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Five-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to hyperbaric oxygenation with an enhanced atmospheric pressure (950 mmHg) and an increased oxygen concentration (36%) for 6 h per day. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored for 8 weeks of hyperbaric oxygenation period. After 8 weeks of hyperbaric oxygenation, the derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potentials (BAPs) were measured. After 5 weeks of hyperbaric oxygenation, the hyperbaric group of WKY exhibited lower SBP than the age-matched normobaric group, while there were no differences in the DBP between the normobaric and hyperbaric groups. After 3 and 7 weeks of hyperbaric oxygenation, the hyperbaric group of SHR exhibited lower SBP and DBP than the age-matched normobaric group. The hyperbaric groups of both WKY and SHR exhibited lower dROMs than the respective normobaric groups. There were no differences in BAPs between the normobaric and hyperbaric groups of WKY. In contrast, the hyperbaric group of SHR exhibited higher BAPs than the normobaric group. We conclude that the hyperbaric oxygenation conditions used in this study effectively repress hypertension. [ABSTRACT FROM AUTHOR]

Background: Pathologists examining victims of sudden unexpected death encounter alcoholics more often than expected; alcohol may play a role in sudden arrhythmic death. Here we determine whether a pattern of alcohol consumption, chronic ethanol intake, and withdrawal increases the incidence of malignant ventricular arrhythmia and modulates susceptibility to the arrhythmogenic potential of sympathetic stimulation from an epinephrine test in rats. Methods: Male Wistar rats were treated with a continuous ethanol liquid diet for 7 weeks, and then subjected to 1-day withdrawal or 21-day abstinence. Ventricular ectopy was evaluated by 24-hour electrocardiographic telemetry recording; whole-body sympathetic activation, cardiac sympathovagal balance, and susceptibility to ventricular arrhythmia induced by sympathetic stimulation were evaluated based on blood noradrenalin metabolite concentrations, heart rate variability, and a 3-step epinephrine test. Results: Ventricular arrhythmia and related death were observed only in rats at 1 day of withdrawal, but not in nonalcoholic, continuous ethanol intake or 21-day abstinence rats. One-day withdrawal after a 7-week continuous ethanol regimen elevated circulating noradrenalin metabolite levels and induced cardiac sympathovagal imbalance. Deaths related to the epinephrine test and ventricular arrhythmia induced by low doses of epinephrine were observed only in 1-day withdrawal rats. However, all anomalies were normalized by 21-day abstinence. Conclusions: Abrupt termination of a 7-week continuous ethanol regimen is sufficient to enhance the whole-body sympathetic activation and cardiac sympathovagal imbalance that contribute to ventricular arrhythmia and sudden death in alcoholic rats. Those providing medical care for alcoholics, including in cases of legal imprisonment, should be aware of the possibility of enhanced susceptibility to sudden arrhythmic death due to the abrupt termination of a chronic ethanol regimen. [ABSTRACT FROM AUTHOR]

1. The most usual form of chronic hypoxia in humans is the intermittent hypoxia resulting from obstructive sleep apnoea (OSA). The OSA syndrome is a highly prevalent sleep breathing disorder that is considered an independent risk factor for hypertension and cardiovascular diseases. Endothelial dysfunction, oxidative stress, inflammation and sympathetic activation have been proposed as potential mechanisms involved in the onset of the hypertension. However, evidence for a unique pathogenic mechanism has been difficult to establish in OSA patients because of concomitant comorbidities. Thus, animal models have been developed to study the pathological consequences of exposure to chronic intermittent hypoxia (CIH). 2. Because OSA patients and animals exposed to CIH show augmented ventilatory, sympathetic and cardiovascular responses to acute hypoxia, it has been proposed that enhanced carotid body responsiveness to hypoxia is involved in the autonomic changes induced by OSA and in the development of the hypertension. Recently, this proposal has received further support from recordings of carotid body chemosensory neural discharges in situ and in vitro showing that exposure of animals to CIH increases basal carotid body chemosensory discharges and enhances the chemosensory response to hypoxia. 3. In the present brief review, we discuss the evidence supporting an important role for the carotid body in the progression of cardiorespiratory changes induced by OSA and the contribution of oxidative stress, endothelin-1 and pro-inflammatory molecules in the potentiation of the carotid body chemosensory function induced by CIH. [ABSTRACT FROM AUTHOR]

Intermittent hypoxia (TM) commonly occurs in patients with obstructive sleep apnea and can cause a wide range of pathology, including reduced left ventricular (LV) ejection fraction in rats as determined by echocardiography, in rodent models. We utilized echocardiography and pressure-volume (PV) loop analyses to determine whether LV contractility was decreased in inbred C57BL/6J mice exposed to IH and whether blockade of β-adrenergic receptors modified the response to hypoxia. Adult male 9- to 10-wk-old mice were exposed to 4 wk of IH (nadir inspired O2 5-6% at 60 cycles/h for 12 h during the light period) or intermittent air (IA) as control. A second group of animals were exposed to the same regimen of IH or IA, but in the presence of nonspecific 13-blockade with propranolol. Cardiac function was assessed by echocardiography and PV loop analyses, and mRNA and protein expression in ventricular homogenates was determined. Contrary to our expectations, we found with PV loop analyses that LV ejection fraction (63.4 ± 3.5 vs. 50.5 ± 2.6%, P = 0.015) and other measures of LV contractility were increased in IH-exposed animals compared with IA controls. There were no changes in contractile proteins, atrial natriuretic peptide levels, LV posterior wall thickness, or heart weight with lH exposure. However, cAMP levels were elevated after IH, and propranolol administration attenuated the increase in LV contractility induced by IH exposure. We conclude that, contrary to our hypothesis, 4 wk of IH exposure in C57BL/6J mice causes an increase in LV contractility that occurs independent of ventricular hypertrophy and is, in part, mediated by activation of cardiac 13-adrenergic pathways. [ABSTRACT FROM AUTHOR]

Introduction. In the present study, we introduce clitoral photoplethysmography as an instrument to assess clitoral blood volume (CBV). In research on female sexual functioning, vaginal pulse amplitude (VPA), as measured using vaginal photoplethysmography, has been used extensively as a measure of vaginal vasocongestion. Measurement of clitoral blood flow has thus far been problematic, mainly because of methodological constraints. Aim. To demonstrate that CBV is a valuable, easy to use complementary measure for the female sexual response, offering additional information to the VPA. Methods. Thirty women with and without female sexual dysfunction (FSD) watched neutral and erotic film clips. At the end of the erotic clip, the session was interrupted to induce inhibition of the sexual response. Another neutral clip followed the interruption. VPA and CBV were measured simultaneously, as well as skin conductance levels (SCLs), to assess the amount of sympathetic activity. Main Outcome Measures. VPA, CBV, SCL. Results. For both FSD and non-FSD women, VPA and CBV increased when sexually explicit material was presented. Changes in skin conductance significantly predicted changes in CBV ( b = −0.61, t[27] = −3.88, P < 0.001), but not in VPA. A large increase in sympathetic activity was accompanied by a large decrease in CBV. Furthermore, a large increase in CBV at the end of the erotic film clip presentation, as compared with the neutral clip, was accompanied by a relatively small increase in VPA ( b = −0.39, t[29] = −2.25, P < 0.033). Conclusion. CBV is a valid and sensitive tool to measure the female genital response. In the present study, it was particularly useful in investigating sexual inhibition, when used in combination with SCL. Furthermore, high CBV appeared to inhibit VPA, suggesting that VPA reflects an automatic preparatory response rather than genital arousal per se. Gerritsen J, van der Made F, Bloemers J, van Ham D, Kleiverda G, Everaerd W, Olivier B, Levin R, and Tuiten A. The clitoral photoplethysmograph: A new way of assessing genital arousal in women. J Sex Med 2009;6:1678–1687. [ABSTRACT FROM AUTHOR]

Three studies tested the hypothesis that negative metacognitive interpretations of anxious arousal under stereotype threat create cognitive deficits in intellectually threatening environments. Study 1 showed that among minority and White undergraduates, anxiety about an intelligence test predicted lower working memory when participants were primed with doubt as compared to confidence. Study 2 replicated this pattern with women and showed it to be unique to intellectually threatening environments. Study 3 used emotional reappraisal as an individual difference measure of the tendency to metacognitively reinterpret negative emotions and found that when sympathetic activation was high (indexed by salivary alpha-amylase), women who tended to reappraise negative feelings performed better in math and felt less self-doubt than those low in reappraisal. Overall, findings highlight how metacognitive interpretations of affect can undermine cognitive efficiency under stereotype threat and offer implications for the situational and individual difference variables that buffer people from these effects. [ABSTRACT FROM AUTHOR]

Abstract: Syringin is an active principle purified from the rhizome and root parts of Eleutherococcus senticosus (Araliaceae). The present study is designed to clarify the role of sympathetic activation in the insulinotropic effect of syringin. Plasma glucose lowering effect accompanying with the increase of plasma insulin and C-peptide were obtained in pentobarbital anesthetized Wistar rats 60min after an intravenous (i.v.) injection of syringin (100μg/kg). However, neither the plasma glucose lowering action, nor the raised plasma levels of insulin and C-peptide can be obtained in conscious rats received same syringin treatment. Otherwise, the insulin-releasing and plasma glucose lowering actions of syringin (100μg/kg, i.v.) were appeared in conscious rats under chemical sympathectomy using an intraperitoneal injection of guanethidine. In addition, plasma glucose lowering action of syringin (100μg/kg, i.v.) was observed in conscious rats with α1-adrenoceptor blockade by prazosin. The stimulatory actions of syringin on the secretion of plasma insulin and C-peptide were also obtained in prazosin-treated conscious rats. The obtained results suggest that insulinotropic effect of syringin on the plasma glucose regulation is impaired in conscious rats with a regular sympathetic tone; decrease of sympathetic tone as observed in anesthetized animal might be helpful in the therapeutic benefit of syringin. [Copyright &y& Elsevier]

Abstract: Human females are more sensitive than males to brief nociceptive stimuli such as heat and cold. However, a more pronounced peripheral vasoconstriction by females than by males during prolonged nociceptive stimulation predicts that females would be more sensitive to prolonged cold but not heat stimulation. We tested this possibility with reflex (lick/guard) and operant escape and preference tests of sensitivity to prolonged stimulation of Long-Evans and Sprague-Dawley rats. Escape responses to cold stimulation revealed a greater sensitivity of females. In contrast, males were more sensitive to nociceptive heat stimulation. An operant preference test of relative sensitivity to cold or heat stimulation confirmed these results. Cold was more aversive than heat for females, but heat was more aversive than cold for males. Recordings of skin temperature during nociceptive heat stimulation were consistent with the results of operant testing. A reduction in skin temperature (peripheral vasoconstriction) during nociceptive stimulation should increase cold sensitivity as observed for females relative to males. Lick/guard testing did not confirm the results of operant testing. Lick/guard (L/G) responding to nociceptive heat stimulation was greater for females than for males. Female escape responses to heat were more variable than males, but L/G responding of males to the same stimulus was more variable than for females. Perspective: A variety of chronic pain conditions are more prevalent for females, and psychological stress (with attendant sympathetic activation) is implicated in development and maintenance of these conditions. Therefore, understanding relationships between gender differences in pain sensitivity and sympathetic activation could shed light on mechanisms for some varieties of chronic pain. [Copyright &y& Elsevier]

Abstract: Objective: Sympathetic baroreflex sensitivity (symBRS) can be defined as the maximum sensitivity of muscle sympathetic nerve activity (MSNA) to changes in arterial blood pressure. This sensitivity is the slope of the linear middle part of the sigmoid curve that relates blood pressure to MSNA. SymBRS is known to vary with conditions, for instance during cold pressor testing. We investigated whether symBRS is affected by infusions of phenylephrine and nitroprusside. Methods: In 10 healthy subjects, vasoactive infusions were varied in slow steps, as customary in protocols to determine ‘graded infusion symBRS’ (symBRSinf). During each step, symBRS was estimated from spontaneous beat-to-beat fluctuations (symBRSsp). As a secondary goal, symBRSinf was compared to the symBRSsp without infusions. Results: The symBRSsp for MSNA burst area varied with infusions, augmenting with decreasing blood pressure, however the symBRSsp for burst occurrence was not affected. There were large differences between symBRSinf and symBRSsp at rest. Conclusions: symBRSsp varies systematically with infusions during a symBRSinf protocol. This denotes a fundamental difference between these methods. Significance: The relationship between ‘slow’ infusion effects (symBRSinf) and changes in symBRSsp is elucidated. The mathematical model that describes this relationship can also explain the increase of symBRS found with other sympathoexcitatory stimuli. [Copyright &y& Elsevier]

Abstract: The definition of generalized anxiety disorder (GAD) has been narrowed in successive editions of DSM by emphasizing intrusive worry and deemphasizing somatic symptoms of hyperarousal. We tried to determine the clinical characteristics of more broadly defined chronically anxious patients, and whether they would show physiological signs of sympathetic activation. A group whose chief complaint was frequent, unpleasant tension over at least the last six weeks for which they desired treatment, was compared with a group who described themselves as calm. Participants were assessed with structured interviews and questionnaires. Finger skin conductance, motor activity, and ambient temperature were measured for 24h. Results show that during waking and in bed at night, runs of continuous minute-by-minute skin conductance level (SCL) declines were skewed towards being shorter in the tense group than in the calm group. In addition, during waking, distributions of minute SCLs were skewed towards higher levels in the tense group, although overall mean SCL did not differ. Thus, the tense group showed a failure to periodically reduce sympathetic tone, presumably a corollary of failure to relax. We conclude that broader GAD criteria include a substantial number of chronically anxious and hyperaroused patients who do not fall within standard criteria. Such patients deserve attention by clinicians and researchers. [Copyright &y& Elsevier]

It is still unclear whether the low-frequency oscillation in heart rate is generated by an endogenous neural oscillator or by a baroreflex resonance. Our aim was to investigate this issue by analyzing blood pressure and heart rate variability and the baroreflex function in paraplegic subjects with spinal cord injury below the fourth thoracic vertebra. These subjects were selected because they represent a model of intact central neural drive to the heart, with a partially impaired autonomic control of the vessels. In our study, arterial blood pressure and ECG were recorded in 33 able-bodied controls and in 33 subjects with spinal cord lesions between the fifth thoracic and the fourth lumbar vertebra 1) during supine rest (lowest sympathetic activation), 2) sitting on a wheelchair (light sympathetic activation), and 3) during exercise (moderate sympathetic activation). Blood pressure and heart rate spectra, coherence, and baroreflex function (sequence technique) were estimated in each condition. Compared with controls, paraplegic subjects showed a reduction of the low-frequency power of blood pressure and heart rate, and, unlike controls, a 0.1-Hz peak did not appear in their spectra. Sympathetic activation increased the 0.1-Hz peak of blood pressure and heart rate and the coherence at 0.1 Hz in controls only. Paraplegic subjects also had significantly lower baroreflex effectiveness and greater blood pressure variability. In conclusion, the disappearance of the 10-s oscillation of heart rate and blood pressure in subjects with spinal cord lesion supports the hypothesis of the baroreflex nature of this phenomenon. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

• 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]

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]

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]

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]

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]

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]

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.)

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.