Autonomic Neuroscience-Basic & Clinical最新文献

Recent studies have demonstrated that muscle sympathetic nerve activity (MSNA) responses to isometric exercise differs between active and inactive limbs. Whether limb-dependent responses are characteristic of responses to the cold pressor test (CPT) remains to be established. Therefore, we tested the hypothesis that CPT-induced MSNA responses differ between affected and unaffected limbs such that MSNA in the affected lower limb is greater than MSNA responses in the contralateral lower limb and the upper limb. Integrated peroneal MSNA (microneurography) was measured in young healthy individuals (n = 10) at rest and during three separate 3-min CPTs: the microneurography foot, opposite foot, and opposite hand. Peak MSNA responses were extracted for further analysis, as well as corresponding hemodynamic outcomes including mean arterial pressure (MAP; Finometer). MSNA responses were greater when the microneurography foot was immersed in ice water than when the opposite foot was immersed (38 ± 18 vs 28 ± 16 bursts/100hb: P < 0.01). MSNA responses when the opposite hand was immersed were greater than both the microneurography foot (46 ± 22 vs 38 ± 18 bursts/100hb: P < 0.01) and opposite foot (46 ± 22 vs 28 ± 16 bursts/100hb: P ≤0.01). Likewise, MAP responses were greater during the hand CPT than the microneurography foot (99 ± 9 vs 96 ± 8 mmHg: P < 0.01) and opposite foot CPT (99 ± 9 vs 96 ± 9 mmHg: P < 0.01). These data indicate that (a) upper limbs and (b) immersed limbs elicit greater MSNA responses to the CPT than lower and/or non-immersed limbs.

Behaviors, emotions, and cardiovascular functions are influenced by stress. But these detrimental effects are not exclusive to an individual that directly experiences stress. Stress is also experienced vicariously through observation of another individual undergoing stress. The current study used the strong social bonds in socially monogamous prairie voles to determine effects of repeated vicarious stress on cardiac and behavioral outcomes. Male prairie voles were exposed to either a 5-minute open field chamber alone [separate (control)] or while concurrently witnessing their sibling undergo a tail-suspension stressor [concurrent (experimental)], repeated across 4 sessions. Cardiac responses in animals in the open field were evaluated for heart rate and heart rate variability prior to, during, and after each test session, and behaviors were evaluated for motion, exploration, stress reactivity, and anxiety-relevant behaviors during each test session. The concurrent condition (versus separate) displayed increased heart rate and reduced heart rate variability during repeated test sessions, and impaired recovery of these parameters following the test sessions. The pattern of disturbances suggests that both increased sympathetic and reduced parasympathetic influence contributed to the cardiac responses. Animals in the concurrent condition (versus separate) displayed disrupted rearing, grooming, and motion; reduced duration of center section exploration; and increased freezing responses across repeated test sessions. Collectively, cardiac and behavioral stress reactivity are increased as a function of vicarious stress in prairie voles, which are evident across repeated experiences of stress. These results inform our understanding of the experience of vicarious stress in social species, including humans.

Background

Vasovagal syncope (VVS) is a prevalent condition characterized by a sudden drop in blood pressure and heart rate, leading to a brief loss of consciousness and postural control. Recurrent episodes of VVS significantly impact the quality of life and are a common reason for emergency department visits. Non-pharmacological interventions, such as tilt training, physical counter pressure maneuvers, and yoga, have been proposed as potential treatments for VVS. However, their efficacy in preventing VVS remains uncertain.

Methods

A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Web of Science, and Embase were searched up to March 2023 for randomized controlled trials comparing non-pharmacological interventions with control in preventing VVS recurrence. The primary outcome was the recurrence rate of VVS episodes.

Results

A total of 1130 participants from 18 studies were included in the meta-analysis. The overall mean effect size for non-pharmacological interventions versus control was 0.245 (95 % CI: 0.128–0.471, p-value <0.001). Subgroup analysis showed that yoga had the largest effect size (odds ratio 0.068, 95 % CI: 0.018–0.250), while tilt training had the lowest effect size (odds ratio 0.402, 95 % CI: 0.171–0.946) compared to control. Physical counter pressure maneuvers demonstrated an odds ratio of 0.294 (95 % CI: 0.165–0.524) compared to control.

Conclusion

Non-pharmacological interventions show promise in preventing recurrent VVS episodes. Yoga, physical counter pressure maneuvers, and tilt training can be considered as viable treatment options. Further research, including randomized studies comparing pharmacological and non-pharmacological approaches, is needed to evaluate the safety and efficacy of these interventions for VVS treatment.

The sensitization and hypertonicity of visceral afferents are highly relevant to the development and progression of cardiovascular and respiratory disease states. In this review, we described the evidence that the inflammatory process regulates visceral afferent sensitivity and tonicity, affecting the control of the cardiovascular and respiratory system. Some inflammatory mediators like nitric oxide, angiotensin II, endothelin-1, and arginine vasopressin may inhibit baroreceptor afferents and contribute to the baroreflex impairment observed in cardiovascular diseases. Cytokines may act directly on peripheral afferent terminals that transmit information to the central nervous system (CNS). TLR-4 receptors, which recognize lipopolysaccharide, were identified in the nodose and petrosal ganglion and have been implicated in disrupting the blood-brain barrier, which can potentiate the inflammatory process. For example, cytokines may cross the blood-brain barrier to access the CNS. Additionally, pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α and some of their receptors have been identified in the nodose ganglion and carotid body. These pro-inflammatory cytokines also sensitize the dorsal root ganglion or are released in the nucleus of the solitary tract. In cardiovascular disease, pro-inflammatory mediators increase in the brain, heart, vessels, and plasma and may act locally or systemically to activate/sensitize afferent nervous terminals. Recent evidence demonstrated that the carotid body chemoreceptor cells might sense systemic pro-inflammatory molecules, supporting the novel proposal that the carotid body is part of the afferent pathway in the central anti-inflammatory reflexes. The exact mechanisms of how pro-inflammatory mediators affects visceral afferent signals and contribute to the pathophysiology of cardiovascular diseases awaits future research.

Cancer cachexia, characterized by muscle wasting and widespread inflammation, poses a significant challenge for patients with cancer, profoundly impacting both their quality of life and treatment management. However, existing treatment modalities remain very limited, accentuating the necessity for innovative therapeutic interventions. Many recent studies demonstrated that changes in autonomic balance is a key driver of cancer cachexia. This review consolidates research findings from investigations into autonomic dysfunction across cancer cachexia, spanning animal models and patient cohorts. Moreover, we explore therapeutic strategies involving adrenergic receptor modulation through receptor blockers and agonists. Mechanisms underlying adrenergic hyperactivity in cardiac and adipose tissues, influencing tissue remodeling, are also examined. Looking ahead, we present a perspective for future research that delves into autonomic dysregulation in cancer cachexia. This comprehensive review highlights the urgency of advancing research to unveil innovative avenues for combatting cancer cachexia and improving patient well-being.

Introduction

Approximately 50 % of residents in long-term care facilities fall yearly and orthostatic hypotension accounts for a significant portion of them. Neurogenic orthostatic hypotension - a subtype of orthostatic hypotension – is important to be recognized as its management is far more complex; undertreatment of these older adults can lead to recurrent falls, high healthcare cost burden, and increased morbidity and mortality. The primary purpose of our study was to describe the rate of neurogenic orthostatic hypotension in older adults in a long-term care facility, with a secondary purpose to describe risk factors for neurogenic orthostatic hypotension in this population.

Methods

We conducted a retrospective case-control study of residents with recurrent falls at the Dayton Veteran's Affairs long-term care facility. Charts were manually reviewed. Inclusion criterion was three or more falls and age 65 or greater; we did not have exclusion criteria.

ICD10 codes and most recent primary care physician notes were used to identify comorbidity diagnoses. Recent orthostatic vitals were used to assess orthostatic hypotension or neurogenic orthostatic hypotension diagnoses.

Results

Of our sample of 224 residents, we observed a prevalence of 20.5 % for neurogenic orthostatic hypotension and 32.1 % for orthostatic hypotension. Neither of them had diagnosis of neurogenic orthostatic hypotension documented. Parkinson's disease was associated with neurogenic orthostatic hypotension (OR-4.3; p = 0.002). Hypertension was prevalent in 69.6 % of residents with orthostatic vitals suggestive of neurogenic orthostatic hypotension.

Conclusion

Older adults with recurrent falls at a long-term care facility meet criteria for neurogenic orthostatic hypotension diagnosis far more often than is documented. Common comorbidities associated with neurogenic orthostatic hypotension in this population include Parkinson's disease.

Renal nerves and their role in physiology and disease have been a topic of increasing interest in the past few decades. Renal inflammation contributes to many cardiorenal disease conditions, including hypertension, chronic kidney disease, and polycystic kidney disease. Much is known about the role of renal sympathetic nerves in physiology – they contribute to the regulation of sodium reabsorption, renin release, and renal vascular resistance. In contrast, far less is known about afferent, or “sensory,” renal nerves, which convey signals from the kidney to the brain. While much remains unknown about these nerves in the context of normal physiology, even less is known about their contribution to disease states. Furthermore, it has become apparent that the crosstalk between renal nerves and the immune system may augment or modulate disease. Research from other fields, especially pain research, has provided critical insight into neuroimmune crosstalk. Sympathetic renal nerve activity may increase immune cell recruitment, but far less work has been done investigating the interplay between afferent renal nerves and the immune system. Evidence from other fields suggests that inflammation may augment afferent renal nerve activity. Furthermore, these nerves may exacerbate renal inflammation through the release of afferent-specific neurotransmitters.

Purpose

Remodeling of sympathetic nerves and ACE2 has been implicated in cardiac pathology, and ACE2 also serves as a receptor for SARS-CoV-2. However, there is limited histological knowledge about the transmural distribution of sympathetic nerves and the cellular localization and distribution of ACE2 in human left ventricles from normal or diseased hearts. Goals of this study were to establish the normal pattern for these parameters and determine changes that occurred in decedents with cardiovascular disease alone compared to those with cardiac pathology and severe COVID-19.

Methods

We performed immunohistochemical analysis on sections of left ventricular wall from twenty autopsied human hearts consisting of a control group, a cardiovascular disease group, and COVID-19 ARDS, and COVID-19 non-ARDS groups.

Results

Using tyrosine hydroxylase as a noradrenergic marker, we found substantial sympathetic nerve loss in cardiovascular disease samples compared to controls. Additionally, we found heterogeneous nerve loss in both COVID-19 groups. Using an ACE2 antibody, we observed robust transmural staining localized to pericytes in the control group. The cardiovascular disease hearts displayed regional loss of ACE2 in pericytes and regional increases in staining of cardiomyocytes for ACE2. Similar changes were observed in both COVID-19 groups.

Conclusions

Heterogeneity of sympathetic innervation, which occurs in cardiac disease and is not increased by severe COVID-19, could contribute to arrhythmogenesis. The dominant localization of ACE2 to pericytes suggests that these cells would be the primary target for potential cardiac infection by SARS-CoV-2. Regional changes in ACE2 staining by myocytes and pericytes could have complex effects on cardiac pathophysiology.

Purpose

To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination.

Methods

We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series.

Results

We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05).

Conclusion

Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.

The temporal response of changes in renal sodium reabsorption during increased renal sympathetic nerve activity has not been investigated. Central hypovolemia by application of lower-body negative-pressure (LBNP) elicits baroreceptor mediated sympathetic reflexes to maintain arterial blood pressure. We hypothesized, that during 90 min LBNP, the renal sodium retention would increase rapidly, remain increased during intervention, and return to baseline immediately after end of intervention.

Methods

30 young, healthy, sodium loaded, non-obese males were exposed to −15 mmHg LBNP, −30 mmHg LBNP, −15 mmHg LBNP + renin blockade or time-control (0 mmHg LBNP) for 90 min. Urine was collected every 15 min during 90 min of intervention and 60 min of recovery to identify a possible relation between time of intervention and renal response.

Results

All intervention groups exhibited a comparable reduction in distal sodium excretion at the end of the intervention (P = 0.46 between groups; −15 mmHg: −3.1 ± 0.9 %, −30 mmHg: −2.9 ± 0.6 %, −15 mmHg + aslikiren: −1.8 ± 0.6 %). −15 mmHg+Aliskiren resulted in a slower onset, but all groups exhibited a continued reduction in sodium excretion after 1 h of recovery despite return to baseline of renin, aldosterone, diuresis and cardiovascular parameters.

Conclusion

Sympathetic stimulation for 90 min via LBNP at −30 mmHg LBNP compared to −15 mmHg did not result in a greater response in fractional Na⁺ excretion, suggesting that additional baroreceptor unloading did not cause further increases in renal sodium reabsorption. Changes in distal Na⁺ excretion were linear with respect to time (dose) of intervention, but seem to exhibit a saturation-like effect at a level around 4 %. The lack of recovery after 1 h is also a new finding that warrants further investigation.