The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.

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Objective. To investigate the interplay between active standing and heat stress on cardiovascular autonomic modulation in healthy individuals. Approach. Blood pressure (BP) and ECG were continuously recorded during 30 min in supine (SUP) and 6 min in orthostatic position (ORT) under thermal reference (TC; ∼24 °C) or heated environment (HOT; ∼36 °C) conditions, in a randomized order. All data collection was performed during the winter and spring seasons when typical outdoor temperatures are ∼23 °C. Spectral analysis was employed by the autoregressive model of R–R and systolic blood pressure (SBP) time series and defined, within each band, in low (LF, 0.04 to 0.15 Hz) and high (0.15–0.40 Hz) frequencies. The indices of cardiac sympathetic (LF) and cardiac parasympathetic (HF) were normalized (nu) dividing each band power by the total power subtracted the very-low component (<0.04 Hz), obtaining the cardiac autonomic balance (LF/HF) modulation. The gain of the relationship between SBP and R–R variabilities within the LF band was utilized for analysis of spontaneous baroreflex sensitivity (alpha index; αLF). Nonlinear analysis was employed through symbolic dynamics of R–R, which provided the percentage of sequences of three heart periods without changes in R–R interval (0V%; cardiac sympathetic modulation) and two significant variations (2UV% and 2LV%; cardiac vagal modulation). Main results. HOT increased 0V% and HR, and decreased αLF and 2UV% during SUP compared to TC. During ORT, HOT provokes a greater increment on HR, LF/HF and 0V%, indexes compared to ORT under TC. Significance. At rest, heat stress influences both autonomic branches, increasing sympathetic and decreasing vagal modulation and spontaneous baroreflex sensitivity. The augmented HR during active standing under heat stress seems to be mediated by a greater increment in cardiac sympathetic modulation, showing an interplay between gravitational and thermal stimulus.

Recently, case series studies on patients with SARS-CoV-2 infection reported an association between remdesivir (RDV) administration and incidental bradycardia. However, the phenomenon has not yet been described in detail. We conducted a retrospective case–control study to evaluate the occurrence of RDV‐related bradycardia in patients hospitalized for SARS-CoV2 pneumoniae. We retrospectively evaluated 71 patients, hospitalized in six internal medicine wards of the Milan area, affected by mild-to-moderate COVID-19 who received RDV (RDV group) and 54 controls, matched for sex, age and disease severity on admission (CTR group). The mean heart rate value recorded during the first two days of hospitalization was considered as baseline heart rate (HRb). Heart rate values relative to the 5-days treatment and the 5-days post-treatment were extracted for RDV group, while heart rate values relative to 10 days of hospitalization were considered for the CTR group. ΔHR values were calculated as maximum HR drop versus HRb. Possible associations between ΔHR and clinical-demographic factors were assessed through regression analysis. The RDV group experienced a significantly higher incidence of bradycardia compared to the CTR group (56% vs 33%, OR 2.6, 95% CI 1.2–5.4, p value = 0.011). Moreover, the RDV group showed higher ΔHR values than the CTR group. The HR progressively decreased with daily administration of RDV, reaching the maximun drop on day six (–8.6±1.9 bpm). In RDV group, patients who experienced bradycardia had higher drop in HR, higher alanine aminotransferase (ALT) values at the baseline (bALT) and during the RDV administration period. ΔHR was positively associated with HRb ( β = 0.772, p < 0.001) and bALT ( β = 0.245, p = 0.005). In conclusion, our results confirmed a significant association between RDV administration and development of bradycardia. This effect was proportional to baseline HR and was associated with higher levels of baseline ALT, suggesting a possible interaction between RDV liver metabolism and a vagally-mediated effect on HR due to increased availability of RDV metabolites.

Ischemic stroke is a worldwide major cause of mortality and disability and has high costs in terms of health-related quality of life and expectancy as well as of social healthcare resources. In recent years, starting from the bidirectional relationship between autonomic nervous system (ANS) dysfunction and acute ischemic stroke (AIS), researchers have identified prognostic factors for risk stratification, prognosis of mid-term outcomes and response to recanalization therapy. In particular, the evaluation of the ANS function through the analysis of heart rate variability (HRV) appears to be a promising non-invasive and reliable tool for the management of patients with AIS. Furthermore, preclinical molecular studies on the pathophysiological mechanisms underlying the onset and progression of stroke damage have shown an extensive overlap with the activity of the vagus nerve. Evidence from the application of vagus nerve stimulation (VNS) on animal models of AIS and on patients with chronic ischemic stroke has highlighted the surprising therapeutic possibilities of neuromodulation. Preclinical molecular studies highlighted that the neuroprotective action of VNS results from anti-inflammatory, antioxidant and antiapoptotic mechanisms mediated by α7 nicotinic acetylcholine receptor. Given the proven safety of non-invasive VNS in the subacute phase, the ease of its use and its possible beneficial effect in hemorrhagic stroke as well, human studies with transcutaneous VNS should be less challenging than protocols that involve invasive VNS and could be the proof of concept that neuromodulation represents the very first therapeutic approach in the ultra-early management of stroke.

The analysis of the central and the autonomic nervous systems (CNS, ANS) activities during general anesthesia (GA) provides fundamental information for the study of neural processes that support alterations of the consciousness level. In the present pilot study, we analyzed EEG signals and the heart rate (HR) variability (HRV) in a sample of 11 patients undergoing spinal surgery to investigate their CNS and ANS activities during GA obtained with propofol administration. Data were analyzed during different stages of GA: baseline, the first period of anesthetic induction, the period before the loss of consciousness, the first period after propofol discontinuation, and the period before the recovery of consciousness (ROC). In EEG spectral analysis, we found a decrease in posterior alpha and beta power in all cortical areas observed, except the occipital ones, and an increase in delta power, mainly during the induction phase. In EEG connectivity analysis, we found a significant increase of local efficiency index in alpha and delta bands between baseline and loss of consciousness as well as between baseline and ROC in delta band only and a significant reduction of the characteristic path length in alpha band between the baseline and ROC. Moreover, connectivity results showed that in the alpha band there was mainly a progressive increase in the number and in the strength of incoming connections in the frontal region, while in the beta band the parietal region showed mainly a significant increase in the number and in the strength of outcoming connections values. The HRV analysis showed that the induction of anesthesia with propofol was associated with a progressive decrease in complexity and a consequent increase in the regularity indexes and that the anesthetic procedure determined bradycardia which was accompanied by an increase in cardiac sympathetic modulation and a decrease in cardiac parasympathetic modulation during the induction. Overall, the results of this pilot study showed as propofol-induced anesthesia caused modifications on EEG signal, leading to a “rebalance” between long and short-range cortical connections, and had a direct effect on the cardiac system. Our data suggest interesting perspectives for the interactions between the central and autonomic nervous systems for the modulation of the consciousness level.

Declines in physical performance and cognition are commonly observed in older adults. The geroscience paradigm posits that a set of processes and pathways shared among age-associated conditions may also serve as a molecular explanation for the complex pathophysiology of physical frailty, sarcopenia, and cognitive decline. Mitochondrial dysfunction, inflammation, metabolic alterations, declines in cellular stemness, and altered intracellular signaling have been observed in muscle aging. Neurological factors have also been included among the determinants of sarcopenia. Neuromuscular junctions (NMJs) are synapses bridging nervous and skeletal muscle systems with a relevant role in age-related musculoskeletal derangement. Patterns of circulating metabolic and neurotrophic factors have been associated with physical frailty and sarcopenia. These factors are mostly related to disarrangements in protein-to-energy conversion as well as reduced calorie and protein intake to sustain muscle mass. A link between sarcopenia and cognitive decline in older adults has also been described with a possible role for muscle-derived mediators (i.e., myokines) in mediating muscle–brain crosstalk. Herein, we discuss the main molecular mechanisms and factors involved in the muscle–brain axis and their possible implication in cognitive decline in older adults. An overview of current behavioral strategies that allegedly act on the muscle–brain axis is also provided.