Vagus Nerve Stimulation and the Cardiovascular System

Capilupi, Michael J; Kerath, Samantha M; Becker, Lance B.

doi:10.1101/cshperspect.a034173

Cited by 106 publications

(89 citation statements)

References 107 publications

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“…Electrocardiographic (ECG) metrics are considered to be among the most promising candidate biomarkers (Clancy et al, 2014;Gurel et al, 2020), for two reasons: Firstly, ECG is inexpensive, and quickly and safely applicable in virtually all patient subpopulations, unlike, for example, magnetic resonance imaging-based biomarkers (Mithani et al, 2019;Yakunina et al, 2017). Secondly, there is a clear physiological rationale for a relationship between taVNS and cardiac readouts, since the vagus nerve is involved in the autonomic regulation of heart rate (HR), heart rate variability (HRV) and blood pressure (BP) (Capilupi et al, 2019;Karemaker, 2015). Accordingly, animal studies have confirmed cardiac effects of (invasive) VNS (Brack et al, 2004;Brown and Eccles, 1934;Buschman et al, 2006;Iwao et al, 2000;Kuo et al, 2005;Levy et al, 1969).…”

Section: Introductionmentioning

confidence: 99%

Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects

Keute¹,

Machetanz²,

Berelidze³

et al. 2021

Brain Stimulation

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Section: Introductionmentioning

confidence: 99%

Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects

Keute¹,

Machetanz²,

Berelidze³

et al. 2021

Brain Stimulation

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“…5A). VNS can decrease chronotropy, afterload, and myocardial oxygen demand (Capilupi et al, 2020; Levy & Schwartz, 1994; Buck et al, 1981), all factors that are elevated during spontaneous myocardial ischemia (Svensson et al, 2001; Rehman et al, 1997; Deedwania & Carbajal, 1992; Hinderliter et al, 1991; Deedwania & Nelson, 1990). D+NE targets catecholamine receptors relevant for myocardial ischemia and has a maximal effect on the recorded features.…”

Section: Resultsmentioning

confidence: 99%

“…To this end, we used an ANN that rapidly decodes events of spontaneous myocardial ischemia, and responsively triggers therapeutic closed-loop vagus nerve stimulation (VNS). Responsive closed-loop VNS may be an effective bioelectronic medicine for reversing ischemia mediated elevations in chronotropy, afterload, and myocardial oxygen demand (Capilupi et al, 2020; Levy & Schwartz, 1994; Ardell et al, 2015; Buck et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Detecting and Reversing Myocardial Ischemia Using an Artificially Intelligent Bioelectronic Medicine

Ganzer

Loeian

Roof

et al. 2021

Preprint

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Myocardial ischemia is spontaneous, usually asymptomatic, and contributes to fatal cardiovascular consequences. Importantly, biological neural networks cannot reliably detect and correct myocardial ischemia on their own. Supplementing biological neural networks may enable reliable detection, and potentially even facilitate correction, of myocardial ischemia. In this study, we demonstrate an artificially intelligent and responsive bioelectronic medicine, where an artificial neural network (ANN) supplements biological neural networks enabling reliable detection and correction of myocardial ischemia (preclinical experiments in rats). This responsive bioelectronic medicine uses an ANN with a long short-term memory layer to decode spontaneous myocardial ischemia and autonomously trigger vagus nerve stimulation (VNS) for reducing chronotropy, afterload, and myocardial oxygen demand. We first used injections of cardiovascular stress inducing agents (dobutamine and norepinephrine) that produce a model of spontaneous myocardial ischemia. Next, ANNs were trained to decode spontaneous cardiovascular stress and myocardial ischemia, with an overall accuracy of ~92%. ANN-controlled VNS reversed the major biomarkers of myocardial ischemia with no side effects. In contrast, open-loop VNS or ANN controlled VNS following a caudal vagotomy essentially failed to reverse correlates of myocardial ischemia. Lastly, variants of ANNs were used to meet clinically relevant needs, including interpretable visualizations of stress pathophysiology and unsupervised detection of new emerging stress states. Together, this adaptive architecture provides clinically relevant insights as pathophysiology evolves. Overall, these results provide a first-time demonstration that ANNs can supplement deficient biological neural networks to dynamically detect and help bioelectronically reverse cardiovascular pathophysiology.

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“…The vagus nerve innervates the heart (93). Heart failure ultimately leads to a requirement for heart transplantation (94).…”

Section: Elevated Pns Activitymentioning

confidence: 99%

“…Interestingly, VNS was reported to be an effective clinical treatment for medication-resistant epileptic patients and depressed patients (75,101). However, clinical testing is still required to determine the efficacy of VNS in patients with cerebrovascular disease, as serious adverse cardiovascular effects are possible with VNS (93). In summary, PNS activation can improve clinical outcomes, and may represent a new direction for prevention and therapy of stroke-related ANS dysfunction.…”

Section: Elevated Pns Activitymentioning

confidence: 99%

The Association of Autonomic Nervous System Function With Ischemic Stroke, and Treatment Strategies

2020

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Acute ischemic stroke, especially minor stroke, and transient ischemic attack have high risks of recurrence and exacerbation into severe ischemic strokes. It remains challenging to perform risk stratification and screen high-risk groups for initiation of early treatment in these patients. Moreover, with the growing population of patients with chronic small vessel disease, the mechanisms and clinical implications require further investigation. Traditional tools such as the ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) have only moderate predictive value in patients with transient ischemic attack or minor stroke. By contrast, measurement of changes in heart rate variability (HRV) is an important and novel tool for risk stratification and outcome prediction in patients with cardiovascular diseases, as it reflects the overall level of autonomic nervous system dysfunction. Thus, abnormal HRV may be useful for prognosis and improve stratification of stroke patients with diverse risks. HRV may also partially explain autonomic nervous dysfunction and other manifestations during the process of chronic cerebral small vessel disease. In summary, measurement of HRV may contribute to early initiation of interventions in acute or chronic stroke patients using novel treatments involving rebalancing of autonomic nervous system function.

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Vagus Nerve Stimulation and the Cardiovascular System

Cited by 106 publications

References 107 publications

Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects

Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects

Detecting and Reversing Myocardial Ischemia Using an Artificially Intelligent Bioelectronic Medicine

The Association of Autonomic Nervous System Function With Ischemic Stroke, and Treatment Strategies

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