The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases

Bellocchi, Chiara; Carandina, Angelica; Montinaro, Beatrice; Targetti, Elena; Furlan, Ludovico; Rodrigues, Gabriel Dias; Tobaldini, Eleonora; Montano, Nicola

doi:10.3390/ijms23052449

Cited by 46 publications

(37 citation statements)

References 162 publications

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“…Another possible explanation of sympathetic overactivity observed in MG patients may be associated with diminished central autonomic regulation in the BRS. Studies indicate that decreased baroreflex sensitivity may contribute to cardiac conduction abnormalities as well as increased risk for cardiovascular diseases through an impairment of the cholinergic anti-inflammatory pathway [42]. In our study, we showed that older age and greater disease severity turned out to be predictors of lower BRS.…”

Section: Discussionsupporting

confidence: 55%

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Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability

Zawadka‐Kunikowska

Rzepiński²,

Tafil-Klawe

et al. 2022

JCM

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Introduction: The aim of the study was to assess cardiac and autonomic function in patients with myasthenia gravis (MG) and to explore its relationship with disease outcomes. Methods: Thirty-eight patients with an MG were enrolled (median age 40.5 years; median disease duration 5.5 years). Cardiovascular parameters, baroreflex sensitivity (BRS), spectral indices of short-term heart rate (HRV), and systolic blood pressure variability (SBPV) were compared with age- and gender-matched controls (n = 30). Cardiac autonomic function was assessed during the response to standing (tilt) and deep breathing tests (expiration/inspiration ratio-E/I). Results: HR and BP responses to the tilt test were similar in both groups. MG patients, as compared to controls, were characterized by altered SBPV at rest, significantly reduced HR response to the deep breathing test (p < 0.001), increased sympathovagal balance after tilt (delta LF/HF-RRI, p = 0.037), and lower values of BRS (p = 0.007) and hemodynamic parameters, i.e., cardiac index, index contractility, left ventricular work index, at rest and during tilt. There was no association between disease duration and autonomic parameters. Disease severity, as determined by MGFA (Myasthenia Gravis Foundation of America) corrected for age and sex, was an independent predictor of diminished vagal tone (E/I ratio) and increased sympathetic response to tilt (delta LF/HF-RRI) as measured with HRV. Lower BRS was associated with greater disease severity and older age. Hemodynamic parameters were predominantly predicted by age and sex. Conclusion: Our results confirm cardiac autonomic dysfunction among MG patients with predominant parasympathetic impairment. Clinicians should consider evaluation of autonomic balance in MG patients with, or at risk for, cardiovascular disease.

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Section: Discussionsupporting

confidence: 55%

“…Several studies suggest the presence of complex interactions between disease severity, ANS dysregulation, and chronic inflammation [42]. The imbalance in the ANS may favor inflammation when the SNS is dominant [43,44].…”

Section: Discussionmentioning

confidence: 99%

Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability

Zawadka‐Kunikowska

Rzepiński²,

Tafil-Klawe

et al. 2022

JCM

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“…The mammalian nervous and immune systems evolved to maintain homeostasis and protect the host against tissue injury and infection ( 13 ). Autonomic nerves monitor infection and inflammation and form homeostatic reflexes to regulate host responses ( 14 , 15 ). An important neural conduit for monitoring and regulating immune responses is the vagus nerve (VN), the body's longest cranial nerve.…”

Section: Role Of the Nervous System In Immune And Respiratory Controlmentioning

confidence: 99%

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients

Czura¹,

Bikson

Charvet

et al. 2022

Front. Neurol.

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Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state (“cytokine storm”) observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.

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“…Besides the standard treatment of SSc, which aims to control the inflammatory status and disease progression, other type of treatment should be considered. For future directions pharmacological and non-pharmacological approaches that stimulate the vagus nerve activity could be employed to reduce inflammation via the anti-inflammatory cholinergic reflex (38,39).…”

Section: Clinical Applications and Future Directionsmentioning

confidence: 99%

The Systolic Pulmonary Arterial Pressure Liaises Impaired Cardiac Autonomic Control to Pro-inflammatory Status in Systemic Sclerosis Patients

Rodrigues

Vicenzi

Bellocchi

et al. 2022

Front. Cardiovasc. Med.

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The current study was undertaken to test the hypothesis that systemic sclerosis (SSc) patients with higher systolic pulmonary arterial pressures (PAPs) present a blunted cardiac autonomic modulation and a pro-inflammatory profile. Thirty-nine SSc patients were enrolled (mean age 57 ± 11 years). ECG and respiration were recorded in the supine (SUP) position and during the active standing (ORT). Heart rate variability (HRV) analysis was performed on samples of 300 beats. The symbolic analysis identified three patterns, 0V%, (sympathetic) and 2UV% and 2LV%, (vagal). The %ΔORT was calculated from the differences between HRV in ORT and SUP, normalized (%) by the HRV values at rest. The PAPs was obtained non-invasively through echocardiography. For the inter-group analysis, participants were allocated in groups with higher (+PAPs ≥ median) and lower PAPs (–PAPs < median) values. At rest, the cardiac sympathetic modulation (represented by 0V%) was positively correlated with PAPs, while parasympathetic modulation (represented by 2LV%) was negatively correlated with PAPs. The dynamic response to ORT (represented by Δ0V% and Δ2LV%), sympathetic and parasympathetic were negatively and positively correlated with PAPs, respectively. The +PAPs group presented a higher inflammatory status and a blunted cardiac autonomic response to ORT (↓Δ0V% and ↑Δ2LV%) compared to the –PAPs group. These findings suggest an interplay among cardiac autonomic control, inflammatory status, and cardiopulmonary mechanics that should be considered for the assessment, monitoring, and treatment of SSc patients.

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The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases

Cited by 46 publications

References 162 publications

Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability

Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients

The Systolic Pulmonary Arterial Pressure Liaises Impaired Cardiac Autonomic Control to Pro-inflammatory Status in Systemic Sclerosis Patients

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