Effect of Cardiac-Cycle-Synchronized Selective Vagal Stimulation on Heart Rate and Blood Pressure in Rats

Plachta, Dennis T. T.; Zentner, Josef; Aguirre, Debora; Cota, Oscar; Gierthmuehlen, Mortimer

doi:10.1007/s12325-016-0348-z

Cited by 16 publications

(11 citation statements)

References 23 publications

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“…This effect is likely mediated through activation of the aortic depressor nerve which sends signals to the brain resulting in the activation of the baroreflex and a decrease in BP (Plachta et al, 2014). This acute BP reduction has been demonstrated previously where selective and non-selective VNS therapy was applied in anesthetized rats (Plachta et al, 2014, 2016).…”

Section: Discussionsupporting

confidence: 78%

“…Antiarrhythmic effects have also been recently demonstrated by our lab in healthy hearts in the absence of sympathetic overdrive (Lee et al, 2016). Further, acute VNS therapy has also shown a beneficial effect on BP and heart rate (HR) dynamics in hypertensive rats (Plachta et al, 2014, 2016; Annoni and Tolkacheva, 2018). However, to date, there has been limited research evaluating the long-term effects of VNS on BP and associated cardiovascular complications in advanced-stage HTN in rats.…”

Section: Introductionmentioning

confidence: 99%

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Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats

et al. 2019

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Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats

et al. 2019

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“…Since aVNS recruits sensory fibers to the brainstem (Figure 1), aVNS could be hypothetically expected to mimic the sensory feedback to the brain (Figure 2C), circumventing temporally a lost or impaired feedback. For instance, the invasive and selective stimulation of the cervical VN was used to mimic baroreceptor signals to lower the blood pressure in rats (Plachta et al, 2014, 2016). In analogy, the baroreflex sensitivity was improved by aVNS in humans (Antonino et al, 2017), thus affecting processing of afferent signals in the brain.…”

Section: Vagus Nerve Stimulation – From Biophysics To Animal and To Hmentioning

confidence: 99%

Current Directions in the Auricular Vagus Nerve Stimulation I – A Physiological Perspective

et al. 2019

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Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects – a discussion of engineering aspects is provided by our accompanying article ( Kaniusas et al., 2019 ). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

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“…In the dog, they demonstrated selective control of HR and respiration rate by stimulating with sets of three electrodes at different positions around the nerve circumference (Figures 3F,G; Rozman and Peclin, 2008). They then applied the same technique to two human patients, reducing the HR Plachta et al (2013Plachta et al ( , 2014Plachta et al ( , 2016, . while preferentially activating B over A fibers (Pečlin et al, 2009).…”

Section: Fiber-selective Vnsmentioning

confidence: 99%

“…(C) Pelot and Grill (2020) , Patel et al (2017) , Dali et al (2019) . (D) Plachta et al (2013 , 2014 , 2016 ), Gierthmuehlen and Plachta (2016) . (E) Aristovich et al (2021) .…”

Section: Selective Vnsmentioning

confidence: 99%

Selective Neuromodulation of the Vagus Nerve

2021

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Vagus nerve stimulation (VNS) is an effective technique for the treatment of refractory epilepsy and shows potential for the treatment of a range of other serious conditions. However, until now stimulation has generally been supramaximal and non-selective, resulting in a range of side effects. Selective VNS (sVNS) aims to mitigate this by targeting specific fiber types within the nerve to produce functionally specific effects. In recent years, several key paradigms of sVNS have been developed—spatially selective, fiber-selective, anodal block, neural titration, and kilohertz electrical stimulation block—as well as various stimulation pulse parameters and electrode array geometries. sVNS can significantly reduce the severity of side effects, and in some cases increase efficacy of the treatment. While most studies have focused on fiber-selective sVNS, spatially selective sVNS has demonstrated comparable mitigation of side-effects. It has the potential to achieve greater specificity and provide crucial information about vagal nerve physiology. Anodal block achieves strong side-effect mitigation too, but is much less specific than fiber- and spatially selective paradigms. The major hurdle to achieving better selectivity of VNS is a limited knowledge of functional anatomical organization of vagus nerve. It is also crucial to optimize electrode array geometry and pulse shape, as well as expand the applications of sVNS beyond the current focus on cardiovascular disease.

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Effect of Cardiac-Cycle-Synchronized Selective Vagal Stimulation on Heart Rate and Blood Pressure in Rats

Abstract: Introduction: Activation of the baroreflex system through the selective vagal nerve

Cited by 16 publications

References 23 publications

Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats

Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats

Current Directions in the Auricular Vagus Nerve Stimulation I – A Physiological Perspective

Selective Neuromodulation of the Vagus Nerve

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