Search Results (106)

Obstructive sleep apnea (OSA) constitutes a chronic disorder characterized by recurrent upper airway collapse during sleep. This condition is prevalent among patients with cardiac rhythm disturbances and represents a potent independent risk factor for arrhythmia. Although most studies have concentrated on the association between OSA and atrial fibrillation (AF), numerous investigations have established connections with ventricular and supraventricular arrhythmias. Arrhythmogenesis in OSA represents a complex multifactorial phenomenon. Acute mechanisms involve induction of negative intrathoracic pressure during the effort to breathe, which triggers recurrent episodes of hypoxia, hypercapnia, alterations in carbon dioxide and acid–base equilibrium, as well as surges in sympathetic nervous system activity. Chronic intermittent hypoxia (CIH) and negative thoracic pressure (NTP) induce atrial stretch, chronic structural remodeling, and elevated vagal tone, thereby heightening susceptibility to bradycardic and conduction arrhythmias. Intermediate pathways through which OSA may precipitate arrhythmia encompass heightened systemic inflammation, oxidative stress, a prothrombotic state, and vascular dysfunction. Long-term OSA is linked with atrial enlargement and fibrosis, ventricular hypertrophy, hypertension, and coronary artery disease. These factors predispose to cardiac arrhythmias through the following mechanisms: shortening of the atrial effective refractory period, abnormal automaticity, promotion of slowed and heterogeneous conduction, enhancement of reentrant arrhythmia persistence, and prolongation of the QT interval. In this paper, we aim to present the pathophysiological mechanisms underpinning the association between obstructive sleep apnea and cardiac arrhythmias. Understanding the precise pathophysiological pathways by which obstructive sleep apnea contributes to arrhythmogenesis will enable targeted preventive stratification of patients at risk for cardiovascular events and promote the development of innovative therapies to attenuate OSA-induced arrhythmogenicity. Full article

Driving with assistive devices creates complex cognitive and emotional demands that require systematic investigation. This study uses a multivariate approach based on subjective and objective measures to evaluate mental workload (MWL), stress and emotional state during simulated driving with an assistive device. Thirty healthy adults ($42\pm 13$ years of age, 7 females) completed four driving tasks combining two levels of difficulty (Easy vs. Hard) and two steering tools (wheel vs. single-pin aid). Subjective measures from NASA Task Load Index and Self-Assessment Manikin were collected, as well as physiological parameters from electroencephalographic, electrocardiographic, and electrodermal activity signals. The results revealed that the assistive device significantly induced increases in perceived physical demand, frustration, loss of emotional control and stress, yet reducing intrinsic sympathetic response represented by electrodermal activity parameters. Multivariate analyses highlighted that combining different physiological predictors improved MWL estimation. This study marks an initial step towards understanding the impact of assistive devices on MWL and stress in post-acute individuals returning to driving. Full article

Aerobic exercise capacity, best quantified by maximal oxygen uptake (VO_2max), varies between individuals and is dependent on cardiac output (CO) and oxygen uptake in the periphery (a-vO₂ diff). Environmental stressors like hypoxia, microgravity, and heat negatively impact these parameters, thereby reducing aerobic exercise capacity. However, in response to acute and chronic exposures to these environments, compensatory processes serve to counteract reductions in VO_2max. In hypoxic environments, reduced oxygen partial pressure (PO₂) leads to hypoxic pulmonary vasoconstriction (HPV) and a diffusion limitation at the level of the lungs and skeletal muscle, resulting in a reduction in VO_2max. Microgravity environments reduce VO_2max through cardiac and skeletal muscle deconditioning, as well as reductions in plasma volume (PV), resulting in an increase in sympathetic nerve activity through baroreceptor-mediated pathways. In heat stress environments, increases in skin perfusion upon acute exposure hinder exercise performance, whereas compensatory PV expansion mitigates further decreases in VO_2max. As humans are increasingly exposed to austere environments and environmental extremes, it is critical to understand how these environments impact cardiovascular exercise physiology so that effective strategies and protocols ensuring proper aerobic functioning may be implemented. Full article

A male castrated Shih Tzu was evaluated for recurrent nocturnal episodes of acute respiratory distress accompanied by hemoptysis and transient erythrocytosis. The dog was clinically normal between episodes, but each nighttime event was severe and prompted repeated emergency visits. During each emergency presentation, thoracic radiographs revealed severe diffuse interstitial-to-alveolar pulmonary infiltrates, and packed cell volume showed marked but reversible increases. A stepwise diagnostic evaluation, including serial indirect blood pressure measurement, coagulation assessment, echocardiography, and bronchoscopy with bronchoalveolar lavage, progressively excluded typical infectious, cardiac, structural, and coagulopathic causes of hemoptysis and acute respiratory distress. Given the stereotyped pattern of near-acute crises with diffuse pulmonary infiltrates and hemoptysis, mechanisms analogous to noncardiogenic pulmonary edema or exercise-induced pulmonary hemorrhage were considered. Therapeutic trials with sildenafil and furosemide failed to prevent further nocturnal recurrences. Considering concurrent transient PCV surges and the proposed role of catecholamine-driven splenic contraction as a rapidly mobilizable erythrocyte reservoir, a sympathetically mediated process was suspected, and α₁-adrenergic blockade with prazosin was initiated. Following prazosin therapy, sustained clinical remission was achieved, with no further emergency episodes over a 17.5-month follow-up period. The response may have reflected multiple pharmacological effects of prazosin, including attenuation of sympathetically mediated splenic α₁-adrenergic activity, systemic vasodilation, and reduction in venous return. This unique case suggests that dysregulation of the sympathetic nervous system may have contributed to the recurrent hemoptysis and acute respiratory distress and highlights adrenergic modulation as a potential therapeutic consideration in similar cases. Full article

The impact of anesthetic technique on long-term oncologic outcomes remains controversial. While early observational data suggested that regional anesthesia might reduce cancer recurrence, large randomized trials have failed to demonstrate consistent survival benefits. This apparent contradiction may not reflect biological neutrality, but rather a mismatch between trial design and the inflammatory biology of the perioperative period. Surgical resection provokes an acute and intense inflammatory surge characterized by sympathetic activation, cytokine release, neutrophil extracellular trap formation, endothelial activation, and transient suppression of cellular immunity. During this perioperative inflammatory window, circulating tumor cells encounter a biologically permissive microenvironment that may facilitate immune evasion, adhesion, and early metastatic niche establishment. The magnitude of this inflammatory response varies across patients and may represent a critical, yet under-recognized, determinant of tumor–host dynamics. Anesthetic and analgesic strategies influence this inflammatory cascade. By attenuating nociceptive signaling and sympathetic activation, regional anesthesia may modulate perioperative immune and immunometabolic pathways. However, it should not be framed as an anti-cancer therapy per se, but rather as a potential regulator of the transient inflammatory milieu that shapes early oncologic biology. We propose that prior neutral trials may reflect methodological misalignment, including heterogeneous tumor populations, absence of inflammatory stratification, and reliance on distant survival endpoints without mechanistic correlates. Future investigations should integrate perioperative immune phenotyping, inflammatory biomarkers, and tumor subtype stratification to determine whether modulation of acute surgical inflammation meaningfully alters early tumor–host interactions. Reconceptualizing the perioperative period as a biologically active inflammatory interface may refine the anesthesiologist’s role within perioperative oncology and open new avenues for precision-based perioperative modulation. Full article

Research suggests fear of sleep (FoS) may be an important consequence of trauma that increases risk for posttraumatic stress disorder (PTSD), especially among patients experiencing ongoing threat after their trauma has ended. Community violence exposure may reinforce perceptions of threat, compounding the pathogenic effect of FoS after trauma. The current study investigated whether FoS increases within the acute aftermath of trauma, and if such increases in FoS predict future PTSD severity. Further, we tested whether community violence exposure moderates the prospective relationship between FoS and PTSD. We recruited patients from an urban Level I trauma center (N = 88; M_age = 39.53 ± SD 14.31, 67.0% male, 67.0% Black). Patients reported FoS within one week of trauma (T1) and again one month later (T2), and PTSD symptoms two months later (T3). We operationalized community violence exposure as the frequency of hearing gunshots in the 90 days prior to trauma. FoS significantly increased from T1 (M = 8.80) to T2 (M = 11.98), p = 0.015, g = 0.28. Change in FoS significantly predicted PTSD symptoms at T3, and this effect was most pronounced among patients who frequently heard gunshots in their community (β = 0.61, SE = 0.35, p = 0.005). Exploratory analyses in a subsample of patients revealed preliminary associations between skin conductance reactivity and sleep fears at T1, tentatively suggesting heightened sympathetic activation as a corollary of fear of sleep. This study provides novel evidence that FoS increases in response to acute trauma exposure and, in turn, predicts future PTSD severity. Moreover, patients exposed to community violence may be especially vulnerable to these effects, perhaps due in part to continued threats to safety. Acute trauma patients who develop sleep fears may be vulnerable to PTSD, particularly those returning to neighborhoods marked by high levels of community violence. Full article

Skin nerve activity (SKNA), extracted from electrocardiograms, is a noninvasive surrogate of sympathetic nervous system (SNS) activity. We evaluated whether complexity-based metrics derived from integrated SKNA (iSKNA; 500–1000 Hz) and time-varying SKNA (TVSKNA; 160–1140 Hz) discriminate SNS activation in experimental (n = 23) and clinical dental datasets (n = 49). Experimental tasks included the Valsalva maneuver and thermal grill stimulation; clinical recordings involved cold testing, with exploratory subgroup analyses based on anxiety status. Pain intensity was assessed using a visual analog scale (VAS); clinically significant pain (CSP+) was defined as a VAS score ≥ 4. Approximate entropy, sample entropy, Hjorth mobility and complexity, Katz fractal dimension, and standard deviation were computed. In the experimental dataset, the Valsalva maneuver produced large-to-huge effects (Cohen’s d = 1.93–3.46, p < 0.001). Thermal grill tasks showed moderate-to-large effects for adjacent pain levels (|d| = 0.63–0.71). ROC analysis showed strong discrimination for baseline vs. pain (AUC 0.80–0.99) but limited separation between adjacent pain levels (AUC 0.56–0.64). In the clinical dataset, discrimination was strongest for no pain vs. CSP+ (|d| = 0.86–1.17), with higher AUC in severe-anxiety participants (0.81–0.96) than non-severe (0.64–0.75). Complexity measures generally decreased during SNS activation, complementing amplitude-based changes. These findings support combined magnitude- and complexity-based descriptors for characterizing short-term sympathetic activation. Full article

Hypertension (HTN) remains a leading modifiable risk factor for cardiovascular disease, and non-pharmacological strategies combining exercise training with plant-derived bioactive supplementation are increasingly recognized as promising adjuncts for blood pressure (BP) management. This evidence-based review synthesizes findings from 31 clinical studies investigating selected plant-based supplements with the strongest available clinical evidence, namely beetroot juice (BRJ), green tea (GT), curcumin (CN), resveratrol (RSV), and garlic, administered alone or in combination with different exercise modalities across acute, short-term, and long-term interventions. Collectively, the evidence indicates that BRJ exerts the most consistent BP-lowering effects, particularly during aerobic training performed at ~50% heart rate reserve (HRR), or ~60% peak oxygen consumption (VO_2peak) in individuals with early-stage vascular dysfunction. CN and garlic also enhance exercise-induced BP reductions, especially in older or metabolically compromised populations. GT shows variable outcomes depending on caffeine content, exercise modality, and participant health status, while RSV provides modest vascular support, often contingent on concurrent training. Mechanistically, these botanicals and exercise converge on key vascular-regulatory pathways, including enhanced nitric oxide (NO) bioavailability, reduced oxidative stress and inflammation, attenuated renin–angiotensin–aldosterone system (RAAS) and sympathetic activity, and improved mitochondrial function through Sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signaling. Together, these integrated mechanisms improve endothelial function, lower vascular resistance, and ultimately reduce BP. From a translational standpoint, combining exercise with targeted plant-based supplementation offers a safe, accessible, and physiologically synergistic strategy for BP control in clinical populations. Future research should define optimal dosing, timing relative to exercise, and population-specific efficacy to inform precision-based, integrative interventions for HTN management. Full article

Background and Objectives: Monday syndrome refers to a psychosomatic stress response occurring at the beginning of the work week and has been implicated in triggering acute cardiovascular events. This study aimed to evaluate the association between Monday syndrome and the incidence of cardiovascular emergencies. Materials and Methods: Between June 2024 and June 2025, a total of 500 patients aged 18–65 years who presented with acute cardiovascular events at two centers were retrospectively analyzed. Diagnoses included STEMI, NSTEMI, unstable angina, ventricular tachycardia/fibrillation, and hypertensive emergency. The distribution of events by weekday and hour was examined. Poisson regression was used to assess the effect of Mondays on event incidence. Results: Of 500 patients (mean age 49.1 ± 9.7 years, 50.4% male), the most common diagnoses were STEMI (31.8%) and NSTEMI (27.4%). The incidence of cardiovascular events was highest on Mondays (19.6%) and lowest on Sundays (10.6%). The early-morning period (06:00–10:00) showed the most significant clustering of events (p < 0.001). Systolic blood pressure (145 ± 18 vs. 139 ± 17 mmHg, p = 0.008) and heart rate (87 ± 12 vs. 82 ± 13 bpm, p = 0.01) were significantly higher on Mondays. Monday presentation was associated with a 23% higher event rate (incidence rate ratio [IRR] 1.23, 95% CI 1.10–1.38, p = 0.002). Conclusions: Monday syndrome is associated with a significant increase in the incidence of cardiovascular emergencies, especially in the early-morning hours. Increased sympathetic tone, hormonal activation, and psychosocial stress are possible contributors. Full article

Evidence indicates that seminal plasma (SP) has pregnancy-favorable biological effects, but there is no definitive proof that exposure to SP increases pregnancy rates in assisted reproductive techniques. We previously showed that this discrepancy may be due to male stress altering SP composition. This study investigated the association between male stress biomarkers in saliva, serum and SP and key determinants of female fertility in women exposed to their partner’s SP during the intracytoplasmic sperm injection (ICSI) cycle. The prospective pilot study included couples with tubal infertility who had unprotected intercourse during the ICSI cycle, supplemented by intravaginal SP injection on the oocyte retrieval day. Salivary cortisol and seminal noradrenaline were quantified by enzyme-linked immunosorbent assay to assess the activity of the hypothalamic–pituitary–adrenal axis and sympathetic nervous systems. Seminal interleukin-18 was measured using LegendPlex™ technology. Cluster analysis of male stress biomarkers identified two neuroendocrine-immune (NEI) phenotypes, characterized by signs of acute (phenotype-1) and chronic (phenotype-2) stress. Women with NEI phenotype-2 partners had fewer collected, mature, and fertilized oocytes, thinner endometrium, and significantly lower pregnancy rates (18.2%) compared to those with NEI phenotype-1 partners (84.6%). These data may suggest a dual role for SP in female fertility, depending on the type of male stress. Full article

Background: Carbon dioxide (CO₂) is traditionally regarded as a metabolic by-product; however, growing evidence indicates that it plays an active regulatory role across multiple physiological systems. Acute hypercapnia elicits respiratory, cardiovascular, metabolic, immune, and neurocognitive responses, some of which may transiently influence exercise performance. This narrative review summarizes current evidence on CO₂ inhalation in healthy individuals and critically evaluates whether controlled hypercapnia may serve as a targeted stimulus in sport and exercise contexts. Methods: A narrative review of peer-reviewed English-language articles indexed in PubMed and Web of Science was conducted. A narrative approach was chosen due to the marked heterogeneity of study designs, hypercapnia-induction methods (e.g., CO₂ inhalation, voluntary hypoventilation, increased respiratory dead space), participant characteristics, and outcome measures, which precluded systematic synthesis. The review focused on studies involving healthy or physically active individuals and examined acute or short-term hypercapnic exposure. No strict publication date limits were applied. Studies conducted exclusively in clinical populations were excluded. Results: Short-term, controlled hypercapnia reliably increases ventilation, sympathetic activation, cerebral and muscular blood flow, and metabolic stress. Certain hypercapnia-based interventions—such as voluntary hypoventilation or added respiratory dead space—may enhance buffering capacity, reduce lactate accumulation and improve maximal oxygen uptake (VO₂max) during submaximal efforts and repeated-sprint performance during high-intensity, short-duration exercise. However, CO₂ inhalation frequently induces dyspnea, anxiety, and cognitive disruption, and higher concentrations pose clear safety risks. Current evidence does not support long-term improvements in VO₂max or long-duration endurance performance following hypercapnia-based interventions. Conclusions: Controlled, intermittent hypercapnia may provide a targeted metabolic and ventilatory stimulus that enhances tolerance to high-intensity exercise, yet its application remains experimental and context-dependent. The risks associated with CO₂ inhalation in healthy individuals currently outweigh its potential benefits, and safe, effective training protocols have not been fully established. Further research is needed to clarify the mechanisms, long-term adaptations, and practical utility of hypercapnia-based training strategies. Full article

Memory function is susceptible to decline with age, stress, and neurological diseases, highlighting the importance of exploring effective and sustainable strategies to enhance memory consolidation. Epinephrine plays a key role in memory consolidation; acute, moderate elevations enhance memory, while chronic high levels are inhibitory. Given the limitations of pharmacological interventions, this study aims to investigate exercise as a non-pharmacological means to promote post-learning memory consolidation by inducing acute epinephrine release, focusing on its mechanisms and optimized implementation strategies. This narrative review systematically reviews evidence from neurophysiology, molecular biology, and behavioral experiments and finds that exercise can safely and controllably activate the sympathetic–adrenal system, leading to a rapid rise in epinephrine. The release kinetics align highly with the critical time window for memory consolidation. Moderate-intensity aerobic exercise implemented within 30 min post-learning can significantly improve memory retention. The mechanisms involve not only epinephrine enhancing synaptic plasticity and LTP by activating hippocampal β-adrenergic receptors, but also synergistic effects across multiple systems, such as promoting osteocalcin signaling, upregulating BDNF expression, inducing neurogenesis, and optimizing cerebral metabolism and blood flow. Evidence suggests that exercise, as a non-pharmacological intervention, significantly enhances post-learning memory consolidation through the precise modulation of epinephrine release and multi-system synergy, offering both high efficacy and safety. Future research should focus on developing precise exercise prescriptions based on individual characteristics and leveraging wearable devices and digital technologies to improve intervention adherence and applicability, promoting its widespread use in educational and clinical settings. Full article

Cardiorenal syndrome (CRS) is a term that describes the pathological interplay between the heart and kidney wherein either organ may be the originating stimulus that leads to acute and eventually chronic disease in the other. The mechanisms by which either initial disease progression influences the target organ are multifactorial and primarily include inflammation, alternated hemodynamics and blood volume handling, and neurohormonal alterations. The order of initiation of CRS, depending on which target organ the stimulus arises from, likely impacts the overall feed-forward mechanisms of this syndrome’s pathology; however, the end results are similar: accentuated chronic inflammation and heightened autonomic output. The latter of these symptoms of CRS is especially concerning as heightened sympathetic activity enhances the risk of various other cardiovascular events such as stroke and heart attack and ultimately limits non-pharmacological options for improving quality of life such as mild to moderate exercise. The main goal of this review is to provide an overview and outline the autonomic impacts of CRS and discuss renal denervation as a mechanism of potentially limiting or impairing the autonomic positive feedback loop initiated by disease progression and its likely subsequent amplification during exercise. Full article

Catecholamines are fundamental mediators of the stress response, regulating arousal, vigilance, and adaptive behavior. However, their dynamics under extreme real-life conditions remain insufficiently explored. Survival, Evasion, Resistance, and Escape (SERE) training provides a unique model for examining neuroendocrine mechanisms of adaptation during both the acute phase and the recovery period following intense psychological and physical stress. Serum norepinephrine (NE) and dopamine (DA) were measured in 47 special forces soldiers during peak stress in SERE and one month later, compared with 17 healthy controls. Samples were collected under standardized conditions and analyzed using validated ELISA kits. NE levels differed significantly among groups (p = 0.003), being higher during SERE training and in controls compared to the post-recovery condition. DA also showed a significant group effect (p < 0.001), with increased levels during recovery and in soldiers during SERE relative to controls. The post-recovery decline in norepinephrine suggests adaptive habituation of sympathetic activity following extreme stress exposure. Conversely, the sustained elevation of dopamine during recovery may reflect neuroadaptive mechanisms that promote motivational and cognitive restoration. Together, these findings indicate coordinated catecholaminergic regulation supporting long-term resilience in elite military personnel. Full article

Background/Objectives: One of the neurotoxic components from the sea trumpet polyps, Protopalythoa variabilis (Cnidaria, Anthozoa), is a 26-residue, V-shape helical peptide (PpVα). Its synthetic versions, i.e., the linear, the single-disulfide-bonded analog, and the chimeric peptide with a 6-residue stretch of the N-terminal native homologous peptide covalently linked to the linear sequence, were investigated for their activity on ion channels responsible for cellular excitability and synaptic transmission. Methods: Molecular docking analyses and dynamic simulations focused on the ability of PpVα peptides to bind ion channels selectively through interaction with critical residues at their binding sites. Results: Electrophysiological studies using the patch clamp technique with sympathetic bovine chromaffin cells from the adrenal medulla confirmed that PpVα analogs can block both sodium and calcium currents, which are responsible for initiating and propagating action potentials, respectively, and for neurotransmitter release. Additionally, the peptides displayed neuroprotective effects, attenuating cellular damage induced by veratridine, which interferes with sodium channel activity, and by oligomycin and rotenone (O/R), which affect mitochondrial function. Conclusions: The block of calcium and sodium channels and the neuroprotective effects against oxidative stress make the PpVα peptide scaffold an attractive template for developing agents that has significant clinical potential in several areas, such as the treatment of neurological diseases (epilepsy, multiple sclerosis, and neurodegenerative diseases), neuroprotection in acute events (stroke and traumatic brain or spinal cord injuries), the management of neuropathic pain, the prevention of ischemic damage, and psychiatric disorders (anxiety and bipolar disorder). Full article