Search Results (54)

Background/Objectives: The management of ventricular arrhythmias (VAs) within cardiac intensive care units (CICUs) is undergoing a significant transformation. This review aims to analyze the historical transition from a narrow focus on arrhythmia-specific treatments toward on the multidisciplinary heart rhythm team. Methods: A narrative revies was conducted. Results: Effective management of electrical storm (ES) requires prompt attenuation of sympathetic hyperactivity, with a preference for non-selective beta-blockers and the implementation of deep sedation. The use of mechanical circulatory support (MCS) has emerged as a mechanical antiarrhythmic strategy by facilitating ventricular unloading and reducing myocardial wall stress. Furthermore, early catheter ablation, guided by 3D electroanatomical mapping and advanced imaging, has proven superior to salvage procedures for stabilizing the arrhythmic substrate. Finally, the integration of palliative care ensures ethical stewardship during refractory shock. Conclusions: Modern VAs management in the CICUs represents a convergence of technology, biology, and multidisciplinary coordination. Full article

Hypertension is the leading global risk factor for cardiovascular diseases, and its pathogenesis is closely linked to excessive sympathetic activation, which markedly elevates the risk of stroke, heart failure and other adverse cardiovascular events. Traditional therapies mainly target peripheral mechanisms, whereas the clinical efficacy of renal denervation highlights the critical role of central regulation in sympathetic hyperactivity. This review focuses on the core sympathetic nuclei including the rostral ventrolateral medulla (RVLM) and paraventricular nucleus (PVN), with epigenetic regulation as a key innovative perspective. We systematically summarize the upstream driving effects of reactive oxygen species (ROS) and neuroinflammation, and emphasize lncRNA/miRNA-mediated post-transcriptional regulation and the modulatory actions of gasotransmitters. Under stress conditions, aberrant activation of ROS and neuroimmune pathways, epigenetic reprogramming, and hyperexcitability of central sympathetic neurons act as key events in sympathetic overactivation, which interact synergistically to promote hypertension. Integrating evidence from multiple hypertensive animal models and clinical studies, we discuss multimodal interventions including pharmacotherapy, nanozyme biotechnology and neuromodulation, analyze current translational challenges, and provide a theoretical framework for developing central-targeted antihypertensive therapies. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID-19 syndrome share a symptom profile, including severe fatigue, cognitive dysfunction, exertional intolerance, sleep disturbances, hypervigilance, and the paradoxical state of being “wired but tired.” A well-established finding is sympathetic hyperactivity with reduced vagal tone, typically interpreted as autonomic nervous system dysfunction. Emerging evidence, however, suggests a broader disturbance across multiple neurotransmitter systems. This paper reviews current knowledge on neurotransmitter systems implicated in ME/CFS and Long COVID, focusing on potential mechanisms of dysregulation and their roles in disease pathology and symptom generation, as well as implications for treatment. In addition to abnormalities of the noradrenergic system, disturbances in serotonergic, GABAergic, and glutamatergic signaling have been reported. Contributing factors may include autoimmunity, neuroinflammation, gut dysbiosis, epigenetic influences, and stressors such as orthostatic intolerance, metabolic strain, and pain. A shift favoring excitatory over inhibitory neurotransmission can lead to excessive neural activation, autonomic dysfunction, sensory hypersensitivities, sleep disturbances, and cognitive impairment. Reduced GABAergic tone combined with increased glutamatergic and noradrenergic activity may elevate skeletal muscle tone, contributing to calcium overload, mitochondrial dysfunction, exertional intolerance, and post-exertional malaise. Various pharmacological treatments may partially rebalance these neurotransmitter systems, but limited efficacy highlights the need for systematic investigation and individualized strategies. Full article

Excessive activation of the sympathetic nervous system is a prominent contributor linked to heart failure (HF) progression. Pathological remodeling of the central nervous system represents a plausible upstream event associated with central sympathetic hyperactivity, whereas dysfunction of the brain–heart axis may act as a pivotal hub involved in this pathological process. This review systematically summarizes the functional characteristics of major sympathetic regulatory nuclei under HF, including the subfornical organ (SFO), paraventricular nucleus of the hypothalamus (PVN), rostral ventrolateral medulla (RVLM), and nucleus tractus solitarius (NTS). Following the pathological logic from upstream initiation to inter-organ closed-loop responses, seven interconnected pathological mechanisms are analyzed: glial cell activation and neuroinflammation, endoplasmic reticulum stress, renin–angiotensin system (RAS) imbalance, abnormal signaling pathways and transcription factors, impaired neuronal microenvironment homeostasis, dysregulated post-transcriptional and post-translational modifications, and extracellular vesicle-mediated inter-organ signal transmission. Their cross-regulation and positive feedback amplification effects are highlighted. Multidimensional central-targeted intervention strategies established on this basis possess important fundamental significance and translational potential. This review also discusses current scientific challenges and prospects for interdisciplinary frontiers, providing theoretical references and practical insights for central regulation research in HF and its precise clinical translation. Full article

Iron deficiency (ID) is frequent in patients with heart failure (HF) and is correlated with adverse outcomes, yet its involvement in HF pathophysiology is not fully understood. Hyperactivity of the sympathetic nervous system (SNS) is the central feature of HF. We aimed to compare the effects of isoproterenol (ISO), a β-adrenergic agonist (SNS stimulation), with those of the iron chelator deferoxamine (DEF), to evaluate how β-adrenergic stimulation influences cardiac iron. In this study, H9c2 cardiac cells were challenged with ISO, DEF or both and several parameters related to iron metabolism were analyzed. In all cases, the cells decreased their intracellular iron levels. ISO induced alterations in key cardiac iron metabolism molecules that were, in most cases, comparable to those elicited by DEF, emphasizing the direct impact of β-adrenergic stimuli on iron metabolism and mitochondrial dysfunction. Nevertheless, unlike DEF, ISO triggered a shift in mitochondrial energy metabolism. These findings suggest that β-adrenergic stimulation, as a major component of neurohormonal activation, may contribute to the development of ID in cardiac cells, highlighting the importance of iron homeostasis and the need to further investigate iron dysregulation in this context. Full article

Hypertension-induced renal injury is a major cause of chronic kidney disease and end-stage renal disease. Increasing evidence indicates that disease progression is not driven solely by hemodynamic stress but results from the interplay of multiple molecular mechanisms. In this review, we propose a stage-structured and network-based framework to systematically integrate current mechanistic insights into hypertension-induced renal injury. Early events, mainly including endothelial dysfunction and renal hypoxia, establish a permissive microenvironment for disease progression. These insults activate amplifying pathways such as the renin–angiotensin–aldosterone system (RAAS) overactivation, oxidative stress, immune and inflammatory responses, and sympathetic nervous system hyperactivity, which interact through cross-talk and positive feedback loops. Ultimately, these signals converge on fibrotic programs characterized by epithelial–mesenchymal transition (EMT), fibroblast activation, and extracellular matrix deposition, leading to irreversible structural remodeling and functional decline. Furthermore, epigenetics, the gut–kidney axis, autophagy dysfunction and renal aging also contribute to this process. We highlight two critical and underappreciated aspects: the existence of a permissive ‘early-window’ dominated by endothelial dysfunction and hypoxia, which sets the stage for later amplification; and the hierarchical interplay between amplifying mechanisms where cross talk creates self-reinforcing loops that may explain therapeutic resistance. In addition, this review highlights emerging biomarkers for early diagnosis and disease monitoring, and discusses therapeutic advances that extend beyond blood pressure control to disease-modifying interventions that confer renoprotective effects. By integrating molecular mechanisms with diagnostic and therapeutic perspectives, this review provides a comprehensive framework for early detection and precision intervention in hypertension-induced renal injury. Full article

Background and Objectives: The combination of resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) accelerates the development of chronic kidney disease (CKD), which may be largely associated with sympathetic hyperactivity. Distal renal denervation (dRDN) effectively reduces sympathetic flow to the kidneys, causing renal vasodilation and increased renal perfusion. However, this effect may be limited by nephrotoxicity due to the multiple increase in the number of contrast injections, as well as a significant blood pressure (BP) reduction, which naturally worsens renal perfusion. This study aimed to test the hypothesis that dRDN prevents the progressive decline in kidney function in patients with RHTN and T2DM. Materials and Methods: The prospective interventional study (REFRAIN, NCT04948918) included men and women > 20 y.o. with true RHTN. Eligible patients underwent dRDN. The primary endpoint was a change in eGFR from baseline to 12 months. Secondary endpoints were changes in 24 h BP, serum lipocalin-2, cystatin C, 24 h urinary albumin excretion, renal blood flow, and kidney volumes (by MRI). Multiple regression analysis was used to find independent predictors of individual estimated glomerular filtration rate (eGFR) change. Results: A total of 29 patients with RHTN and T2DM were included in the study (61.6 ± 7.2 y.o., 10 males, mean 24 h ambulatory BP: 158.1 ± 21.4/81.8 ± 12.4 mmHg (systolic/diastolic, respectively)), HbA1c: 7.8 ± 1.4%, and eGFR 56.7 ± 19.9 mL/min/1.73 m², 23 (79%) patients with CKD, and 2 patients with albuminuria only. There were no perioperative complications. Twenty-seven (93%) participants completed 12 month follow-up. eGFR did not change from baseline: +1.3 mL/min/1.73 m² [95% CI: −9.6, 12.1], despite the expected decrease due to a significant decrease in 24 h systolic BP (−18.2 mmHg [95% CI: −28.6, −7.8]). No changes in other secondary endpoints were observed. Independent predictors of individual eGFR change were baseline 24 h pulse pressure (p = 0.030) and HbA1c (p = 0.010). Conclusions: Distal RDN demonstrates a substantial nephroprotective effect in patients with RHTN and T2DM, which may be partly mediated by a reduction in arterial stiffness and is negatively dependent on baseline hyperglycemia. Full article

Patients with multiple traumas, particularly those with traumatic brain injury (TBI), are among the most challenging cases in intensive care medicine. Although early orotracheal intubation and invasive mechanical ventilation (IMV) are essential for airway protection and neurological treatment, they significantly increase the risk of lower respiratory tract infection (LRTI), including ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). These complications are particularly prevalent among neurocritical patients due to the distinctive interaction between the brain, lungs and immune system. This narrative review examines the current evidence on the mechanisms underlying the brain–lung–immune axis; the diagnostic challenges in identifying respiratory infections in mechanically ventilated TBI patients; and optimal approaches to empirical or quasi-targeted antimicrobial therapy based on diagnostic algorithms and rapid molecular techniques. Severe TBI induces neurogenic inflammation, autonomic dysregulation, and immunosuppression, thereby increasing susceptibility to pulmonary infections. The ‘triple hit hypothesis’ best explains this cascade: sympathetic hyperactivity (first hit), iatrogenic ventilatory injury (second hit), and intestinal dysbiosis with systemic immune dysregulation (third hit). VAP diagnosis remains challenging due to the lack of universal criteria, the overlap with systemic inflammatory response syndrome, and the low specificity of radiological and clinical signs. VAT may represent an intermediate stage within a continuum of ventilator-associated infection. Recent evidence supports the selective use of nebulized antibiotics for VAT, advocating an individualized, locally adapted empirical approach to VAP treatment. Syndromic molecular panels can accelerate the identification of pathogens, enabling the earlier and more appropriate selection of antimicrobials and improving outcomes while preserving stewardship. Understanding the brain–lung–immune axis and improving diagnostic accuracy are essential to enhancing the treatment of respiratory infections in neurocritical care. Integrating clinical assessment, biomarkers and rapid microbiological testing enables timely, targeted therapy and reduces the misuse of antimicrobials. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Evidence has suggested that post-exercise heart rate recovery (PHRR) is a useful tool in evaluating cardiac autonomic function. Altered cardiac autonomic function is characterized by heightened sympathetic activation and the abnormal reactivation of the parasympathetic nervous system and is associated with delayed HRR. Although grape seed extract (GSE) supplementation has been shown to increase nitric oxide production and modify sympathetic output, there is limited evidence on its potential beneficial effects on PHRR. We investigated the effect of GSE supplementation on PHRR during sympathetic overactivation induced by muscle metaboreflex activation (MMA) in young individuals. Participants were randomly assigned, via a double-blind, cross-over design, to either receive GSE (300 mg, two capsules) or PL (300 mg, two capsules), with a washout period of at least 72 h. between trials. A submaximal exercise test was performed using a cycle ergometer combined with an isometric handgrip exercise using a handgrip dynamometer and blood flow occlusion by placing a cuff over the brachial artery of the dominant arm. PHRR was measured at 5 s. intervals throughout the experiment. The PHRR was evaluated between GSE and PL at every min. for 300 s. PHRR kinetics significantly improved following GSE supplementation (74.3 ± 7.5 s) compared with the PL condition (86.2 ± 10.4 s). Our results suggest that GSE is effective in improving HRR kinetics during heightened sympathetic activity induced by MMA in young individuals (p = 0.034; ES = 0.4). Thus, regular treatment with GSE may provide a nonpharmacological intervention to reduce sympathetic hyperactivity in conditions where excessive sympathetic activity is consistently present. Full article

Cockpit noise, as a critical environmental factor affecting flight safety, may impair pilots’ cognitive functions, leading to a decreased operational performance and decision-making errors, thereby posing potential threats to aviation safety. In order to reveal the relationship between the cockpit noise sound pressure level and pilot physiological indicators, and provide a scientific basis for cockpit noise airworthiness standards, this experiment takes pilot trainees as the research subject. Based on the principle of multimodal data synchronization, a sound field reconstruction system is used to reconstruct the cockpit sound field. Electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal activity (EDA) measurements are carried out in different sound pressure level noise operating environments. The results show that with the increase in the sound pressure level, the significant suppression of α-wave activity in the occipital and parietal regions suggests that the cortical resting state is lifted and visual attention is enhanced; the enhancement of the β-wave in the frontal regions reflects the enhancement of alertness and prefrontal executive control, and the suppression of θ-wave activity in the frontal and temporal regions may indicate that cognitive tuning is suppressed, which reflects the brain’s rapid adaptive response to external noise stimuli in a high-noise environment; noise exposure triggers sustained sympathetic nerve hyperactivity, which is manifested by a significant acceleration of the heart rate and a significant increase in the mean value of skin conductance when the noise sound pressure level exceeds 70 dB(A). The correlation analysis between physiological indicators shows that cockpit noise has a multi-system synergistic effect on human physiological indicators. The experimental results indicate that noise has a significant impact on EEG, ECG, and EDA indicators. Full article

Background: Stellate Ganglion Blocks (SGB) involve injecting local anesthetic near the stellate ganglion, which includes the C6, C7, and T1 ganglia. This procedure induces a sympathetic blockade and has been employed to address various conditions, such as post-traumatic stress disorder (PTSD), ventricular arrhythmias, and chronic pain syndromes like complex regional pain syndrome (CRPS). Central to this case series is the exploration of SGB as a unified treatment for PTSD and chronic low back pain—two conditions linked by central sensitization. Case Series Overview: The study presents three female veterans with histories of PTSD, chronic low back pain, and myofascial pain. These patients had not responded to conventional treatments, including medications and interventional procedures. They underwent SGB with a combination of 10 mg preservative-free dexamethasone sodium phosphate, 4 mL preservative-free lidocaine 2% with epinephrine, and 1 mL preservative-free bupivacaine 0.25%. The procedure was well tolerated without adverse effects. All three patients experienced significant improvements. The first and third patients reported reductions in PTSD symptoms, low back pain, and myofascial pain. The second patient experienced relief from PTSD symptoms and prolonged reduction in myofascial pain. This case series is the first to document SGB’s effectiveness in treating chronic low back pain alongside PTSD. Conclusions: The findings suggest that SGB could be an effective therapy for chronic overlapping conditions like PTSD, chronic low back pain, and myofascial pain, all of which share central sensitization mechanisms. The literature supports the notion that these conditions involve both physical and psychiatric components potentially responsive to SGB. By targeting sympathetic hyperactivity and reducing norepinephrine levels, SGB may alleviate symptoms across these interconnected syndromes. This case series highlights the potential of SGB as a novel approach for managing comorbid PTSD and chronic pain conditions. Further research is warranted to confirm its efficacy and explore its broader applications in treating central sensitization-related disorders and chronic overlapping pain conditions (COPC), potentially responsive to sympathetic blockade. Full article

Obesity is a multifactorial condition linked to severe health complications, including cardiovascular diseases and endothelial dysfunction. Both obesity and high-fat diets (HFDs) are strongly associated with neuroinflammation, particularly in the hypothalamus. The autonomic nervous system (ANS), which controls involuntary physiological processes, is critical for maintaining cardiovascular health, and its dysfunction is implicated in endothelial disorders. With its homeostatic control centers located in the hypothalamus and brainstem, a crucial question arises: could obesity- and HFD-induced neuroinflammation disrupt central ANS structures, leading to ANS dysfunction and subsequent endothelial disorders? This review examined whether neuroinflammation caused by obesity and HFD contributes to endothelial dysfunction through the dysregulation of the ANS. Our analysis revealed that hypothalamic inflammation linked to obesity and an HFD is associated with sympathetic hyperactivity and endothelial disorders. Identified molecular mechanisms include the influence of inflammatory cytokines, activation of the NF-κB/IKK-β pathway, microglial activation mediated by angiotensin II, circulating mitochondria triggering cGAS activation, and the stimulation of the TLR4 pathway. Our findings suggest that hypothalamic inflammation may play a central role in the interplay between obesity/an HFD, ANS dysfunction, and endothelial disorders. Full article

Agitation is a common and difficult-to-manage neuropsychiatric syndrome in dementia. Recently, an association with the autonomous nervous system has been suggested. From the literature researched, however, only two studies investigating autonomic function concomitant to agitation situations appeared; one case series comprised two American veterans with vascular and Alzheimer’s dementia, respectively, and in a case series of patients with CLN3 (juvenile neuronal ceroid lipofuscinosis), this was found to be the most common neurodegenerative disease leading to dementia in childhood. In both case series, the measurement of the autonomic system disclosed a parasympathetic withdrawal and sympathetic hyperactivity in the temporal context with agitated behavior. If the time-wise-related autonomic imbalance shown previously can be demonstrated in a larger cohort of patients with Alzheimer’s disease, the use of transcutaneous vagal stimulation might be a potential paradigm shift in the treatment of agitation in Alzheimer’s disease. Full article

Drug-induced gingival overgrowth is associated with various systemic diseases, including epilepsy. Among antiepileptic medications, phenytoin is commonly reported to cause this condition. In contrast, sodium valproate (VPA), another widely used antiepileptic drug, rarely induces gingival overgrowth. This difference in side effects highlights the variability in drug-induced oral complications among different antiepileptic medications. This case study presents a patient who developed significant gingival overgrowth after using VPA for over 10 years. The study aims to identify VPA as the causative agent and observe changes during long-term administration and after dose reduction. Our findings demonstrate that even long-standing gingival overgrowth can improve rapidly following discontinuation of the causative medication, providing valuable insights for managing similar cases in the future. Full article