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Vagal nerve stimulation therapy: what is being stimulated?

Kember G, Ardell JL, Armour JA, Zamir M - PLoS ONE (2014)

Bottom Line: The therapy has shown promise but the mechanisms by which any benefit accrues is not understood.The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis.This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Mathematics, Dalhousie University, Halifax, Nova Scotia, Canada.

ABSTRACT
Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

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Related in: MedlinePlus

Model simulation under subthreshold conditions whereby the direct component of the VSC is not being activated but the indirect component and therefore the local circuit elements of the neural network are being activated at low intensity.Here, as in the experiment (Figure 2), there are no discernible changes in heart rate. Red bars indicate time intervals when VNS is on.
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pone-0114498-g007: Model simulation under subthreshold conditions whereby the direct component of the VSC is not being activated but the indirect component and therefore the local circuit elements of the neural network are being activated at low intensity.Here, as in the experiment (Figure 2), there are no discernible changes in heart rate. Red bars indicate time intervals when VNS is on.

Mentions: Subthreshold: As the level of stimulation is increased from zero in the model the effect on heart rate is barely visible, as observed in Figure 7. Here the direct component of the VSC is turned off and the indirect component is minimally stimulated as described above. We refer to this set of conditions as “subthreshold” in the sense that no qualitative changes in heart rate are discernible at this level of stimulation. It is important to point out that while the direct component of the VSC is not being activated at this level of stimulation, the indirect component of the VSC and therefore the local circuit elements of the neural network are being activated. This has important implications which will be discussed later.


Vagal nerve stimulation therapy: what is being stimulated?

Kember G, Ardell JL, Armour JA, Zamir M - PLoS ONE (2014)

Model simulation under subthreshold conditions whereby the direct component of the VSC is not being activated but the indirect component and therefore the local circuit elements of the neural network are being activated at low intensity.Here, as in the experiment (Figure 2), there are no discernible changes in heart rate. Red bars indicate time intervals when VNS is on.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257685&req=5

pone-0114498-g007: Model simulation under subthreshold conditions whereby the direct component of the VSC is not being activated but the indirect component and therefore the local circuit elements of the neural network are being activated at low intensity.Here, as in the experiment (Figure 2), there are no discernible changes in heart rate. Red bars indicate time intervals when VNS is on.
Mentions: Subthreshold: As the level of stimulation is increased from zero in the model the effect on heart rate is barely visible, as observed in Figure 7. Here the direct component of the VSC is turned off and the indirect component is minimally stimulated as described above. We refer to this set of conditions as “subthreshold” in the sense that no qualitative changes in heart rate are discernible at this level of stimulation. It is important to point out that while the direct component of the VSC is not being activated at this level of stimulation, the indirect component of the VSC and therefore the local circuit elements of the neural network are being activated. This has important implications which will be discussed later.

Bottom Line: The therapy has shown promise but the mechanisms by which any benefit accrues is not understood.The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis.This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Engineering Mathematics, Dalhousie University, Halifax, Nova Scotia, Canada.

ABSTRACT
Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Show MeSH
Related in: MedlinePlus