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Comparison of endothelial function and sympathetic nervous system activity along the glucose continuum in individuals with differing metabolic risk profiles and low dietary sodium intake.
Baqar, S, Straznicky, NE, Lambert, G, Kong, YW, Dixon, JB, Jerums, G, Ekinci, EI, Lambert, E
BMJ open diabetes research & care. 2019;(1):e000606
Abstract
OBJECTIVE Low sodium intake may trigger sympathetic nervous system (SNS) activation and endothelial dysfunction. Studies have not explored these associations along the glucose continuum. Accordingly, we compared endothelial function and SNS activity in individuals with low sodium intake and differing categories of metabolic risk along the glucose continuum. We hypothesized that low sodium intake is associated with (1) impairment of endothelial function and (2) higher SNS activity in individuals with higher metabolic risk. RESEARCH DESIGN AND METHODS In this prospective observational study, participants (n=54) with low sodium intake (single 24 hours urine sodium excretion <150 mmol/24 hours) were categorized based on oral glucose tolerance testing as: normal glucose tolerance (NGT, n=10), impaired glucose tolerance (IGT, n=15), treatment naive type 2 diabetes (T2D-) (n=12) or treated type 2 diabetes (T2D+) (n=17). We assessed endothelial function using pulse amplitude tonometry (PAT) derived reactive hyperemic index and PAT ratio; arterial stiffness via augmentation index; muscle sympathetic nerve activity (MSNA) using microneurography; cardiac baroreflex; heart rate; blood pressure; glycosylated hemoglobin A1c (HbA1c) and lipid profile. RESULTS Mean (SD) sodium excretion was 110.6 (26) mmol/24 hours. Compared with NGT, IGT and T2D-, the T2D+ group had lower MSNA (p=0.005), PAT ratio (p=0.04) and baroreflex sensitivity (p=0.0002) and an augmented heart rate (p=0.02). The T2D+ group had appropriate mean (SD) glycemic (HbA1c 7.2 (1.72)%), total cholesterol (4.2 (1.0) mmol/L), low-density lipoprotein (2.2 (1.0) mmol/L) and blood pressure (systolic 136 (13), diastolic 78 (12)) (mm Hg) control. CONCLUSIONS Individuals with T2D+ have impaired endothelial and baroreflex function, despite low sodium intake, appropriately managed cardiometabolic risk factors and lower SNS activity, compared with others along the glucose continuum. Whether low sodium intake is associated with modulation of the sympathovascular profile in T2D requires further investigation.
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Impact of short-acting loop diuretic doses and cardiac sympathetic nerve abnormalities on outcomes of patients with reduced left ventricular function.
Onitsuka, H, Koyama, S, Ideguchi, T, Ishikawa, T, Kitamura, K, Nagamachi, S
Medicine. 2019;(8):e14657
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Abstract
Recent studies reported that high doses of short-acting loop diuretics are associated with poor outcomes in patients with heart failure (HF). Short-acting loop diuretics have been shown to activate the renin-angiotensin system (RAS) and have no favorable effects on cardiac sympathetic nervous system (SNS) activity. The goal of this study is to investigate the relationship between daily doses of furosemide and the outcomes of patients with left ventricular dysfunction (LVD) from the viewpoint of cardiac SNS abnormalities using iodine-123-labeled metaiodobenzylguanidine (l-MIBG) myocardial scintigraphy.We enrolled 137 hospitalized patients (62.5 ± 14.2 years old, 103 men) with LVEF < 45% who underwent l-MIBG myocardial scintigraphy. A delayed heart-to-mediastinum ratio (delayed HMR) was assessed using l-MIBG scintigraphy. Cardiac events were defined as cardiac death or re-hospitalization due to the deterioration of HF. Cox proportional hazard analysis was used to identify predictors of cardiac events.Cardiac events occurred in 57 patients in a follow-up period of 33.1 ± 30 months. In a multivariate Cox proportional hazard analysis, delayed HMR and furosemide doses were identified as independent predictors of cardiac events (P = .0042, P = .033, respectively). Inverse probability of treatment weighting Cox modeling showed that the use of furosemide (≥40 mg /day) was associated with cardiac events with a hazard ratio of 1.96 (P = .003). In the Kaplan-Mayer analysis, the cardiac event-free survival rate was significantly lower in patients treated with high doses of furosemide (≥60 mg/day vs 40-60 mg/day vs <40 mg/day, the Log-rank test P < .0001). In a receiver-operating characteristic (ROC) analysis, the cut-off value for cardiac events was 40 mg/day of furosemide. The cardiac event-free rate was significantly lower in patients with delayed HMR <1.8 (median value) and receiving furosemide ≥40 mg/day than in other patients (the Log-rank test P < .0001). Significant differences in cardiac event rates according to furosemide doses among patients with delayed HMR <1.8 were observed among patients without β-blocker therapy (P = .001), but not among those with β-blocker therapy (P = .127).The present results indicate that a relationship exists between higher doses of furosemide and poor outcomes. The prognosis of HF patients with severe cardiac SNS abnormalities receiving high-dose short-acting loop diuretics is poor.
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Exploring the complexity: the interplay between the angiotensin-converting enzyme insertion/deletion polymorphism and the sympathetic response to hemodialysis.
Ribas Ribeiro, L, Flores de Oliveira, J, Bueno Orcy, R, Castilho Barros, C, Damé Hense, J, Santos, F, Irigoyen, MC, Gonzalez, MC, Oses, JP, Böhlke, M
American journal of physiology. Heart and circulatory physiology. 2018;(4):H1002-H1011
Abstract
Patients on hemodialysis (HD) are at increased risk for arrhythmias and sudden cardiac death. Autonomic nervous system (ANS) dysfunction seems to participate in the arrhythmogenic process. Genetic factors have an impact on ANS modulation, but the specific role of the insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) has not been investigated. Since the D allele increases gene expression, it is a candidate polymorphism to interact with the ANS. The aim of the present study was to compare the behavior of heart rate variability (HRV) during HD, as a surrogate for ANS response to stressors, between the ACE genotypes. In a sample of patients with chronic kidney disease I/D ACE genotypes were assessed with PCR and HRV was measured before, in the second hour, and after a HD session. HRV parameters in the time and frequency domains were analyzed by repeated-measures mixed models according to the time of measurement and ACE polymorphism. HRV parameters in the frequency domain presented significantly different variations during the HD session between patients with or without the D allele. Only patients with the II genotype presented an increase in low-frequency normalized units and in the low frequency-to-high frequency ratio throughout HD. Patients with the II genotype seemed to have a more physiological response to the volemic and electrolytic changes that occur during HD, with greater sympathetic activation than patients with ID and DD genotypes. NEW & NOTEWORTHY Adding to the effort to understand the complexity of cardiovascular system regulation, we have found that the autonomic nervous system response to the acute volume removal during hemodialysis may be different between angiotensin-converting enzyme insertion/deletion polymorphisms. To our knowledge, this is the first time that this specific interaction was analyzed during a volume removal intervention.
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High-molecular-weight adiponectin is inversely associated with sympathetic activity in polycystic ovary syndrome.
Shorakae, S, Abell, SK, Hiam, DS, Lambert, EA, Eikelis, N, Jona, E, Sari, CI, Stepto, NK, Lambert, GW, de Courten, B, et al
Fertility and sterility. 2018;(3):532-539
Abstract
OBJECTIVE To examine the role of high-molecular-weight (HMW) adiponectin and its relationship to sympathetic activity in women with polycystic ovary syndrome (PCOS). DESIGN Cross sectional study using biobanked samples. SETTING Not applicable. PATIENT(S): Premenopausal women with PCOS (n = 46, Rotterdam diagnostic criteria) and without PCOS (n = 22). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): High-molecular-weight adiponectin levels with secondary outcomes of sympathetic activity and leptin levels. RESULT(S): The high-molecular-weight adiponectin level was lower in women with PCOS (median 2.2 [interquartile range (IQR)2.3] μg/mL) than in controls (median 3 [IQR2.5] μg/mL) (age and BMI adjusted), and it correlated inversely with the values measured for homeostatic model of assessment of insulin resistance (HOMA-IR), fasting insulin, triglycerides, and free androgen index and positively with sex hormone-binding globulin (SHBG) and high-density lipoprotein cholesterol in all participants and in the PCOS group. In the PCOS group, sympathetic activity (burst frequency) was statistically significantly higher than in controls (median 26 [IQR11] vs. median 22 [IQR14], respectively) and correlated inversely with HMW adiponectin (r = -0.230). The leptin levels were similar between the women with PCOS and controls and did not statistically significantly correlate with HMW adiponectin or sympathetic activity. On multiple regression analysis, burst frequency and SHBG explained 40% of the HMW adiponectin variability (B = -0.7; 95% CI -1.2 to -0.2; and B = 0.01; 95% CI 0.004-0.01) in PCOS. CONCLUSION(S): Alongside insulin resistance, increased sympathetic activity is associated with and may modulate HMW adiponectin levels in women with PCOS.
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[Relationship between homocysteinaemia and sympathetic skin response in Parkinson's disease].
Crespo-Burillo, JA, Almarcegui-Lafita, C, Dolz-Zaera, I, Alarcia-Alejos, R, Roche, JC, Ara, JR, Capablo-Liesa, JL
Revista de neurologia. 2017;(8):348-352
Abstract
INTRODUCTION High levels of homocysteine linked to treatment with levodopa have been observed in patients with Parkinsons disease (PD). Our aim was to assess the influence of serum homocysteine levels and other PD-related on the sympathetic skin response. PATIENTS AND METHODS An observational, cross-sectional study was conducted that consecutively included patients with PD. We unilaterally assessed the sympathetic skin response in the upper limbs. We measured the influence of PD severity (measured by the Hoehn and Yahr and the Schwab and England scales, and the Unified Parkinson Disease Rating Scale) and blood homocysteine, vitamin B12 and folic acid levels on the latency and amplitude of the sympathetic skin response. RESULTS A total of 78 patients were enrolled, and all achieved a sympathetic skin response. In the bivariate analysis, latency was significantly correlated with age, age at PD onset and homocysteinaemia levels. The presence of hyper-homocysteinemia was associated with a longer latency. The amplitude was only correlated with the score on the Schwab and England scale. In the multivariate analysis, age was the only variable that showed a significant association with the latency duration and homocysteine levels. CONCLUSION A direct association could not be established between the increase in homocysteinaemia levels and sympathetic skin response dysfunction in PD. The results of the multivariate analysis suggest that latency prolongation in elderly patients could be due to the fact that these patients have higher blood levels of homocysteinaemia.
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First bite syndrome - An 11-year experience.
Avinçsal, MÖ, Hiroshima, Y, Shinomiya, H, Shinomiya, H, Otsuki, N, Nibu, KI
Auris, nasus, larynx. 2017;(3):302-305
Abstract
OBJECTIVE First bite syndrome is the development of pain in the ipsilateral parotid region after the first few bites of food and can be seen after surgery of the upper cervical region. The aim of this study is to highlight the etiology of this potentially debilitating chronic pain syndrome. MATERIALS AND METHODS Retrospective review of 53 patients undergoing surgery of the upper neck between 2002 and 2013. RESULTS FBS developed in 16 patients (30%). Partial resolution of FBS symptoms occurred in 69% and complete resolution in 12%, whereas 15% had no change. FBS was most common in the patients who had tumor arising from deep lobe of parotid gland in comparison with other sites (50% vs 18%, p=0.017). FBS developed in 57% of patients undergoing external carotid artery (ECA) ligation and in 12.5% of patients in whom ECA was preserved (p=0.0008). Among the patients in whom ECA was preserved, FBS developed in 43% of the patients in whom sympathetic chain was sacrificed and in 4% of the patients in whom sympathetic chain was preserved. CONCLUSION Present results further support the role of sympathetic chain in the development of FBS.
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Favorable effect of sympathetic nervous activity on rehabilitation outcomes in frail elderly.
Shibasaki, K, Ogawa, S, Yamada, S, Iijima, K, Eto, M, Kozaki, K, Toba, K, Ouchi, Y, Akishita, M
Journal of the American Medical Directors Association. 2015;(9):799.e7-799.e12
Abstract
OBJECTIVES Previous studies have suggested the relationship between physical function, mortality, and autonomic nervous activity in frail elderly and that maintaining sympathetic nervous activity might lead to improved physical function and mortality in the elderly population. The aim of this study was to investigate the utility of sympathetic nervous activity measured by heart rate variability in frail elderly patients undergoing inpatient rehabilitation, further focusing the nervous activity on the effect of rehabilitation therapy. DESIGN Prospective cohort study. PARTICIPANTS Sixty-one subjects aged 75 years or older were recruited after treatment of acute phase illness. MEASUREMENTS Before undergoing rehabilitation, data of 24-hour Holter monitoring and a blood venous sample were obtained. From RR intervals in the electrocardiogram, heart rate and SDs of all NN intervals in all 5-minute segments of the entire recording, power spectral density, low frequency (LF), high frequency (HF), and low frequency/high frequency (LF/HF) were calculated. Functional Independence Measure (FIM) and Barthel index were used to measure physical function. RESULTS FIM score and Barthel index were 46.8 ± 25.4 and 32.8 ± 31.7, respectively. Serum total protein, albumin, hemoglobin, and total cholesterol were all significantly related to FIM score and Barthel index before rehabilitation. Heart rate variability indices did not show a significant relationship with physical function, whereas the high LH/HF group showed significant improvement in physical function compared with the low LH/HF group. Moreover, LF/HF frequency was a predictive factor for improvement of physical function after 2 months of rehabilitation. CONCLUSION A favorable effect of preserved LF/HF on rehabilitation outcome was observed in elderly undergoing rehabilitation. Preservation of sympathetic nervous activity may lead to improved physical function in the elderly.