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Overview of the neurocardiac axis and invasive neuromodulatory approaches. CVLM, caudal ventrolateral medulla; DVN, dorsal vagal nucleus; IML, intermediolateral cell column; NTS, nucleus of the solitary tract; RVLM, rostroventrolateral medulla.
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Autonomic imbalance plays a crucial role in the genesis and maintenance of cardiac disorders. Approaches to maintain sympatho-vagal balance in heart diseases have gained great interest in recent years. Emerging therapies However, certain types of emerging therapies including direct electrical stimulation and nerve denervation require invasive impla...
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The autonomic nervous system (ANS) is known to play an important role in the genesis and maintenance of atrial fibrillation (AF). Biomolecular and genetic mechanisms, anatomical knowledges with recent diagnostic techniques acquisitions, both invasive and non‐invasive, have enabled greater therapeutic goals in patients affected by AF related to ANS...
Citations
... Imbalance in ANS, when persists, is known as a preceding factor for many disorders [4][5][6]. This is also true for CVDs as many studies have shown the association between an imbalance in cardiovascular ANS function and developing hypertension, heart failure, arrhythmias, and acute myocardial infarction [7][8][9][10]. Therefore, regulating cardiovascular autonomic function in apparently healthy subjects seems to be a promising strategy for preventing future CVDs. ...
... Cardiovascular ANS can be modulated by pharmacological and nonpharmacological methods. In recent years, nonpharmacologic approaches to treat CVDs draw more interest because of the limited efficacy, fewer adverse side effects, and the significant costs of pharmacological agents [8,10,11]. Nonpharmacological methods are comprised of invasive and noninvasive therapies. Invasive techniques consist of low-level vagus nerve stimulation (VNS) [12], low-level baroreceptor activation therapy [13], spinal cord stimulation [14], ganglionated plexi ablation [15], renal sympathetic denervation [16], and cardiac sympathetic nerve denervation [17]. ...
... Invasive techniques consist of low-level vagus nerve stimulation (VNS) [12], low-level baroreceptor activation therapy [13], spinal cord stimulation [14], ganglionated plexi ablation [15], renal sympathetic denervation [16], and cardiac sympathetic nerve denervation [17]. Noninvasive approaches generally use electrical pulses, electromagnetic field, ultrasound energy, and optogenetics to transcutaneously target cardiovascular ANS [10,18]. ...
Purpose:
This systematic review aimed to evaluate the effect of transcutaneous auricular vagus nerve stimulation on heart rate variability and baroreflex sensitivity in healthy populations.
Method:
PubMed, Scopus, the Cochrane Library, Embase, and Web of Science were systematically searched for controlled trials that examined the effects of transcutaneous auricular vagus nerve stimulation on heart rate variability parameters and baroreflex sensitivity in apparently healthy individuals. Two independent researchers screened the search results, extracted the data, and evaluated the quality of the included studies.
Results:
From 2458 screened studies, 21 were included. Compared with baseline measures or the comparison group, significant changes in the standard deviation of NN intervals, the root mean square of successive RR intervals, the proportion of consecutive RR intervals that differ by more than 50 ms, high-frequency power, low-frequency to high-frequency ratio, and low-frequency power were found in 86%, 75%, 69%, 47%, 36%, and 25% of the studies evaluating the effects of transcutaneous auricular vagus nerve stimulation on these indices, respectively. Baroreflex sensitivity was evaluated in six studies, of which a significant change was detected in only one. Some studies have shown that the worse the basic autonomic function, the better the response to transcutaneous auricular vagus nerve stimulation.
Conclusion:
The results were mixed, which may be mainly attributable to the heterogeneity of the study designs and stimulation delivery dosages. Thus, future studies with comparable designs are required to determine the optimal stimulation parameters and clarify the significance of autonomic indices as a reliable marker of neuromodulation responsiveness.
... PNS and the SNS were activated by acupuncture needling at Hegu (LI4) and Neiguan (PC6) [48]. In addition, some non-invasive autonomic neuromodulation techniques for treating cardiovascular diseases include transcutaneous auricular vagus nerve stimulation, electromagnetic field stimulation, ultrasound stimulation, optogenetics for stimulation and transcutaneous cervical nerve stimulation [49]. In this study, photobiostimulation was used. ...
(1) Background: The imbalance of the autonomic nervous system (ANS) is common worldwide. Many people have high tension when the sympathetic nervous system is hyperactive or low attention when the parasympathetic nervous system is hyperactive. To improve autonomic imbalance, a feasible and integrated system was proposed to measure and affect the ANS status. (2) Methods: The proposed system consists of a signal-processing module, an LED stimulation module, a photoplethysmography (PPG) sensor and an LCD display. The heart rate variability (HRV) and ANS status can be analyzed from PPG data. To confirm HRV analysis from PPG data, an electrocardiogram (ECG) device was also used to measure HRV. Additionally, photobiomodulation (PBM) was used to affect the ANS status, and two acupuncture points (Neiguan (PC6) and Shenmen (HT7)) were stimulated with different frequencies (10 Hz and 40 Hz) of PBM. (3) Results: Two subjects were tested with the developed system. HRV metrics were discussed in the time domain and frequency domain. HRV metrics have a similar change trend on PPG and ECG signals. In addition, the SDNN was increased, and the parasympathetic nervous system (PNS: HF (%)) was enhanced with a 10 Hz pulse rate stimulation at the Neiguan acupoint (PC6). Furthermore, the SDNN was increased, and the sympathetic nervous system (SNS: LF (%)) was enhanced with a 40 Hz pulse rate stimulation at the Shenmen (HT7) acupoint. (4) Conclusion: A prototype to measure and affect the ANS was proposed, and the functions were feasible. The test results show that stimulating the Neiguan (PC6) acupoint can inhibit the SNS. In contrast, stimulating the Shenmen (HT7) acupoint can activate the SNS. However, more experiments must be conducted to confirm the effect by choosing different pulse rates, dosages and acupoints.
... Neuromodulation with electrical nerve stimulation has come progressively into focus as a treatment option for various chronic diseases to change end-organ function through systemic effects on the human body (Chen et al., 2020;Cirillo et al., 2022;Kaniusas et al., 2019a). Stimulation affects multiple immunological, physiological, psychometric, and biochemical functions (Tracey, 2007;Krzyzaniak et al., 2011;Mercante et al., 2018). ...
... In the case of cardiovascular diseases, increased vagal activity has been observed to reduce vascular inflammation and cardiovascular risk in patients and animal models [40,41]. Thus, noninvasive electrical stimulation for the treatment of cardiovascular disorders offers a very active new field of research [42]. Moreover, in patients with rheumatoid arthritis treated with a device that electronically stimulates the left cervical vagus nerve, TNFα production and disease severity were reduced [36]. ...
In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation.
A life-threatening illness that poses a serious threat to human health is myocardial infarction. It may result in a significant number of myocardial cells dying, dilated left ventricles, dysfunctional heart function, and ultimately cardiac failure. Based on the development of emerging biomaterials and the lack of clinical treatment methods and cardiac donors for myocardial infarction, hydrogels with good compatibility have been gradually applied to the treatment of myocardial infarction. Specifically, based on the three processes of pathophysiology of myocardial infarction, we summarized various types of hydrogels designed for myocardial tissue engineering in recent years, including natural hydrogels, intelligent hydrogels, growth factors, stem cells, and microRNA-loaded hydrogels. In addition, we also describe the heart patch and preparation techniques that promote the repair of MI heart function. Although most of these hydrogels are still in the preclinical research stage and lack of clinical trials, they have great potential for further application in the future. It is expected that this review will improve our knowledge of and offer fresh approaches to treating myocardial infarction.
Stress can trigger cardiovascular disease. Both imbalance of autonomic nervous activity and increase of neurohormonal output are core aspects of stress responses and can lead to cardiovascular disease. PC6 as a very important acupoint is used to prevent and treat cardiovascular disease and to improve stress-related activities. We examined the influence of electroacupuncture (EA) at PC6 on stress-induced imbalance of autonomic nervous activity and increase of neurohormonal output. EA at PC6 relieved increased cardiac sympathetic nervous activity and decreased cardiac vagal nervous activity induced by immobilization stress. Also, EA at PC6 reduced immobilization stress-induced increases of plasma norepinephrine (NE) and adrenaline (E) released from sympatho-adrenal-medullary axis. Finally, EA at PC6 reduced immobilization stress-induced increases of corticotropin-releasing hormone (CRH) in paraventricular hypothalamic nucleus and plasma cortisol (CORT) released from hypothalamic-pituitary-adrenal axis. However, EA at tail had no significant effect on the stress-induced autonomic and neuroendocrine responses. The results demonstrate the role of EA at PC6 regulating the autonomic and neuroendocrine responses induced by stress and provide insight into the prevention and treatment of EA at PC6 for stress-induced cardiovascular disease by targeting autonomic and neuroendocrine systems.
The imbalance between the sympathetic and the parasympathetic nervous system is one of the main pathogeneses of myocardial infarction (MI). Vagus nerve stimulation (VNS), which restores autonomic nervous balance by enhancing the parasympathetic drive, is shown to have benefits for patients with MI. As a clinically safe and effective remote neuromodulation method, magnetic stimulation is expected to overcome the problems of infection and nerve injury caused by electrode implantation. However, it is difficult to achieve precise stimulation on a single vagus nerve due to the poor focus of the magnetic field. Here, we described a novel magnetic vagus nerve stimulation (mVNS) system, which consisted of an injectable chitosan/β-glycerophosphate (CS/GP) hydrogel loaded with superparamagnetic iron oxide (SPIO) nanoparticles and a mild magnetic pulse sequence. The injectable hydrogel prepared from clinically safe materials ensured minimally invasive implantation, and the SPIO nanoparticles in the hydrogel mediated the precise magnetic stimulation of a single vagus nerve. Under a mild magnetic field (∼100 mT), a decrease in heart rate and a change in vagus nerve potential were found in rats under in situ injection of a magnetic CS/GP hydrogel. Magnetic stimulation on the vagus nerve for 4 weeks (20 Hz, three times daily, 5 minutes each time) significantly improved the cardiac function and reduced the infarct size of the rats subjected to myocardial infarction, accompanied by suppression of inflammatory cell infiltration and inflammation factor expression. Taken together, these results demonstrated that the mVNS exhibited promising potential for treating myocardial infarction in the clinic.
Objectives:
This study aims to determine the effect of low-intensity focused ultrasound (LIFU) in ischemic heart failure (IHF) and explore the potential neuroimmune mechanism.
Methods:
Sprague-Dawley rats were subjected to ultrasound (US) with specific parameters, and electrocardiograms were recorded to analyze the effect of LIFU and/or vagal denervation on heart rate. Thereafter, myocardial infarction (MI) was induced by left anterior artery ligation, and LIFU was performed three times a day for 25 days after MI. Echocardiography, Masson staining, and ELISA were used to evaluate the effect of LIFU on the structure and function of the heart. Finally, ELISA, flow cytometry, qRT-PCR, and Western blot analysis were performed to determine the effect of LIFU on the inflammation and the expression of the cholinergic anti-inflammatory pathway (CAP)-related mediators.
Results:
LIFU reduced heart rate in rats (control vs LIFU, P < .01), and vagotomy (VT) eliminated this effect of LIFU on heart rate (VT vs LIFU + VT, P > .01). LIFU-ameliorated IHF in terms of cardiac structure and function (MI vs MI + LIFU, P < .01), but VT abrogated the beneficial effect of LIFU (MI + VT vs MI + LIFU + VT, P > .01). After the treatment of LIFU, decreased levels of inflammatory cytokines, increased proportion of anti-inflammatory macrophages, and increased expression of CAP-related mediators (MI vs MI + LIFU, P < .01).
Conclusions:
LIFU ameliorates IHF whereas the CAP plays a promising role. LIFU has the potential to be a novel nonpharmacological and noninvasive therapy for the treatment of coronary artery disease and other cardiovascular diseases.
In recent years, electromagnetic field (EMF) therapy has gathered much attention for its protective effects on cardiovascular functions. From reviewing the literature, it is evident that exposure to specific EMF spectrums, such as static- and extremely low frequency (ELF)- EMFs, by EMF-generating devices can be considered as a safe method for therapeutic means in various cardiovascular diseases, including heart failure, cardiac arrhythmias, and hypertension. This review article will describe registered patents and non-invasive clinically effective devices that generate EMF to target various cardiovascular diseases based on their mechanism of therapeutic effects.
