Clinical Autonomic Research最新文献

Purpose: Despite the central role of exercise in treating postural orthostatic tachycardia syndrome (POTS) there have been no studies on the subjective experience of exercise interventions and/or recommendations among this patient population. The purpose of this mixed-methods study was to provide greater understanding of the perceived barriers, preferences, perceptions of exercise, and experiences implementing exercise recommendations for adults with POTS in order to optimize treatment recommendations and intervention design.

Methods: This study consisted of a series of focus groups (n = 29) and an online survey of adults with POTS (n = 255) focusing on exercise engagement, beliefs, barriers, and facilitators. Qualitative data were analyzed using an iterative inductive-deductive approach, informed by social cognitive theory, which resulted in a conceptual framework and a series of themes.

Results: Survey results showed that participants reported a wide range of exercise frequency prior to the onset of POTS symptoms, and overall lower exercise engagement post-POTS. In both survey results and qualitative findings, participants reported believing that exercise is important in managing POTS, but identified barriers to exercise training, including most saliently, their symptom burden. Participants also identified important needs and facilitating factors that could support them in engaging in regular exercise to help manage their condition.

Conclusion: These findings shed light on the patient experience of exercise in POTS, which can inform both the tailoring of exercise recommendations and the design of interventions to support exercise engagement specific to the POTS population.

Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright position in the absence of orthostatic hypotension, defined as a sustained decrease in systolic blood pressure (SBP) of ≥ 20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 min of standing. In children, a sustained HR increment of at least 40 bpm is required for diagnosis of POTS. POTS is a common condition in adults and children suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In daily clinical practice, therapeutic recommendations are rare and evidence is missing. The objective of this review is to present the current knowledge on non-pharmacological and pharmacological approaches in POTS with a special focus on POTS therapy in children and people with ME/CFS. Of 3853 studies, 45 studies were included in the systematic review. Evidence on therapy in POTS is rare and large randomized controlled trials (RCT) on single interventions are needed. Non-pharmacological approaches such as the use of compression garments, physical training, salt supplementation and transdermal vagal nerve stimulation could be possible treatment options in POTS because they are easy to implement as first-line therapeutic measures in clinical practice. For pharmaceuticals, several studies showed significant effects following therapy with ivabradine and β-adrenergic blocking agents. There are single studies which imply that midodrine (hydrochloride) and pyridostigmine seem to have a beneficial effect on hemodynamics in POTS.

Purpose: To explore changes in sympathetic nerve activity in anxiety, clarify mechanisms underlying increased sympathetic discharge, and evaluate an electrocardiogram (ECG)-derived high-frequency signal, termed skin sympathetic nerve activity (SKNA), as a potential noninvasive correlate of sympathetic outflow.

Methods: Male Sprague-Dawley rats (n = 120) were divided into control and chronic unpredictable mild stress (CUMS) groups (n = 60 each). Anxiety-like behavior was assessed using the open field test and elevated plus maze. Stellate ganglion nerve activity (SGNA) and SKNA were recorded. The relationship between SGNA and SKNA was assessed in both time and frequency domains. The NMDAR1 inhibitor AP-5, Tat-fused α2δ-1 C-terminal peptide, or control peptide were microinjected into the hypothalamic paraventricular nucleus (PVN). PVN expression of GluN1 and α2δ-1 was analyzed via qPCR, western blotting, and co-immunoprecipitation. Plasma norepinephrine (NE) and corticosterone (CORT) levels were measured by ELISA.

Results: CUMS rats showed significant anxiety-like behaviors (reduced center time and open arm entries, p < 0.001), along with elevated SGNA and SKNA (p < 0.001). SGNA and SKNA were significantly correlated in the time domain (r = 0.538, p < 0.001) and showed strong concordance in their power spectral density (PSD) profiles, though not linear coherence. PVN GluN1 and α2δ-1 mRNA and protein levels were upregulated, with enhanced interaction. AP-5 and the Tat-fused α2δ-1 peptide normalized SGNA/SKNA in CUMS rats. No further reduction was seen when both were applied sequentially. Control peptide had no effect.

Conclusion: Anxiety increases sympathetic activity via upregulation of the PVN α2δ-1-NMDAR1 complex. SKNA is an ECG-derived high-frequency signal that correlates with SGNA under anesthesia and shows potential as a noninvasive index for sympathetic function in anxiety research.

Purpose: Spontaneous indices have been widely used to assess baroreflex gain despite their numerous limitations and concerns regarding their validity, reliability, and reproducibility. In this retrospective study, we investigated whether spontaneous baroreflex indices reflect cardiovagal baroreflex gain assessed by the neck-chamber technique in those with spinal cord injury (SCI) and in uninjured individuals. SCI represents a model of preserved cardiovagal baroreflex control coupled with impaired sympathetic effects on the vasculature.

Methods: We derived three spontaneous indices of baroreflex sensitivity (sequence method, low-frequency (LF), and high-frequency (HF) transfer function) and compared them with baroreflex gain obtained via the neck-chamber technique in adults with SCI (n = 29; neurological level C1-T10, ≤ 2 years since injury) and uninjured adults (n = 14).

Results: In both groups, spontaneous indices were highly correlated with each other (all p < 0.01). In uninjured participants, neck suction baroreflex gain did not relate to any spontaneous index. In individuals with SCI, neck-chamber gain correlated significantly with spontaneous indices (all r > 0.43, p < 0.05); these relationships were significantly stronger in individuals with neurologically complete injuries (sequence: r = 0.67, p < 0.01; LF: r = 0.79, p < 0.001; HF: r = 0.76, p < 0.001). However, Bland-Altman analysis revealed a strong proportional bias, with spontaneous indices consistently and progressively overestimating neck-chamber gain (all r > 0.91, p < 0.001).

Conclusions: These results suggest that sympathetic activity is largely responsible for the lack of correspondence between spontaneous and neck-chamber baroreflex gains. However, even in individuals with a neurologically complete SCI, where sympathetic influences are minimal, spontaneous indices may not consistently reflect baroreflex gain derived from other methods.

Purpose: Cardiovascular autonomic failure and neurogenic orthostatic hypotension (nOH) are common and disabling in Parkinson's disease (PD) and multiple system atrophy (MSA). Recent studies have shown evidence of postganglionic autonomic denervation in MSA as well as PD. We aimed to characterise the relationship between nOH, autonomic failure and postganglionic denervation in PD and MSA. We hypothesised that postganglionic autonomic denervation contributes to the development of nOH and correlates with the severity of cardiovascular autonomic failure.

Methods: We assessed 57 patients (37 PD, 20 MSA, median 64 [IQR 59-70] years) with cardiovascular autonomic testing; dynamic sweat testing; plasma noradrenaline levels; skin biopsies for quantification of intraepidermal, pilomotor and sudomotor innervation; and autonomic symptom questionnaires.

Results: Overall, 78% of patients with MSA and 36% with PD had nOH ≥ 20/10 mmHg. The MSA group had more severe nOH, sudomotor dysfunction and cutaneous denervation, with higher supine noradrenaline than the PD group. Only supine noradrenaline differed between MSA and PD with nOH subgroups (P = 0.04). Overall, patients with nOH demonstrated more severe (1) cardiovascular autonomic failure, with reduced pressor responses to isometric exercise, deep breathing and Valsalva ratio; (2) intraepidermal, pilomotor and sudomotor denervation; and (3) autonomic symptoms and Hoehn-Yahr grade. The severity of nOH and cardiovascular autonomic failure correlated with autonomic denervation, patient symptoms and Hoehn-Yahr grade (ρ ≥ 0.50).

Conclusions: nOH was associated with cutaneous autonomic denervation in both PD and MSA, with correlations between cardiovascular autonomic failure, cutaneous denervation and Hoehn-Yahr grade. Postganglionic autonomic denervation may contribute to nOH in PD and MSA, and affect responses to therapeutic agents.