Autonomic Neuroscience-Basic & Clinical最新文献

Background

Many patients with postural orthostatic tachycardia syndrome (POTS) are hypovolemic with plasma volume deficits of 10–30 %. Some also have low levels of aldosterone and diminished aldosterone-renin ratios despite elevations in angiotensin II, pointing to potential adrenal dysfunction. To assess adrenal gland responsiveness in POTS, we measured circulating levels of aldosterone and cortisol following adrenocorticotropin hormone (ACTH) stimulation.

Methods

While on a low Na⁺ diet (∼10 mEq/day), 8 female patients with POTS and 5 female healthy controls (HC) received a low dose (1 μg) ACTH bolus following a baseline blood sample. After 60 min, a high dose (249 μg) infusion of ACTH was administered to ensure maximal adrenal response. Venous aldosterone and cortisol levels were sampled every 30 min for 2 h.

Results

Aldosterone increased in both groups in response to ACTH but was not different between POTS vs. HC at 60 min (53.5 ng/dL [37.8–61.8 ng/dL] vs. 46.1 ng/dL [36.7–84.9 ng/dL]; P = 1.000) or maximally (56.4 ng/dL [49.2–67.1 ng/dL] vs. 49.5 ng/dL [39.1–82.8 ng/dL]; P = 0.524). Cortisol increased in both groups in response to ACTH but was not different in patients with POTS vs. HC at 60 min (39.9 μg/dL [36.1–47.7 μg/dL] vs. 39.3 μg/dL [35.4–46.6 μg/dL]; P = 0.724) or maximally (39.9 μg/dL [33.9–45.4 μg/dL] vs. 42.0 μg/dL [37.6–49.7 μg/dL]; P = 0.354).

Conclusions

ACTH appropriately increased the aldosterone and cortisol levels in patients with POTS. These findings suggest that the response of the adrenal cortex to hormonal stimulation is intact in patients with POTS.

Previous studies from our laboratory have shown that the pressor response to intracerebroventricular (icv) administered ANG II in normotensive rats or spontaneously hypertensive rats (SHRs) is attenuated by increased central H₂O₂ concentration, produced either by direct H₂O₂ icv injection or by increased endogenous H₂O₂ centrally in response to local catalase inhibition with 3-amino-1,2,4-triazole (ATZ). In the present study, we evaluated the effects of ATZ administered peripherally on arterial pressure and sympathetic and angiotensinergic activity in SHRs. Male SHRs weighing 280–330 g were used. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving SHRs. Acute intravenous injection of ATZ (300 mg/kg of body weight) did not modify MAP and HR during the next 4 h, however, the treatment with ATZ (300 mg/kg of body weight twice per day) for 3 days reduced MAP (144 ± 6, vs. saline, 183 ± 13 mmHg), without changing HR. Intravenous hexamethonium (ganglionic blocker) produced a smaller decrease in MAP 4 h after ATZ (−25 ± 3, vs saline −38 ± 4 mmHg). Losartan (angiotensinergic AT₁ receptor blocker) produced a significant depressor response 4 h after ATZ (−22 ± 4, vs. saline: −2 ± 4 mmHg) and in 3-day ATZ treated SHRs (−25 ± 5, vs. saline: −9 ± 4 mmHg). The results suggest that the treatment with ATZ reduces sympathetic activity in SHRs and simultaneously increases angiotensinergic activity.

Patients with type 2 diabetes mellitus (T2DM) have impaired arterial baroreflex function, which may be linked to the co-existence of obesity. However, the role of obesity and its related metabolic impairments on baroreflex dysfunction in T2DM is unknown. This study aimed to investigate the role of visceral fat and adiponectin, the most abundant cytokine produced by adipocytes, on baroreflex dysfunction in T2DM rats. Experiments were performed in adult male UCD-T2DM rats assigned to the following experimental groups (n = 6 in each): prediabetic (Pre), diabetes-onset (T0), 4 weeks after onset (T4), and 12 weeks after onset (T12). Age-matched healthy Sprague-Dawley rats were used as controls. Rats were anesthetized and blood pressure was directly measured on a beat-to-beat basis to assess spontaneous baroreflex sensitivity (BRS) using the sequence technique. Dual-energy X-ray absorptiometry (DEXA) was used to assess body composition. Data are presented as mean ± SD. BRS was significantly lower in T2DM rats compared with controls at T0 (T2D: 3.7 ± 3.2 ms/mmHg vs Healthy: 16.1 ± 8.4 ms/mmHg; P = 0.01), but not at T12 (T2D: 13.4 ± 8.1 ms/mmHg vs Healthy: 9.2 ± 6.0 ms/mmHg; P = 0.16). T2DM rats had higher visceral fat mass, adiponectin, and insulin concentrations compared with control rats (all P < 0.01). Changes in adiponectin and insulin concentrations over the measured time-points mirrored one another and were opposite those of the BRS in T2DM rats. These findings demonstrate that obesity-related metabolic impairments may contribute to an attenuated spontaneous BRS in T2DM, suggesting a link between metabolic and autonomic dysfunction.

Aim

to analyze the quality of sleep and cardiac autonomic modulation of elderly diabetic women in the post-covid-19 syndrome.

Methodology

41 elderly women, aged 60–75 years, with a diagnosis of Type 2 Diabetes Mellitus and who had covid-19 were included, divided into three groups: 14 in the Diabetes without covid-19 group (DG), 15 in the Diabetes with covid-19 group (CG), 12 in the Diabetes with covid-19 group who had Pulmonary Compromise (IG). Sleep quality was assessed using the Pittsburgh questionnaire, anamnesis, capillary blood glucose, blood pressure collection, anthropometry, resting electrocardiogram for 10 min for heart rate variability (HRV) analysis. Data were analyzed by 1-way ANOVA followed by Tukey-Kramer Multiple Comparisons Test, significance for p ≤ 0.05.

Results

there was no significant difference in age, blood glucose, blood pressure, and body composition between the groups. In the analysis of sleep quality, there was significance in the following indices: sleep duration, sleep efficiency, sleep disturbances, and daytime sleepiness. Further, there was a reduction in autonomic indices between CG vs. DG: VarRR (ms²), SDNN (ms), SD1 (ms), TINN (ms), HF-log (ms²), LF-log (ms²); and between IG vs. DG: VarRR (ms²), SDNN (ms), RMSSD (ms), SD1 (ms), SD2 (ms), and HF-log (ms²).

Conclusion

it is suggestive that diabetic elderly women who had covid-19, with and without pulmonary impairment, have impaired sleep quality and interference on HRV with decreased parasympathetic autonomic modulation.

Purpose

The autonomic nervous system interacts with the immune system via the inflammatory response. Heart rate variability (HRV), a marker of autonomic activity, is associated with inflammation, and nosocomial infections/sepsis, and has clinical implications for the monitoring of at-risk patients. Due to the vagal tone's influence on anti-inflammatory immune response, this association may predominately be reflected by vagally-mediated HRV indices. However, HRV's predictive significance on inflammation/infection remains unclear.

Methods

843 studies examining the associations/prognostic value of HRV indices on inflammation, and nosocomial infection/sepsis were screened in this systematic review. According to inclusion and exclusion criteria, 68 associative studies and 14 prediction studies were included.

Results

HRV and pro-inflammatory state were consistently associated in healthy subjects and patient groups. Pro-inflammatory state was related to reduced total power HRV including vagally- and non-vagally-mediated HRV indices. Similar, compared to controls, HRV reductions were observed during nosocomial infections/sepsis.

Only limited evidence supports the predictive value of HRV in the development of nosocomial infections/sepsis. Reduced very low frequency power HRV showed the highest predictive value in adults, even with different clinical conditions. In neonates, an increased heart rate characteristic score, combining reduced total power HRV, decreased complexity, and vagally-dominated asymmetry, predicted sepsis.

Conclusions

Pro-inflammatory state is related to an overall reduction in HRV rather than a singular reduction in vagally-mediated HRV indices, reflecting the complex autonomic-regulatory changes occurring during inflammation.

The potential benefit of using continuous HRV monitoring for detecting nosocomial infection-related states, and the implications for clinical outcome, need further clarification.

Transient receptor potential melastatin 3 (TRPM3) channels contribute to nodose afferent and brainstem nucleus tractus solitarii (nTS) activity. Exposure to short, sustained hypoxia (SH) and chronic intermittent hypoxia (CIH) enhances nTS activity, although the mechanisms are unknown. We hypothesized TRPM3 may contribute to increased neuronal activity in nTS-projecting nodose ganglia viscerosensory neurons, and its influence is elevated following hypoxia. Rats were exposed to either room air (normoxia), 24-h of 10 % O₂ (SH), or CIH (episodic 6 % O₂ for 10d). A subset of neurons from normoxic rats were exposed to in vitro incubation for 24-h in 21 % or 1 % O₂. Intracellular Ca²⁺ of dissociated neurons was monitored via Fura-2 imaging. Ca²⁺ levels increased upon TRPM3 activation via Pregnenolone sulfate (Preg) or CIM0216. Preg responses were eliminated by the TRPM3 antagonist ononetin, confirming agonist specificity. Removal of extracellular Ca²⁺ also eliminated Preg response, further suggesting Ca²⁺ influx via membrane-bound channels. In neurons isolated from SH-exposed rats, the TRPM3 elevation of Ca²⁺ was greater than in normoxic-exposed rats. The SH increase was reversed following a subsequent normoxic exposure. RNAScope demonstrated TRPM3 mRNA was greater after SH than in Norm ganglia. Incubating dissociated cultures from normoxic rats in 1 % O₂ (24-h) did not alter the Preg Ca²⁺ responses compared to their normoxic controls. In contrast to in vivo SH, 10d CIH did not alter TRPM3 elevation of Ca²⁺. Altogether, these results demonstrate a hypoxia-specific increase in TRPM3-mediated calcium influx.

Objective

Post-acute sequelae of SARS-COV-2 (PASC) are emerging as a major health challenge. Orthostatic intolerance secondary to autonomic failure has been found in PASC patients. This study investigated the effect of COVID-19 after recovery on blood pressure (BP) during the orthostatic challenge.

Research design and methods

Thirty-one out of 45 patients hospitalized due to COVID-19-related pneumonia that developed PASC and did not have hypertension at discharge were studied. They underwent a head-up tilt test (HUTT) at 10.8 ± 1.9 months from discharge. All met the PASC clinical criteria, and an alternative diagnosis did not explain the symptoms. This population was compared with 32 historical asymptomatic healthy controls.

Results

Exaggerated orthostatic blood pressure response (EOPR)/orthostatic hypertension (OHT) was detected in 8 out of 23 (34.7 %) patients, representing a significantly increased prevalence (7.67-fold increase p = 0.009) compared to 2 out of 32 (6.4 %) asymptomatic healthy controls matched by age, who underwent HUTT and were not infected with SARS-CoV-2.

Conclusions

This prospective evaluation in patients with PASC revealed abnormal blood pressure rise during the orthostatic challenge, suggesting of autonomic dysfunction in a third of the studied subjects. Our findings support the hypothesis that EOPR/OHT may be a phenotype of neurogenic hypertension. Hypertension in PASC patients may adversely affect the cardiovascular burden in the world.

Autonomic dysfunction has been observed in Alzheimer's disease (AD); however, the effects of genes involved in AD on the peripheral nervous system are not well understood. Previous studies have shown that presenilin-1 (PSEN1), the catalytic subunit of the gamma secretase (γ-secretase) complex, mutations in which are associated with familial AD function, regulates dendritic growth in hippocampal neurons. In this study, we examined whether the γ-secretase pathway also influences dendritic growth in primary sympathetic neurons. Using immunoblotting and immunocytochemistry, molecules of the γ-secretase complex, PSEN1, PSEN2, PEN2, nicastrin and APH1a, were detected in sympathetic neurons dissociated from embryonic (E20/21) rat sympathetic ganglia. Addition of bone morphogenetic protein-7 (BMP-7), which induces dendrites in these neurons, did not alter expression or localization of γ-secretase complex proteins. BMP-7-induced dendritic growth was inhibited by siRNA knockdown of PSEN1 and by three γ-secretase inhibitors, γ-secretase inhibitor IX (DAPT), LY-411575 and BMS-299897. These effects were specific to dendrites and concentration-dependent and did not alter early downstream pathways of BMP signaling. In summary, our results indicate that γ-secretase activity enhances BMP-7 induced dendritic growth in sympathetic neurons. These findings provide insight into the normal cellular role of the γ-secretase complex in sympathetic neurons.