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Aims To examine whether acute changes in patient hydration can change atrial contribution (AC) to circulatory function. [ABSTRACT FROM PUBLISHER]

In fever, as in normal thermoregulation, signals from the preoptic area drive both cutaneous vasoconstriction and thermogenesis by brown adipose tissue (BAT). Both of these responses are mediated by sympathetic nerves whose premotor neurons are located in the medullary raphé. EP3 receptors, key prostaglandin E2 (PGE2) receptors responsible for fever induction, are expressed in this same medullary raph6 region. To investigate whether PGE2 in the medullary raph6 might contribute to the febrile response, we tested whether direct injections of PGE2 into the medullary raph6 could drive sympathetic nerve activity (SNA) to BAT and cutaneous (tail) vessels in anesthetized rats. Microinjections of glutamate (50 mM, 60–180 nl) into the medullary raphé activated both tail and BAT SNA, as did cooling the trunk skin. PGE2 injections (150–500 ng in 300–1,000 nl) into the medullary raphé had no effect on tail SNA, BAT SNA, body temperature, or heart rate. By contrast, 150 ng PGE2 injected into the preoptic area caused large increases in both tail and BAT SNA (+60 ± 17 spikes/15 s and 1,591 ± 150% of control, respectively), increased body temperature (+1.8 ± 0.2°C), blood pressure (+17 ± 2 mmHg), and heart rate (+124 ± 19 beats/min). These results suggest that despite expression of EP3 receptors, neurons in the medullary raph6 are unable to drive febrile responses of tail and BAT SNA independently of the preoptic area. Rather, they appear merely to transmit signals for heat production and heat conservation originating from the preoptic area. [ABSTRACT FROM AUTHOR]

Background: There are a few studies showing no significant heart rate variability (HRV) over a 24-hour period in vasovagal syncope (VVS) patients, but no research has examined HRV and its sympathetic and parasympathetic components during rapid eye movement (REM) and non-REM sleep. The authors hypothesized that REM sleep might be a critical state in which VVS patients would show abnormal responses. Objectives: To analyze the sympathetic and parasympathetic components of HRV during REM and SWS in patients with VVS compared to normal subjects, and in patients with positive HUTT compared to negative ones. Methods: Thirty-seven VVS patients and 20 normal age-matched controls were submitted to polysomnography with 24-hour Holter monitoring to assess HRV. Time and frequency domain techniques were carefully performed for 24 hours and during Stages 3 and 4 of REM and non-REM sleep. Variation of sympathetic activity index (VSAI) was defined as the difference in the low frequency (LF) component of HRV between REM and Stages 3 and 4 of non-REM sleep. An analysis of variance was performed to compare patients and controls; patients with positive and negative head-up tilt testing. Results: The LF component was lower in syncope compared to normal patients (1,769.54 ± 1,738.17, 3,225.37 ± 2,585.05, respectively, P = 0.03). There was a significant decrease in VSAI in the syncope group compared to the control group (−539.39 ± 1,930.78, 1,268.10 ± 2,420.20, respectively, P = 0.01). The other sleep variables analyzed including very LF, high frequency, low frequency/high frequency and time domain parameters did not reach statistical significance. Syncope patients also showed an increase in slow wave sleep (28.2 ± 10.5, 19.7 ± 7.8, P = 0.01). Conclusions: VVS patients exhibited sympathetic suppression during REM sleep. Possible mechanisms are discussed in this article. [ABSTRACT FROM AUTHOR]

Background: This study compares the effects of telmisartan hydrochlorothiazide (HCTZ) combination versus nifedipine GITS on ambulatory blood pressure (BP) and sympathetic activity, in patients with mild-to-moderate hypertension. Methods: One hundred twenty-four outpatients with sitting diastolic BP ≥95 mm Hg and <110 mm Hg were randomized to telmisartan 80 mg/HCTZ 12.5 mg daily (n = 62) or nifedipine GITS 60 mg daily (n = 62) for 12 weeks, according to a prospective, open-label, blind end point, parallel-group design. At the end of a 2-week washout period and after 12 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed, clinic BP and heart rate were measured, and plasma norepinephrine and cardiovascular responses to mental stress induced by the color word test were assessed. Results: Both treatments reduced ambulatory and clinic BP. However, the drug combination had an antihypertensive efficacy significantly greater than nifedipine GITS, as shown by the 24-h (P < .001), daytime (P < .001), and night-time (P < .01) ambulatory BP monitoring values, as well as by the clinic BP at trough (P < .05).The trough-to-peak ratio was similar, but the smoothness index was significantly higher with the combination for both systolic and diastolic BP (P < .05). A significant increase in plasma norepinephrine levels in resting conditions was observed with nifedipine GITS (+20%) but not with telmisartan/HCTZ combination. The color word test produced a greater increase in plasma norepinephrine and heart rate values in the patients treated with nifedipine GITS than in those treated with the combination. Conclusions: These results suggest that the telmisartan 80 mg/HCTZ 12.5 mg combination provided a more sustained and homogeneous BP control than nifedipine GITS 60 mg, without producing sympathetic activation. [Copyright &y& Elsevier]

We ran two experiments to investigate whether peripheral arterial tone reflects changes in mental effort. Finger pulse wave amplitude, interpulse interval, and pulse variability in the mid- and high-frequency bands were recorded by means of a newly developed finger plethysmograph during both rest and cognitive performance. Using a modified version of the Sternberg memory task, we selectively manipulated either the difficulty of the task (Experiment 1) or the subjects' level of engagement in the task (Experiment 2). We found a significant difference in finger pulse wave amplitude between rest and task periods, suggesting that the measure reflects changes in sympathetic activity due to task engagement. In addition, our results suggest that reduced pulse wave amplitude, signaling vasoconstriction, occurs when subjects are investing effort. [ABSTRACT FROM AUTHOR]

Aims To evaluate the presence of an abnormal autonomic modulation before, during and immediately after paroxysmal atrial fibrillation (PAF). [ABSTRACT FROM PUBLISHER]

Purpose. – This article is an update of past and current data on the relationship between obstructive sleep apnea syndrome and cardiovascular diseases.Current knowledge and key points. – Obstructive sleep apnea syndrome is a common, but under-recognised, condition and should not be considered simplistically as the association of snoring and obesity. It may be suspected by the clinical history but a definite diagnosis requires the practice of polysomnography. Numerous studies have found a significant relationship between the presence of obstructive sleep apnea syndrome and the occurrence of cardiovascular events. Nonetheless, a definite causal relationship has only been established for the occurrence of hypertension. There are multiple immediate and delayed cardiovascular responses to the apneic events and thus there are many possible physiopathological mechanisms to explain the association of obstructive sleep apnea and cardiac and vascular events, the primary one being sympathetic hyperactivity. The prognosis of obstructive sleep apnea syndrome is closely related to the incidence of cardiovascular events.Future prospects and projects. – The existence of an independent relationship between obstructive sleep apnea syndrome and atherosclerosis is not yet demonstrated. The beneficial effects of continuous positive airway pressure, the treatment of choice for this condition, on the incidence of cardiovascular diseases remains to be confirmed although recent studies suggest that correct treatment of obstructive sleep apnea syndrome by continuous positive airway pressure may reduce the cardiovascular risk and in particular that of hypertension. [Copyright &y& Elsevier]

Objectives and background: Arousals from sleep are associated with increased sympathetic activation and therefore with peripheral vasoconstriction. Sleep fragmentation in the form of multiple arousals is associated with daytime somnolence and cognitive impairment; however, manual scoring of arousal is time consuming and problematic due to relatively high inter-scorer variability. We have recently shown that automated analysis of in-lab recorded peripheral arterial tone (PAT) signal and the pulse rate derived from it can accurately assess arousals from sleep as defined by the American Academy of Sleep Medicine (AASM). In the current study we sought to extend these findings to the Watch_PAT100 (WP100), an ambulatory device measuring PAT, oximetry and actigraphy.Methods: Sixty-eight subjects (61 patients referred to the sleep lab with suspected obstructive sleep apnea and seven healthy volunteers, mean age 46.3±14.2 years) underwent a whole night polysomnography (PSG) with simultaneous recording of PAT signal by the ambulatory WP100 device. The PSG recordings were blindly manually analyzed for arousals based on AASM criteria, while PAT was scored automatically based on the algorithm developed previously.Results: There was a significant correlation between AASM arousals derived from the PSG and PAT autonomic arousals derived from the WP100 (R=0.87, P<0.001), with a good agreement across a wide range of values. The sensitivity and specificity of PAT in detecting patients with at least 20 arousals per hour of sleep were 0.80 and 0.79, respectively, with a receiver operating characteristic curve having an area under the curve of 0.87.Conclusions: We conclude that automatic analysis of peripheral arterial tonometry signal derived from the ambulatory device Watch_PAT100 can accurately identify arousals from sleep in a simple and time saving fashion. [Copyright &y& Elsevier]

In human beings, cardiovascular activity has a distinct circadian variation: Heart rate, blood pressure, and vascular tone decrease at night. Nocturnal cardiovascular blunting is at least partially linked to the autonomic activity and increased risk of cardiac and cerebral events. To assess whether decreased nocturnal melatonin synthesis and secretion in coronary artery disease (CAD), we investigated nocturnal secretion pattern of melatonin in patients with CAD and healthy subjects. The present study performed in 16 patients with angiographically documented CAD (aged 46–71 years) and in nine healthy controls (aged 36–66 years). Blood samples were collected every 2 h between 22:00 and 08:00 h. Melatonin levels were measured with a commercially available radioimmunoassay kit. We found large interindividual variation in the pattern of melatonin secretion in both groups. Patients with CAD secreted less nocturnal melatonin at 02:00, 04:00 and 08:00 h than control subjects (P=0.014, P=0.04 and P=0.025, respectively). Peak and Δ melatonin (peak–lowest melatonin) were found lower in patients with CAD (48.6 [19.1–75.4] vs. 131.4 [67.8–137.2] pg/ml, P=0.006 and 43 [10.5–68.5] vs. 107.6 [55.7–113.1] pg/ml, P=0.002, respectively). Peak time of melatonin secretion was observed earlier in patients with CAD (02:00 h [23:00–02:00 h] vs. 03:45 h [02:00–05:00 h], P=0.04). Our study provides useful and preliminary information about decreased nocturnal melatonin synthesis and release in patients with CAD might help physicians in managing these patients. [Copyright &y& Elsevier]

Background: We previously reported that increased peak serum C-reactive protein (CRP) level after acute myocardial infarction (AMI) was a major predictor of cardiac rupture and long-term outcome. The aim of this study was to clarify the role of serum CRP elevation as a possible marker of left ventricular (LV) remodeling after AMI. Methods: We prospectively studied 31 patients who underwent primary angioplasty for a first anterior Q-wave AMI. Peak serum CRP level was determined by serial measurements after admission. LV volume and the plasma levels of various neurohormones and cytokines were measured on admission, and 2 weeks and 6 months after AMI. Results: Patients with higher peak CRP levels (above the median) had a greater increase in LV end-diastolic volume during 2 weeks after AMI (+21±14 vs. +5±6 ml/m2, P=0.001) and a lower ejection fraction (45±11 vs. 53±7%, P=0.02) than those with lower CRP levels, associated with a higher incidence of pump failure, atrial fibrillation, and LV aneurysm. Plasma levels of norepinephrine, brain natriuretic peptide, and interleukin-6 2 weeks after AMI were higher in the high CRP group than in the low CRP group. Conclusions: Increased peak serum CRP level was associated with a greater increase in LV volume after anterior AMI. Plasma norepinephrine and interleukin-6 levels were increased in patients with higher CRP levels, suggesting a possible role of sympathetic activation and enhanced immune response in the development of LV remodeling after AMI. [Copyright &y& Elsevier]

Introduction: Salt restriction results in endogenous sympathetic activation, and we previously showed that plasma concentrations of quinidine measured after oral drug administration are increased during a low-salt diet. However, it is not known whether, independent of effects on plasma concentration, the extent to which quinidine prolongs the QT interval also is modulated by changes in endogenous sympathetic activity. Methods and Results: In these studies, we evaluated quinidine concentration-QT relations during low-salt (10 mEq/day for 8 days) and high-salt (400 mEq/day for 8 days) diets, with or without beta blockade in normal volunteers. In the absence of beta blockade, the concentration producing a fixed (15%) increase in QTc was significantly lower with salt restriction: 1.2 ± 0.4 µg/mL (low salt) versus 2.2 ± 0.4 µg/mh (high salt) (P < 0.01). With beta blockade, this difference was abolished: 1.9 ± 0.3 µg/mL (low salt + beta blockade) versus 2.1 ± 0.3 µg/mL (high salt + beta blockade). QT morphologic abnormalities including bifid T waves and U waves were abolished with beta-adrenergic blockade. Conclusion: Sympathetic activation by a low-salt diet not only modulates drug disposition but also increases sensitivity to drug-induced QT prolongation. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Patients with Type I (insulin-dependent) diabetes mellitus have a reduced transcapillary fluid absorption from skeletal muscle and skin and thus defective plasma volume regulation during hypovolaemia. Our aim was to find whether a defective capillary filtration coefficient or impaired transcapillary driving force are aetiologic factors for this reduction. Methods. We investigated 11 diabetic patients (diabetes duration 6.9 ± 1.1 years, age 26 ± 1 years), without complications and 12 control subjects (26 ± 1 years). Their capillary filtration coefficient was measured in the upper arm using a volumetric technique at rest and during lower body negative pressure (LBNP). We calculated the driving force for transcapillary fluid transfer. Results. The increase in heart rate and the decrease in systolic blood pressure during lower body negative pressure were similar in diabetic and control subjects. The resting capillary filtration coefficient was decreased in the diabetic subjects, 0.033 ± 0.003 vs 0.051 ± 0.007 ml · 100 ml–1· min–1· mmHg–1 (p < 0.05). During lower body negative pressure, the capillary filtration coefficient increased 35 % in both groups compared with resting capillary filtration coefficient and was still decreased in diabetes; 0.046 ± 0.004 compared with 0.069 ± 0.006 ml · 100ml–1· min–1· mmHg–1 (p < 0.01). The established driving force during lower body negative pressure was 1.37 ± 0.11 vs 1.30 ± 0.15 mmHg (NS) in diabetic and control subjects, respectively. Conclusions/interpretation. Our study indicates that a reduced capillary filtration coefficient rather than defective regulation of transcapillary driving force, is the reason for the reduced transcapillary fluid absorption during hypovolaemic circulatory stress found in Type I diabetic patients. [Diabetologia (2000) 43: 1178–1184] [ABSTRACT FROM AUTHOR]

The accumulating literature linking stress with negative health outcomes, including cardiovascular disease (CVD), is extensively reported yet poorly defined. Stress is associated with a higher risk of hypertension, acute myocardial infarction, arrhythmogenesis, and heart failure. Stress mediates its effect through direct neuronal, endocrine, autonomic, and immune processes and indirectly by modifying lifestyle behaviors that promote CVD progression. Stress occurs when an individual perceives that internal or external demands exceed the capacity for an adaptive response. Psychologic stress is increasingly recognized in the atrial fibrillation (AF) population, although the pathophysiology remains unclear. There appears to be a bidirectional relationship between AF and stress with a complex interplay between the 2 entities. Stress modulates the immune and autonomic nervous systems, key drivers in AF initiation and potentiation. AF leads to increasing anxiety, psychologic distress, and suicidal ideation. Recently, lifestyle modification has emerged as the fourth pillar of AF management, with stress reduction a potential reversible risk factor and future target for intervention. This review examines proposed mechanisms linking AF and stress and explores stress reduction as an adjunct to the AF management armamentarium., Competing Interests: Funding Support and Author Disclosures Dr Segan is supported by a NHMRC/NHF co-funded postgraduate scholarship. Prof Kalman is the recipient of a Practitioner Fellowship of the NHMRC and has received research and fellowship support from Medtronic, Abbott, Itamar Medical, and Biosense Webster. Prof Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr Prabhu has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this work was to relate the activation of the sympathetic and parasympathetic nervous systems with the skin temperature (Tsk) of the lower limbs after a resistance training exercise. Under controlled conditions, the average Tsk in the areas of the anterior and posterior thighs, knees and legs was obtained with a thermal imager and the parasympathetic and sympathetic activation was registered with an Omegawave® device on 20 healthy and trained male volunteers (25.39 ± 8.21 years) before exercise, immediately after standard resistance training (3 exercises (2 quadriceps + 1 hamstrings) × 4 sets × 10 repetitions (70% 1RM), 90-sec recovery) and after 20 min of recovery. The results showed a significant effect of exercise and recovery on Tsk in all regions of interest (ROIs) considered (p < 0.05) and strong inverse relationships between sympathetic and parasympathetic activation values. Significant results were found for the total variation of Tsk (p < 0.05) with highly positive values for subjects with lower sympathetic activation and almost null or even negative values for those with higher sympathetic activation. Sympathetic activity was a significant predictor of total Tsk variation in the anterior thigh, posterior thigh and anterior knee but not in the posterior knee, anterior leg, and posterior leg. Baseline Tsk was a significant predictor of total Tsk variation the all ROIs except in the posterior knee. Tsk measured by thermography could be used to estimate the level of participation of muscle areas in exercise and registering the level of sympathetic activation before exercise could be interesting in predicting the athlete's physiological response to strength training. [ABSTRACT FROM AUTHOR]

• Relations between acute stress and WM function in youth were examined. • Two stress systems were examined for their individual and joint contributions. • Associations between arousal and WM differed for the inhibitory control facet of WM. • Enhancement and impairment of WM emerged as a function of arousal and development. Despite considerable research with adults suggesting that acute stress negatively affects working memory (WM), a core cognitive function, few studies have assessed these effects in youths. Studies that have been conducted have produced null findings, although these studies did not measure stress via multiple systems (e.g., hypothalamic–pituitary–adrenal [HPA] axis and sympathetic nervous system [SNS]) or include wide developmental age ranges. In the current study, we examined the links between acute stress and WM in 8- to 15-year-olds. Youths completed the Trier Social Stress Test–Modified, during which repeated saliva samples were collected to measure responses of the HPA axis (cortisol) and SNS (salivary alpha-amylase). Immediately afterward, youths completed the n -back task, an established measure of WM. Accuracy and false alarm (FA) scores were computed to explore whether associations between arousal and WM differed when WM versus only the inhibitory control facet of WM processes were considered. Relations varied as a function of age, physiological system, and type of WM process. Accuracy improved and FA scores deceased as age and SNS reactivity increased, particularly in combination. Moreover, when arousal was higher according to only one physiological system (HPA axis or SNS), FA scores were lower, but when arousal was driven by both systems or low in both systems, FA scores were higher. Together, results highlight the need for more complex investigations of stress and WM across development that take into account system-specific responses and multiple facets of WM. [ABSTRACT FROM AUTHOR]

Background Cigarette smoking accelerates progression of renal failure in diabetic and nondiabetic renal disease. Renal hemodynamics during smoking are characterised by a reversible decrease in glomerular filtration rate (GFR) and filtration fraction (FF) accompanied by increased renovascular resistance (RVR), systemic blood pressure, heart rate and plasma catecholamine concentrations. Materials and methods To further assess the role of sympathetic overactivity we compared the effects of different pharmacological interventions on smoking-induced changes of renal hemodynamics in occasional smokers. In a first series, placebo pretreatment plus smoking was compared to Prazosin pretreatment (3 mg) plus smoking. In a second study, placebo pretreatment plus smoking was compared to Atenolol pretreatment (50 mg) plus smoking. Results Basal blood pressure was significantly lower with Prazosin and Atenolol. On placebo, GFR and FF decreased significantly during smoking and RVR increased. With Prazosin pretreatment compared to placebo pretreatment no statistically significant differences for the changes of GFR, FF, RPF and RVR were seen. In contrast, with Atenolol pretreatment compared to placebo pretreatment, the smoking-induced changes in active renin, GFR and RVR were significantly smaller. Conclusion It is suggested that the acute renal hemodynamic effects of smoking are mediated, at least in part, via increased sympathetic activity operating mainly through beta-1 adrenergic mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes mellitus is associated with a high cardiovascular morbidity which has been linked to disturbances in microvascular function. This study was designed to examine the transcapillary fluid absorption during experimental hypovolaemia in type 1 diabetes.Subjects: Twelve males with type 1 diabetes (age 25 +/- 3 years, duration 8 +/- 1 years) with no clinical microangiopathy and 12 healthy males (22 +/- 2 years).Interventions: As a model for hypovolaemic circulatory stress, lower body negative pressure (LBNP: 15, 30 and 60 cmH2O) was used. Transcapillary fluid absorption from tissue to blood in the upper arm, as well as forearm blood flow, was measured by volumetric technique.Results: Resting forearm blood flow, heart rate and blood pressure were similar in diabetic patients and controls. Basal plasma noradrenaline was reduced in the diabetics compared with controls (0.75 +/- 0.06 vs. 1.09 +/- 0.10 pmol L-1, P < 0.05), but the increase in plasma noradrenaline in response to LBNP was similar in the two groups. The haemodynamic responses to LBNP in the two groups were equal, showing a reduction of pulse pressure, an increase in heart rate and in peripheral resistance with a concomitant blood flow reduction. The transcapillary fluid absorption (mL 100 mL-1 min-1) was significantly reduced in the diabetic patients: LBNP 15 cmH2O, 0.024 +/- 0.004 vs. 0.036 +/- 0. 002; 30 cmH2O, 0.041 +/- 0.003 vs. 0.056 +/- 0.005; and 60 cmH2O, 0. 057 +/- 0.007 vs. 0.091 +/- 0.008 (diabetic patients vs. controls, P < 0.001).Conclusions: The transcapillary fluid absorption from tissue to blood during hypovolaemic circulatory stress in type 1 diabetic patients is reduced by one-third compared with controls, which indicates impaired plasma volume regulation. This basic mechanism for plasma volume control is affected before clinical microcirculatory complications are found and could be one of the causes of the increased cardiovascular morbidity and mortality in IDDM. [ABSTRACT FROM AUTHOR]

Using delayed auditory feedback (delay 0.175 s) a standardized form of mental stress was investigated in 8 healthy male volunteers. After a resting period and a period of undelayed reading, the volunteers were exposed for 5 min to the DAF stress. During the DAF period heart rate increased by 10% and systolic and diastolic blood pressure increased by 9% and 18%, respectively. As a measure of acute sympathetic activation, plasma concentrations of norepinephrine and epinephrine rose by 68% and 49%, respectively. The activity of dopamine-β-hydroxylase in plasma was increased by 25%. From these results it can be concluded that the DAF procedure provides a suitable method for inducing a standardized mental stress in normal subjects, which can be measured as changes in biochemical and cardiovascular variables. [ABSTRACT FROM AUTHOR]

A strong sympathetic activation has been observed in heart failure and is the cause of β-adrenergic desensitization in this condition. On the receptor level there is downregulation of β1-adrenergic receptors and uncoupling of β2-adrenoceptors. The latter mechanism has been related to an increased activity and gene expression of β-adrenoceptor kinase in failing myocardium, leading to phosphorylation and uncoupling of receptors. β3-Adrenoceptors mediate negative inotropic effects, but alterations in these receptors are not known. In addition, an increase in inhibitory G protein α subunits (Giα) has been suggested to be causally linked to adenylyl cyclase desensitization in heart failure. In contrast, the catalytic subunit of adenylyl cyclase, stimulatory G protein α and βγ subunits, have been observed to be unchanged. Recent evidence shows that increases in Giα also depress adenylyl cyclase in compensated cardiac hypertrophy both in monogenic and polygenic and in secondary hypertension. These increases of Giα can suppress adenylyl cyclase in the absence of β-adrenergic receptor downregulation. Since cardiac hypertrophy in pressure overload is a strong predictor of cardiac failure, these observations indicate that adenylyl cyclase desensitization by Giα may be a pathophysiologically relevant mechanism contributing to the progression from compensated cardiac hypertrophy to heart failure. [ABSTRACT FROM AUTHOR]

Introduction: Tilt table testing is widely used in the management of patients with neurocardiogenic syncope. However, the exact pathophysiologic mechanism of this disorder is still under debate. Likewise, therapy of these patients continues to represent a challenge in many cases. Therefore, the present study aimed to gain further insight into the pathophysiology of this syndrome and to examine easily accessible clinical parameters that can improve therapy selection. Methods and Results: In 16 patients with neurocardiogenic syncope, changes in endogenous catecholamine concentrations were determined during repeated tilt table testing before and during treatment with metoprolol. Tachycardia preceded .syncope in 8 of 10 responders compared to only 1 of 6 nonresponders (P < 0.05). In responders, the relative increase in epinephrine levels averaged 197% ± 51% during drug-free tilting and 75% ± 33% during repeated testing while on β-blocker therapy (P < 0.05). In nonresponders, there was a smaller relative increase in epinephrine averaging 137% ± 35% at baseline tilt. During repeated tilt testing, a similar increase was observed in these patients with recurrent syncope (156% ± 104%; P = NS compared to baseline). Conclusion: In patients with neurocardiogenic syncope who show both an increase in epinephrine concentration during tilt test and sinus tachycardia prior to the onset of symptoms, β-blocker treatment is very effective. These findings confirm the major role of sympathetic activation as a trigger of syncope. Particularly, heart rate changes at the onset of syncope may allow early identification of patients responding to antiadrenergic therapy. [ABSTRACT FROM AUTHOR]

ACE inhibitors have the potential to affect myocardial ischaemia in patients with asymptomatic ventricular dysfunction and ischaemic cardiomyopathy after long-term treatment. However, anti-ischaemic effects are virtually absent in stable effort angina during short-term therapy, which suggests different mechanisms of action in different patient subtypes. Long-term treatment in left ventricular dysfunction may lead to a reduction in myocardial oxygen demand and ischaemia as a result of ventricular remodelling, possibly supported by structural coronary vascular effects i e. an improved endothelial function and vasodilator capacity. An alternative mechanism by which ACE inhibitors may affect ischaemia, is through modulation of ischaemia-induced neurohormonal activation and subsequent systemic vasoconstriction. Depending on the severity of ischaemia, pronounced catecholamine activation and stimulation of the circulating renin-angiotensin system occur, accompanied by systemic vasoconstriction and an increase in afterload. These changes are marked in patients with left ventricular dysfunction. Moreover, a change from net catecholamine release to uptake in the ischaemic area is observed. Although the clinical significance of the latter observation is still unclear sympathetic activation may lead to coronary vasoconstriction in stenotic areas where normal endothelium-dependent coronary vasodilatation has become impaired. In the resting patient, enalaprilat and perindoprilat significantly reduce myocardial ischaemia, not by a direct effect on the oxygen supply-demand ratio, but through modulation of neurohormonal activation, in particular of sympathetic activation during ischaemia, and, subsequently, by preventing systemic vasoconstriction. These effects are pronounced in left ventricular dysfunction, at least where perindoprilat is concerned. The possibility that ACE inhibitors improve endothelialfunction in concert with their modulating effects on ischaemia-induced neurohormonal activation and hence influence the occurrence of myocardial ischaemia during long-term treatment needs further evaluation. [ABSTRACT FROM PUBLISHER]

To assess whether the presence of areas of efferent sympathetic denervation might contribute to alterations in sympathetic and vagal neural regulatory activities observed after myocardial infarction, we attempted to correlate the changes in the spectral components ofRR variability with the 1–123 MIBG and Thallium-201 uptake defects. Ten patients with first and uncomplicated myocardial infarction were studied. Thallium-201 and 1–123 MIBG scintigraphy as well as spectral analysis of heart rate variability were performed 7 days, 4, 12 and 30 months after the acute event. Regional abnormalities in 1–123 MIBG uptake were more extensive than the perfusion defects indicated by Thallium-201 images and remained constant throughout the entire period of observation. In the early post-infarction period, spectral analysis of RR variability was characterized by a predominant LF (74±6nu) and a smaller HF (16±3nu) component indicating a sympathetic predominance. Thereafter, we observed a progressive reduction in LF and a gradual increase in HF which were consistent with a normalization of sympatho-vagal balance. These data indicate that after a myocardial infarction, the presence and persistence of areas of sympathetic functional denervation do not seem to play a major role in determining the changes in sympathetic and vagal neural regulatory activities directed to the heart. [ABSTRACT FROM PUBLISHER]

To determine whether enhanced sympathetic activity could alter a non-invasive index of cardiac instability, we analysed the effects of 90° head-up tilt and submaximal exercise stress test on high amplification signal-averaged electrocardiogram in 64 patients after acute myocardial infarction. At rest, ventricular late potentials were detected in 25% of patients, characterized by a significant prolongation of filtered QRS complex (137 ±3 vs 115 ±2 ms) and of its components smaller than 40 fiV (38 ±2 vs 16 ±1 ms), as well as by a reduced root mean square voltage calculated for the terminal 40 ms of QRS complex (RMS40 voltage) (19 ± 1 vs 75 ± 9μV) in comparison to patients without micropotentials. Sympathetic activation induced by tilt caused a significant increase in heart rate (from 67 ±3 to 79 ±3 beats min) but did not modify either the incidence of ventricular late potentials or the values of any of the signal-averaged electrocardiogram parameters considered. In 19 patients, recordings were also obtained during a submaximal bicycle exercise stress test at a heart rate of 114 ±4 beats min and with systolic arterial blood pressure at 153 ±6 mmHg. No effect on signal-averaged electrocardiogram parameters was detectable during this experimental intervention. These data indicate that after myocardial infarction, sympathetic activation does not seem to modify signal-averaged electrocardiogram parameters. [ABSTRACT FROM PUBLISHER]

To evaluate the possible influence of sympathetic activation on the haemodynamic response to intravenous beta-blockade, the dose-response characteristics of three boluses of propranolol were evaluated in 8 patients with uncomplicated infarction and compared in a similar number of patients with stable angina. Following a control period, when haemodynamic stability was confirmed, propranolol 2, 2 and 4 mg (cumulative dosage 2, 4 and 8 mg) was injected into the central circulation at 15 min intervals. Despite close matching in baseline control haemodynamic variables between the groups, in stable angina, pro pranolol resulted in dose-related depression of cardiac output without change in systemic blood pressure, whereas following myocardial infarction the drug induced significantly greater falls in cardiac output (P>0-05) and a dose-related decrease in systemic blood pressure. Despite the greater effects of propranolol on cardiac output following myocardial infarction, the left ventricular filling pressure was increased to a lesser extent compared with stable angina. The explanation for this observation may reside in a greater susceptibility of the left ventricular wall to increase its compliance, under conditions of high sympathetic stimulation, following beta-blockade. These data support experimental and biochemical evidence of sym pathetic activation in myocardial infarction; the hyperadrenergic state conditions an augmented haemody namic response to competitive antagonism of sympathetic stimulation at cardiac beta-adrenocep tors. [ABSTRACT FROM PUBLISHER]

Obstructive sleep apnea (OSA) is characterized by upper airway collapse during sleep. Chronic intermittent hypoxia, sleep fragmentation, and inflammatory activation are the main pathophysiological mechanisms of OSA. OSA is highly prevalent in obese patients and may contribute to cardiometabolic risk by exerting detrimental effects on adipose tissue metabolism and potentiating the adipose tissue dysfunction typically found in obesity. This chapter will provide an update on: (a) the epidemiological studies linking obesity and OSA; (b) the studies exploring the effects of intermittent hypoxia and sleep fragmentation on the adipose tissue; (c) the effects of OSA treatment with continuous positive airway pressure (CPAP) on metabolic derangements; and (d) current research on new anti-diabetic drugs that could be useful in the treatment of obese OSA patients., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Obstructive sleep apnea (OSA), the most common form of sleep-disordered breathing, is characterized by repetitive episodes of paused breathing during sleep, which in turn induces transient nocturnal hypoxia and hypercapnia. The high prevalence of OSA and its associated health consequences place a heavy burden on the healthcare system. In particular, the consequent episodic oxygenic desaturation/reoxygenation series and arousals from sleep in patients with OSA have the potential to trigger oxidative stress, elevated systemic inflammatory responses, and autonomic dysfunction with sympathetic activation. Given these adverse side-effects, OSA is highly correlated to many eye diseases that are common in everyday ophthalmic practices. Some of these ocular consequences are reversible, but they may permanently threaten a patient's vision if not treated appropriately. Here, this article seeks to review the ocular consequences and potential pathophysiologic associations in patients with OSA. Understanding these OSA-related eye diseases may help clinicians provide comprehensive care to their patients. [ABSTRACT FROM AUTHOR]

Background: Sham-controlled trials demonstrated safety and efficacy of renal denervation (RDN) to lower blood pressure (BP). Association of baseline heart rate with BP reduction after RDN is incompletely understood., Objectives: The purpose of this analysis was to evaluate the impact of baseline heart rate on BP reduction without antihypertensive medications in the SPYRAL HTN-OFF MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications) Pivotal trial., Methods: Patients removed from any antihypertensive medications were enrolled with office systolic blood pressure (SBP) ≥150 and <180 mm Hg and randomized 1:1 to RDN or sham control. Patients were separated according to baseline office heart rate <70 or ≥70 beats/min. BP changes from baseline to 3 months between treatment arms were adjusted for baseline SBP using analysis of covariance., Results: Scatter plots of 3-month changes in 24-hour and office SBP illustrate a wide range of changes in SBP for different baseline heart rates. Treatment difference at 3 months between RDN and sham control with baseline office heart rate ≥70 beats/min for 24-hour SBP was -6.2 mm Hg (95% CI: -9.0 to -3.5 mm Hg) (P < 0.001) and for baseline office heart rate <70 beats/min it was -0.1 mm Hg (-3.8 to 3.6 mm Hg) (P = 0.97) with an interaction P value of 0.008. Results were similar for changes in office, daytime, and nighttime SBP at 3 months, with a greater reduction in SBP with baseline office heart rate ≥70 beats/min., Conclusions: Reduction in mean office, 24-hour, daytime, and nighttime SBP for RDN at 3 months was greater with baseline office heart rate ≥70 than <70 beats/min, suggesting an association between baseline heart rate and BP reduction after RDN. (SPYRAL PIVOTAL-SPYRAL HTN-OFF MED Study; NCT02439749)., Competing Interests: Funding Support and Author Disclosures The trial is sponsored by Medtronic and was designed in collaboration with the U.S. Food and Drug Administration by the steering committee and sponsor. Profs Böhm, Ukena, Ewen, and Mahfoud are supported by the Deutsche Forschungsgemeinschaft (SFB TTR219, S-01, M-03, M-05). Prof. Böhm has received consulting fees from Abbott Vascular, Bayer AG, Amgen, AstraZeneca, Servier, Medtronic, Vifor, and Boehringer Ingelheim. Dr Tsioufis has received honoraria for advisory boards and lectures from Medtronic, Servier, Bayer, Menarini, Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer, Pythagoras, Sanofi, and Amgen. Dr Kandzari has received institutional research/grant support from Medtronic CardioVascular and Ablative Solutions; and has received personal consulting honoraria from Medtronic CardioVascular. Prof. Kario has received scientific support and speaker honoraria from Daiichi-Sankyo, Sanwa Chemical, Boehringer Ingelheim, Omron Healthcare, A & D Inc, Fukudadenshi Inc, Medtronic, and ReCor Medical. Prof. Weber has received consulting fees from Medtronic, ReCor, and Ablative Solutions. Prof. Schmieder has received consultant fees from Medtronic and ReCor; and has received grant support from Medtronic, ReCor, and Ablative Solutions. Prof. Townsend has received consultant fees from Medtronic, Axio, and Regeneron. Dr Pocock has received consultant fees from Medtronic. Prof. Weil has received honoraria from Medtronic, Novartis, ReCor, Cardinal Health, Bayer, and AstraZeneca. Mr Fahy is an employee of and shareholder for Medtronic. Prof. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie; and has received scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, and ReCor Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

1. Humans experiencing intermittent hypoxia (IH) owing to recurrent apnoea syndromes exhibit serious cardiovascular morbidity, including high blood pressure, increased sympathetic nerve activity, cardiac arrhythmia and myocardial infarction. Although apnoeas are accompanied by a simultaneous decrease in arterial O2 (hypoxia) and an increase in CO2 (hypercapnia), studies on experimental animals suggest that hypoxia, rather than hypercapnia, is the primary stimulus for developing hypertension and enhanced sympathetic nerve activity. Enhanced hypoxic-sensing ability of the carotid bodies and the ensuing reflex activation of the sympathetic nervous system have been suggested to play a critical role in cardiorespiratory alterations resulting from recurrent apnoeas.2. The purpose of the present review is to highlight recent studies demonstrating the effects of IH on carotid body sensory activity and its consequences on sympathetic activation in a rodent model of chronic IH. Adult rats exposed to chronic IH (15 s of 5% O2 followed by 5 min of 21% O2, nine episodes per h, 8 h/day for 10 days) exhibited selective enhancement of carotid body sensory response to hypoxia. In addition, chronic IH induced a novel form of sensory plasticity in the carotid body, manifested as sensory long-term facilitation (LTF). Functional changes in the carotid body occurred in the absence of morphological changes in the chemoreceptor tissue.3. Acute hypoxia increased expiratory modulated splanchnic nerve activity (SNA) and acute IH-induced LTF in SNA. Hypoxia-induced SNA activation was prevented by bilateral sectioning of the sinus nerves. Rats exposed to chronic IH exhibited enhanced hypoxia-induced sympathetic activation and augmented LTF of the SNA. Bilateral sectioning of the sinus nerves abolished these responses, suggesting chronic IH-induced alterations in carotid body sensitivity contribute to LTF in SNA and the subsequent cardiovascular alterations. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) is estimated to account for 1-3% of all patients presenting with suspected ST-segment elevation myocardial infarction. A sudden surge in sympathetic nervous system is considered the cause of TTS. Nonetheless, no specific recommendations have been provided regarding β-blocking therapy. Apart from specific contra-indications (severe LV dysfunction, hypotension, bradycardia and corrected QT interval >500 ms), treatment with a β-blocker seems reasonable until full recovery of LV ejection fraction, though evidence is limited to a few animal studies, case reports or observational studies. In this review, we will reappraise the rationale for β-blocker therapy in TTS and speculate on the pathophysiologic basis for preferring non-selective agents with vasodilating activity over β 1 -selective drugs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of the left ventricle. Despite the widespread use of β-adrenergic blockade and implantable defibrillators, morbidity and mortality from chronic-phase ventricular tachyarrhythmias remains high, calling for further investigation on the underlying pathophysiology. Histological and functional studies have demonstrated extensive alterations of sympathetic nerve endings at the peri-infarct area and flow-innervation mismatches that create a highly arrhythmogenic milieu. Such accumulated evidence, along with the previously well-documented autonomic dysfunction as an important contributing factor, has stirred intense research interest for pharmacologic and non-pharmacologic neuromodulation in post-infarction heart failure. In this regard, aldosterone inhibitors, sacubitril/valsartan and sodium-glucose cotransporter type 2 inhibitors have shown antiarrhythmic effects. Non-pharmacologic modalities, currently tested in pre-clinical and clinical trials, include transcutaneous vagal stimulation, stellate ganglion modulation and renal sympathetic denervation. In this review, we provide insights on the pathophysiology of ventricular arrhythmogenesis post-myocardial infarction, focusing on sympathetic activation.

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1 β ; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Brognara, Castania, Kanashiro, Dias and Salgado.)

High intensity, low volume inspiratory muscle strength training (IMST) has favorable effects on casual systolic blood pressure and systemic vascular resistance. However, the acute effects of IMST on heart rate (HR), blood pressure (BP), and sympathetic regulation of vascular resistance and the trajectory of post exercise recovery are not known. We recruited 14 young adults (7 women/7 men, age: 22 ± 2 years) to perform a single bout of high intensity IMST (inspiratory resistance set at 75% of maximal inspiratory pressure) importantly, female and male subjects were matched in regard to the target inspiratory pressure and target inspiratory muscle work per breath. We recorded HR, beat-to-beat changes in BP and postganglionic, muscle sympathetic nerve activities (MSNA) continuously throughout baseline, a single bout of IMST (comprising five sets of 6 inspiratory efforts) and in recovery. We show that one bout of IMST does not effect a change in BP, however, it effects a significant increase in HR (68.4 ± 11.7 beats/min versus 85.4 ± 13.6 beats/min; P < 0.001) and a significant decline in MSNA (6.8 ± 1.1 bursts/15 s bin; P < 0.001 versus 3.6 ± 0.6 bursts/15 s bin) relative to baseline. Remarkably, among men MSNA rebounded to baseline levels within the first minute of recovery, however, in women, MSNA suppression persisted for 5 min. We show that in healthy young adults, high intensity, low volume respiratory training results in the acute suppression of MSNA. Importantly, MSNA suppression is of greater magnitude and longer duration in women than in men. NEW & NOTEWORTHY Previous studies show 6 weeks of high intensity, low volume inspiratory muscle strength training (IMST) lowers blood pressure (BP) and systemic vascular resistance in young adults. However, the acute response to IMST is unknown. We characterized BP, heart rate, and sympathetic nervous activity (SNA) in healthy young adults at baseline, during IMST, and in recovery. There was no acute effect of IMST on BP, however, there was significant IMST-related suppression of SNA that was of greater magnitude in women than men.

Background: Sympathetic activation is a primary mechanism mediating increased blood pressure (BP) in obstructive sleep apnea (OSA). However, the relationships between overweight/obesity, sympathetic activation and BP in OSA are not well understood. We hypothesized that increased sympathetic drive is associated with increased BP in normal weight, but not in overweight/obese males with OSA. We therefore examined the effects of body mass index (BMI) on the association between sympathetic activation and BP in males with OSA., Methods: We studied 115 males with OSA recruited consecutively from clinic. Twenty-four-hour urinary norepinephrine was used to assess sympathetic activation. Blood pressure was measured both in the evening and in the morning. Hypertension was defined based on either BP measurements or an existing diagnosis. Linear and logistic regressions were conducted to examine the associations between sympathetic activation and both BP and risk of hypertension., Results: We found 24-hour urinary norepinephrine levels were associated with systolic and diastolic BP (SBP, β=0.157, p=0.082; DBP, β=0.212, p=0.023) and mean arterial pressure (MAP, β=0.198, p=0.032) after adjusting for confounders. Interestingly, these associations were modified by overweight/obesity. After adjusting for confounders, increased 24-hour urinary norepinephrine levels were significantly associated with elevated SBP (β=0.454, p=0.012), DBP (β=0.399, p=0.041), and MAP (β=0.432, p=0.023) in normal weight, but not in overweight/obese patients (all p>0.2). Similar findings were observed in the associations between 24-hour urinary norepinephrine levels and hypertension., Conclusion: Sympathetic activation is associated with elevated BP in normal weight but not in overweight/obese males with OSA, suggesting that BMI may moderate the association between sympathetic activation and BP in males with OSA., Competing Interests: All authors have seen and approved the manuscript. Dr. Somers has served as a consultant for Respicardia, Sleep Number, Baker Tilly and Jazz Pharmaceuticals. Dr Somers also reports grants from NIH, outside of the submitted work. Drs. Li, Chen and Tang have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in the article. The authors report no other conflicts of interest in this work., (© 2021 Chen et al.)