

eLife ◽

10.7554/elife.61270 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ibrahim T Mughrabi ◽

Jordan Hickman ◽

Naveen Jayaprakash ◽

Dane Thompson ◽

Umair Ahmed ◽

...

Keyword(s):

Heart Rate ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Axonal Pathology ◽

Device Implantation ◽

Preclinical And Clinical Studies ◽

Stimulation Of

Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies. The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus. However, there are several unanswered mechanistic questions about the effects of chronic VNS, which require solving numerous technical challenges for a long-term interface with the vagus in mice. Here, we describe a scalable model for long-term VNS in mice developed and validated in 4 research laboratories. We observed significant heart rate responses for at least 4 weeks in 60-90% of animals. Device implantation did not impair vagus-mediated reflexes. VNS using this implant significantly suppressed TNF levels in endotoxemia. Histological examination of implanted nerves revealed fibrotic encapsulation without axonal pathology. This model may be useful to study the physiology of the vagus and provides a tool to systematically investigate long-term VNS as therapy for chronic diseases modeled in mice.

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