Clinical Autonomic Research最新文献

Purpose: We conducted a meta-analysis to determine the effect of hyperoxia on muscle sympathetic nerve activity in healthy individuals and those with cardio-metabolic diseases.

Methods: A comprehensive search of electronic databases was performed until August 2022. All study designs (except reviews) were included: population (humans; apparently healthy or with at least one chronic disease); exposures (muscle sympathetic nerve activity during hyperoxia or hyperbaria); comparators (hyperoxia or hyperbaria vs. normoxia); and outcomes (muscle sympathetic nerve activity, heart rate, blood pressure, minute ventilation). Forty-nine studies were ultimately included in the meta-analysis.

Results: In healthy individuals, hyperoxia had no effect on sympathetic burst frequency (mean difference [MD] - 1.07 bursts/min; 95% confidence interval [CI] - 2.17, 0.04bursts/min; P = 0.06), burst incidence (MD 0.27 bursts/100 heartbeats [hb]; 95% CI - 2.10, 2.64 bursts/100 hb; P = 0.82), burst amplitude (P = 0.85), or total activity (P = 0.31). In those with chronic diseases, hyperoxia decreased burst frequency (MD - 5.57 bursts/min; 95% CI - 7.48, - 3.67 bursts/min; P < 0.001) and burst incidence (MD - 4.44 bursts/100 hb; 95% CI - 7.94, - 0.94 bursts/100 hb; P = 0.01), but had no effect on burst amplitude (P = 0.36) or total activity (P = 0.90). Our meta-regression analyses identified an inverse relationship between normoxic burst frequency and change in burst frequency with hyperoxia. In both groups, hyperoxia decreased heart rate but had no effect on any measure of blood pressure.

Conclusion: Hyperoxia does not change sympathetic activity in healthy humans. Conversely, in those with chronic diseases, hyperoxia decreases sympathetic activity. Regardless of disease status, resting sympathetic burst frequency predicts the degree of change in burst frequency, with larger decreases for those with higher resting activity.

Abstract

Increased sympathetic drive is of prognostic significance in chronic obstructive pulmonary disease (COPD) but its determinants remain poorly understood. One potential mechanism may be chemoreflex-mediated adrenergic stimulation caused by sustained hypercapnia. This study determined the impact of non-invasive ventilation (NIV) on muscle sympathetic nerve activity (MSNA) in patients with stable hypercapnic COPD. Ten patients (age 70 ± 7 years, GOLD stage 3–4) receiving long-term NIV (mean inspiratory positive airway pressure 21 ± 7 cmH₂O) underwent invasive MSNA measurement via the peroneal nerve during spontaneous breathing and NIV. Compared with spontaneous breathing, NIV significantly reduced hypercapnia (PaCO₂ 51.5 ± 6.9 vs 42.6 ± 6.1 mmHg, p < 0.0001) along with the burst rate (64.4 ± 20.9 vs 59.2 ± 19.9 bursts/min, p = 0.03) and burst incidence (81.7 ± 29.3 vs 74.1 ± 26.9 bursts/100 heartbeats, p = 0.04) of MSNA. This shows for the first time that correcting hypercapnia with NIV decreases MSNA in COPD.

Purpose

To review the available evidence on the impact of muscarinic receptor modulation on cardiovascular control in humans.

Methods

In this narrative Review we summarize data on cardiovascular endpoints from clinical trials of novel subtype-selective or quasi-selective muscarinic modulators, mostly PAMs, performed in the last decade. We also review the cardiovascular phenotype in recently described human genetic and autoimmune disorders affecting muscarinic receptors.

Results

Recent advancements in the development of compounds that selectively target muscarinic acetylcholine receptors are expanding our knowledge about the physiological function of each muscarinic receptor subtype (M1, M2, M3, M4, M5). Among these novel compounds, positive allosteric modulators (PAMs) have emerged as the preferred therapeutic to regulate muscarinic receptor subtype function. Many muscarinic allosteric and orthosteric modulators (including but not limited to xanomeline-trospium and emraclidine) are now in clinical development and approaching regulatory approval for multiple indications, including the treatment of cognitive and psychiatric symptoms in patients with schizophrenia as well as Alzheimer’s disease and other dementias. The results of these clinical trials provide an opportunity to understand the influence of muscarinic modulation on cardiovascular autonomic control in humans. While the results and the impact of each of these therapies on heart rate and blood pressure control have been variable, in part because the clinical trials were not specifically designed to measure cardiovascular endpoints, the emerging data is valuable to elucidate the relative cardiovascular contributions of each muscarinic receptor subtype.

Conclusion

Understanding the muscarinic control of cardiovascular function is of paramount importance and may contribute to the development of novel therapeutic strategies for treating cardiovascular disease.

Purpose: Increased vagal activity plays a prominent role in vasovagal syncope (VVS). The aim of this study was to characterize vagal function in VVS by evaluating the heart rate (HR) deceleration capacity (DC) and the HR deceleration runs (DRs) in patients with VVS between attacks.

Methods: A total of 188 consecutive VVS patients were enrolled in the study, of whom 129 had positive head-up tilt test (HUTT); 132 healthy participants were enrolled as controls. DC, DRs (DR2, i.e., episodes of 2 consecutive beat-to-beat HR decelerations), and the sum of DR8-10 (very long DR [VLDR]) were calculated using 24-h electrograms. Clinical characteristics, DC, and DRs were compared among syncope groups and controls.

Results: Patients with VVS had higher DC (10.63 ± 2.1 vs. 6.58 ± 1.7 ms; P < 0.001) and lower minimum HR and DR6-10 than controls. No significant differences in DC or DR6-10 were found between the patients with positive and those with negative HUTT results. In multivariate logistic regression analysis, minimum HR ≥ 40 bpm (odds ratio [OR] 0.408, 95% confidence interval [CI] 0.167-0.989; P = 0.048), daytime DC ≥ 7.37 ms (OR 3.040, 95% CI 1.220-7.576; P = 0.013), and VLDR ≥ 0.046% (OR 0.306, 95% CI 0.138-0.679; P = 0.004) were demonstrated to be risk factors significantly associated with VVS.

Conclusion: Compared to healthy controls, patients with VVS demonstrated distinct HR deceleration profiles between attacks, including overall higher DC and lower DR6-10.

Purpose: Young women are typically thought to be protected from cardiovascular disease (CVD) before menopause. However, posttraumatic stress disorder (PTSD) increases CVD risk in women by up to threefold. Data in predominantly male cohorts point to physiological mechanisms such as vascular and autonomic derangements as contributing to increased CVD risk. The purpose of the study reported here was to determine whether young women diagnosed with PTSD, compared to those without, present with arterial stiffness and impaired autonomic control of the heart.

Methods: A total of 73 healthy young women, ranging in age from 18 to 40 years, with a history of trauma exposure were included in this study, 32 with and 41 without a clinical PTSD diagnosis. We measured resting pulse wave velocity (PWV), central hemodynamics, augmentation pressure and augmentation index (AI) via pulse wave analysis using applanation tonometry. Heart rate variability was also assessed via peripheral arterial tone.

Results: In comparison to controls, women with PTSD showed higher central arterial pressure (mean ± standard deviation: systolic blood pressure 104 ± 8 vs. 97 ± 8 mmHg, p < 0.001; diastolic blood pressure 72 ± 7 vs. 67 ± 7 mmHg, p = 0.003), PWV (6 ± 0.3 vs. 5 ± 0.6 m/s, p < 0.001) and AI (22 ± 13 vs. 15 ± 12%, p = 0.007) but lower standard deviation of normal-to-normal intervals (SDNN; 44 ± 17 vs. 54 ± 18 ms, p = 0.005) and root mean square of successive differences between normal heartbeats (RMSSD; 37 ± 17 vs. 51 ± 22 ms, p = 0.002).

Conclusion: PTSD in young women is associated with higher brachial and central pressures, increased arterial stiffness and blunted parasympathetic control of the heart. These findings illustrate potential mechanisms underlying high risk for CVD in young women with PTSD, suggesting possible treatment targets for this at-risk group.