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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 sympathetic threshold conditions whereby the direct component of the VSC is not being activated but the indirect component is being activated at higher intensity than that in Figure 7.Pronounced tachycardia is observed, similar to that seen in the experiment under moderate intensity stimulation (Figure 3). Red bars indicate time intervals when VNS is on.
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pone-0114498-g008: Model simulation under sympathetic threshold conditions whereby the direct component of the VSC is not being activated but the indirect component is being activated at higher intensity than that in Figure 7.Pronounced tachycardia is observed, similar to that seen in the experiment under moderate intensity stimulation (Figure 3). Red bars indicate time intervals when VNS is on.

Mentions: Sympathetic Threshold: As the level of stimulation is increased above the subthreshold level, but with the direct component of the VSC remaining OFF, a significant tachycardia occurs as shown in Figure 8. Within the construct of the model, this is clearly because we have chosen to make the indirect component of the VSC dominant over the direct element. For this reason we refer to this choice of relative influence of the two pathways as the “sympathetic threshold”, as indicated in the figure. It is important to note that the term “sympathetic threshold” is here not intended to imply that the sympathetic network is being directly stimulated at this point but rather that the response to the twin effects of a reduced feedback to heart rate neurons at the cardiac level and increased demand to blood demand neurons at the central level is being dominated by the sympathetic network.


Vagal nerve stimulation therapy: what is being stimulated?

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

Model simulation under sympathetic threshold conditions whereby the direct component of the VSC is not being activated but the indirect component is being activated at higher intensity than that in Figure 7.Pronounced tachycardia is observed, similar to that seen in the experiment under moderate intensity stimulation (Figure 3). 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-g008: Model simulation under sympathetic threshold conditions whereby the direct component of the VSC is not being activated but the indirect component is being activated at higher intensity than that in Figure 7.Pronounced tachycardia is observed, similar to that seen in the experiment under moderate intensity stimulation (Figure 3). Red bars indicate time intervals when VNS is on.
Mentions: Sympathetic Threshold: As the level of stimulation is increased above the subthreshold level, but with the direct component of the VSC remaining OFF, a significant tachycardia occurs as shown in Figure 8. Within the construct of the model, this is clearly because we have chosen to make the indirect component of the VSC dominant over the direct element. For this reason we refer to this choice of relative influence of the two pathways as the “sympathetic threshold”, as indicated in the figure. It is important to note that the term “sympathetic threshold” is here not intended to imply that the sympathetic network is being directly stimulated at this point but rather that the response to the twin effects of a reduced feedback to heart rate neurons at the cardiac level and increased demand to blood demand neurons at the central level is being dominated by the sympathetic network.

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