Sympathetic Nervous System Activity Research Articles

The Effects of Slow Breathing during Inter-Set Recovery on Power Performance in the Barbell Back Squat

Slow breathing (SB) reduces sympathetic nervous system activity, the heart rate (HR), and blood pressure (BP) and increases parasympathetic nervous system activity, HR variability, and oxygen saturation which may lead to quicker recovery between bouts of exercise. Therefore, the purpose of this study was to examine whether a SB technique using the 4-7-8 method between sets of barbell back squats (SQs) would attenuate drops in power and bar velocity. In a randomized, crossover design, 18 healthy resistance-trained college-aged males (age: 20.7 ± 1.4 years, body height: 178.6 ± 6.4 cm, body mass: 82.2 ± 15.0 kg, 4.5 ± 2.4 years of experience) performed 5 sets of 3 repetitions of SQs with normal breathing (CON) or SB during the 3-min recovery between sets. Peak and average power and bar velocity were assessed using a linear positioning transducer. HR recovery (RHR), systolic BP recovery (RBP), the rating of perceived exertion (RPE) and the rating of perceived recovery score (RS) were assessed after each set. There were no significant differences between conditions for peak and average power and bar velocity, RBP, RPE, and RS (p > 0.211). SB led to a greater RHR after set 2 (SB: 51.0 ± 14.9 bpm vs. CON: 44.5 ± 11.5 bpm, p = 0.025) and 3 (SB: 48.3 ± 13.5 bpm vs. CON: 37.7 ± 11.7 bpm, p = 0.006) compared to the CON condition. SB was well tolerated, did not hinder nor improve training performance and improved RHR after the middle sets of SQs. Further investigations are warranted to examine the effects of other SB techniques and to determine SB’s effects on different training stimuli as well as its effects over an entire workout and post-workout recovery metrics.

Natriuretic peptide pathways in heart failure in the context of the analysis of the mechanism of action and potential usages of sacubitril/valsartan

Natriuretic peptide pathways in heart failure in the context of the analysis of the mechanism of action and potential usages of sacubitril/valsartan

Does dysautonomia contribute to inappropriate sinus tachycardia in patients with post-COVID-19 syndrome?

Abstract Funding Acknowledgements None. Introduction Post-COVID-19 syndrome (PCS) refers to a wide spectrum of health issues experienced by individuals who have previously had COVID-19, starting three months after acute COVID-19 and enduring for a minimum of two months. Approximately 20% of PCS patients encounter inappropriate sinus tachycardia (IST), defined as the mean 24-hour heart rate greater than 90 bpm. IST is often accompanied by symptoms including palpitations and breathlessness that hinder patients in their daily tasks. Previous research has suggested that dysautonomia, a dysfunction in the autonomic nervous system, might underlie most PCS symptoms. Yet, its role in the development of IST within the context of PCS has not been fully investigated. Purpose This retrospective study examines IST prevalence and cardiovascular symptoms in PCS patients. It also assesses cardiac autonomic function through analysing the time and frequency fluctuations between successive heart rates, termed heart rate variability, to investigate the role of dysautonomia in the development of IST in PCS. Methods Patients who continued to experience PCS symptoms 12 weeks after their initial SARS-CoV-2 infection were referred to a multidisciplinary PCS unit at our hospital. Using our electronic patient record system, we identified 685 eligible patients who underwent 24-hour Holter monitoring between March 2020 and February 2023. After excluding patients with various conditions that could affect heart rate, we performed a comparative sub-analysis on 524 patients, dividing them into two age- and gender-matched groups of IST (n=100) and non-IST (n=424). The ECG data extracted from the 24-hour Holter records of these patients were entered into the KUBIOS software for HRV analysis and assessment of sympathetic and parasympathetic activity which could indicate cardiac dysautonomia. Demographic data was analysed using basic descriptive statistics and a chi-square test between the two groups. The normality of each parameter was tested using the Shapiro-Wilk test. Using Mann-Whitney and unpaired t-tests, we statistically analysed the differences between the IST and non-IST groups on the GraphPad Prism software. Results The LF/HF ratio was significantly higher in the IST group (2.78 ± 1.89) compared to the non-IST group (2.15 ± 1.93, p<0.001). The sympathetic nervous system (SNS) index was significantly higher in the IST group (1.50 ± 0.77 versus -0.13 ±0.70, p<0.001), whilst the parasympathetic nervous system (PNS) index was significantly lower in the IST group (-1.75 ± 0.65 versus -0.16 ± 1.61, p<0.001). Conclusions In PCS patients with IST, cardiac dysautonomia leads to a shift in the cardiac sympathovagal balance towards PNS and subsequently increased SNS activity, with a more pronounced effect on the parasympathetic side. Addressing dysautonomia and promoting parasympathetic activity could thereby improve PCS diagnostic and treatment strategies to restore a balanced autonomic regulation of the heart.

From Social Stress and Isolation to Autonomic Nervous System Dysregulation in Suicidal Behavior.

In this narrative review we wanted to describe the relationship of autonomic nervous system activity with social environment and suicidal spectrum behaviors. Patients with suicidal ideation/suicide attempt have higher sympathetic nervous system (SNS) and lower parasympathetic nervous system (PNS) activity in resting conditions and during acute stress tasks compared with patients without suicidal ideation/suicide attempt. Death by suicide and violent suicide attempt also are related to SNS hyperactivation. Similarly, a SNS/PNS imbalance has been observed in people with childhood trauma, stressful life events or feelings of loneliness and isolation. Social support seems to increase PNS control and resilience. Due to the importance of the social context and stressful life events in suicidal behavior, SNS/PNS imbalance could act as a mediator in this relationship and be a source of relevant biomarkers. Childhood trauma and stressful life events may impair the autonomic nervous system response in suicidal patients. Loneliness, isolation and social support may act as moderators in acute stress situations.

Oxytocin and corticotropin-releasing hormone exaggerate nucleus tractus solitarii neuronal and synaptic activity following chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) in rodents mimics the hypoxia-induced elevation of blood pressure seen in individuals experiencing episodic breathing. The brainstem nucleus tractus solitarii (nTS) is the first site of visceral sensory afferent integration, and thus is critical for cardiorespiratory homeostasis and its adaptation during a variety of stressors. In addition, the paraventricular nucleus of the hypothalamus (PVN), in part through its nTS projections that contain oxytocin (OT) and/or corticotropin-releasing hormone (CRH), contributes to cardiorespiratory regulation. Within the nTS, these PVN-derived neuropeptides alter nTS activity and the cardiorespiratory response to hypoxia. Nevertheless, their contribution to nTS activity after CIH is not fully understood. We hypothesized that OT and CRH would increase nTS activity to a greater extent following CIH, and co-activation of OT+CRH receptors would further magnify nTS activity. Our data show that compared to their normoxic controls, 10days' CIH exaggerated nTS discharge, excitatory synaptic currents and Ca2+ influx in response to CRH, which were further enhanced by the addition of OT. CIH increased the tonic functional contribution of CRH receptors, which occurred with elevation of mRNA and protein. Together, our data demonstrate that intermittent hypoxia exaggerates the expression and function of neuropeptides on nTS activity. KEY POINTS: Episodic breathing and chronic intermittent hypoxia (CIH) are associated with autonomic dysregulation, including elevated sympathetic nervous system activity. Altered nucleus tractus solitarii (nTS) activity contributes to this response. Neurons originating in the paraventricular nucleus (PVN), including those containing oxytocin (OT) and corticotropin-releasing hormone (CRH), project to the nTS, and modulate the cardiorespiratory system. Their role in CIH is unknown. In this study, we focused on OT and CRH individually and together on nTS activity from rats exposed to either CIH or normoxia control. We show that after CIH, CRH alone and with OT increased to a greater extent overall nTS discharge, neuronal calcium influx, synaptic transmission to second-order nTS neurons, and OT and CRH receptor expression. These results provide insights into the underlying circuits and mechanisms contributing to autonomic dysfunction during periods of episodic breathing.

Effects of hearing acuity on psychophysiological responses to effortful speech perception

In recent studies, psychophysiological measures have been used as markers of listening effort, but there is limited research on the effect of hearing loss on such measures. The aim of the current study was to investigate the effect of hearing acuity on physiological responses and subjective measures acquired during different levels of listening demand, and to investigate the relationship between these measures. A total of 125 participants (37 males and 88 females, age range 37-72 years, pure-tone average hearing thresholds at the best ear between -5.0 to 68.8 dB HL and asymmetry between ears between 0.0 and 87.5 dB) completed a listening task. A speech reception threshold (SRT) test was used with target sentences spoken by a female voice masked by male speech. Listening demand was manipulated using three levels of intelligibility: 20% correct speech recognition, 50%, and 80% (IL20%, IL50%, IL80%, respectively). During the task, peak pupil dilation (PPD), heart rate (HR), pre-ejection period (PEP), respiratory sinus arrhythmia (RSA), and skin conductance level (SCL) were measured. For each condition, subjective ratings of effort, performance, difficulty, and tendency to give up were also collected. Linear mixed effects models tested the effect of intelligibility level, hearing acuity, hearing asymmetry, and tinnitus complaints on the physiological reactivity (compared to baseline) and subjective measures. PPD and PEP reactivity showed a non-monotonic relationship with intelligibility level, but no such effects were found for HR, RSA, or SCL reactivity. Participants with worse hearing acuity had lower PPD at all intelligibility levels and showed lower PEP baseline levels. Additionally, PPD and SCL reactivity were lower for participants who reported suffering from tinnitus complaints. For IL80%, but not IL50% or IL20%, participants with worse hearing acuity rated their listening effort to be relatively high compared to participants with better hearing. The reactivity of the different physiological measures were not or only weakly correlated with each other. Together, the results suggest that hearing acuity may be associated with altered sympathetic nervous system (re)activity. Research using psychophysiological measures as markers of listening effort to study the effect of hearing acuity on such measures are best served by the use of the PPD and PEP.

Increase in blood pressure precedes distress behavior in nursing home residents with dementia.

Distress behaviors in dementia (DBD) likely increase sympathetic nervous system activity. The aim of this study was to examine the associations among DBD, blood pressure (BP), and intensity of antihypertensive treatment, in nursing home (NH) residents with dementia. We identified long-stay Veterans Affairs NH residents with dementia in 2019-20 electronic health data. Each individual with a BP reading and a DBD incident according to a structured behavior note on a calendar day (DBD group) was compared with an individual with a BP reading but without a DBD incident on that same day (comparison group). In each group we calculated daily mean BP from 14 days before to 7 days after the DBD incident day. We then calculated the change in BP between the DBD incident day and, as baseline, the 7-day average of BP 1 week prior, and tested for differences between DBD and comparison groups in a generalized estimating equations multivariate model. The DBD and comparison groups consisted of 707 and 2328 individuals, respectively. The DBD group was older (74 vs. 72 y), was more likely to have severe cognitive impairment (13% vs. 8%), and had worse physical function scores (15 vs. 13 on 28-point scale). In the DBD group, mean systolic BP on the DBD incident day was 1.6 mmHg higher than baseline (p < .001), a change that was not observed in the comparison group. After adjusting for covariates, residents in the DBD group, but not the comparison group, had increased likelihood of having systolic BP > = 160 mmHg on DBD incident days (OR 1.02; 95%CI 1.00-1.03). Systolic BP in the DBD group began to rise 7 days before the DBD incident day and this rise persisted 1 week after. There were no significant changes in mean number of antihypertensive medications over this time period in either group. NH residents with dementia have higher BP when they experience DBD, and BP rises 7 days before the DBD incident. Clinicians should be aware of these findings when deciding intensity of BP treatment.

Research progress on the improvement of cardiovascular diseases through the autonomic nervous system regulation of the NLRP3 inflammasome pathway.

Cardiovascular disease stands as a leading global cause of mortality. Nucleotide-binding Oligomerization Domain-like Receptor Protein 3 (NLRP3) inflammasome is widely acknowledged as pivotal factor in specific cardiovascular disease progression, such as myocardial infarction, heart failure. Recent investigations underscore a close interconnection between autonomic nervous system (ANS) dysfunction and cardiac inflammation. It has been substantiated that sympathetic nervous system activation and vagus nerve stimulation (VNS) assumes critical roles withinNLRP3 inflammasome pathway regulation, thereby contributing to the amelioration of cardiac injury and enhancement of prognosis in heart diseases. This article reviews the nexus between NLRP3 inflammasome and cardiovascular disorders, elucidating the modulatory functions of the sympathetic and vagus nerves within the ANS with regard to NLRP3 inflammasome. Furthermore, it delves into the potential therapeutic utility of NLRP3 inflammasome to be targeted by VNS. This review serves as a valuable reference for further exploration into the potential mechanisms underlying VNS in the modulation of NLRP3 inflammasome.

Unearthing Subtle Cognitive Variations: A Digital Screening Tool for Detecting and Monitoring Mild Cognitive Impairment

Early diagnosis of mild cognitive impairment (MCI) is pivotal in mitigating the risk of cognitive impairment and the onset of dementia. However, prevailing clinical cognitive screening tests and biomarker assessment approaches often suffer from drawbacks such as high cost, invasiveness, time consumption, or subjectivity. In China, existing digital cognitive assessment tools face multiple challenges due to their distinctive cultural, language, and healthcare landscape. Therefore, we embarked on a study to develop a digital cognitive assessment tool, evaluate its efficacy in distinguishing between healthy individuals and MCI patients, and examine its acceptability among Chinese older adults. Through a series of symposiums, programming, and interviews with stakeholders, we iteratively designed the "BrainNursing" mobile application. The system consists of eleven single tasks and three dual tasks, each taking only 1–3 minutes. Subsequently, we conducted statistical comparisons of movement kinetics and physiological signals recorded during cognitive testing in 181 older adults to investigate which parameters could serve as effective digital biomarkers for MCI screening. Leveraging machine learning classifiers and a majority voting principle, we evaluated the classification performance of the BrainNursing system in detecting MCI, yielding an accuracy rate of 90.3%. Furthermore, our analysis of movement kinetics revealed that time, score, and sequence features are crucial in cognitive assessment. Contrasting with their healthy counterparts, MCI patients exhibited decreased heart rate variability, increased sympathetic nervous system activity, and weakened autonomic nervous system regulation in response to stimuli during cognitive testing. Finally, user experience feedback indicated that participants universally perceived BrainNursing as a convenient and user-friendly cognitive screening tool and provided valuable insights for further improvement.

Relation to Social Determinants in Cardiovascular Disease Risk Profile: An Alarming View

Globally, Cardiovascular disease (CVD) is one of the major reasons for mortality. Cardiovascular health in children and adults is profoundly affected by the milieu of early life. Currently, CVD is taking a different turn based on social antecedents like poverty, the difference in socio-economic status, gender inequality, being a fluid person, and work life in harmony increases the risk of getting into CVD, that too in vulnerable populations like racial and ethnic minorities, women, the elderly, the chronically ill individual with disabilities, lesbian, gay, bisexual, transgender, queer and racism play a significant role in conditioning disease burden and modulating outcomes of CVD. People with low socioeconomic status increase the hypothalamic pituitary adrenal axis (HPA axis) in the body, due to stress response, and at the end, increased cortisol and sympathetic nervous system activity lead to decreased angiogenic activity. People from low socioeconomic backgrounds, loneliness, and social isolation in many cases like racism, ethnic minorities, children, women, elderly, and chronically ill individuals with disabilities, are exposed to constant stress because of a lack of their fundamental needs. The wider introduction of universal screening for social factors that impact cardiac health will help to identify children and families at risk. Hence,aggressive screening tests beginning at an early age will be beneficial for early detection and treatment. Healthcare professionals need to pay attention to promotinghealth education and awareness aids to decrease CVD-associated mortality.

ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer (BCa) tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. ND is associated with shorter BCa recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity (NF-kB, AP-1), sympathetic nervous system (SNS) activity (CREB), and protective cellular responses (IRF, STAT). To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB, AP-1, down-regulated IRF, STAT) and SNS activation (up-regulated CREB). Increasing subjective ND (e.g., threat to safety), was associated with up-regulated NF-kB and CREB and down-regulated IRF. These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

The Relationship Between Sleep Quality and Blood Pressure in Students

Introduction: Sleep is one of the physiological needs that has an impact on the quality and balance of life. The habit of poor sleep quality or a short amount of sleep is also associated with an increase in an individual's blood pressure. If someone's sleep duration is short, the sympathetic nervous system activity will increase, making the person vulnerable to stress, ultimately leading to an increase in blood pressure. Poor sleep quality and quantity not only causes physical discomfort, but also impairs individual memory and cognitive abilities. If this poor quality and quantity of sleep is left unattended for several years, more dangerous complications are likely to occur, such as heart attacks, strokes and psychological problems (such as depression or other mood disorders). The purpose of the study was to determine the relationship between sleep quality and blood pressure in final semester students of the Faculty of Health Sciences, Universitas Sulawesi Barat.&#x0D; Methods: The study used a cross-sectional approach. The number of samples of 45 respondents was selected by simple random sampling technique&#x0D; Results: The results of the chi-square test showed that there was no relationship between sleep quality and blood pressure (p&gt;0.1).&#x0D; Conclusion: there is no significant relationship between sleep quality and blood pressure in students of the Faculty of Health Sciences in the Final Semester of the Universitas Sulawesi Barat.

Genetic ablation of Lmp2 increases the susceptibility for impaired cardiac function.

Proteasome degradation is an integral part of cellular growth and function. Proteasomal intervention may mitigate adverse myocardial remodeling, but is associated with the onset of heart failure. Previously, we have demonstrated that increasing abundance of cardiac Lmp2 and its incorporation into proteasome complexes is an endogenous mechanism for proteasome regulation during hypertrophic remodeling of the heart induced by chronic ß-adrenoreceptor stimulation. Here, we investigated whether Lmp2 is required for myocardial remodeling not driven by inflammation and show that Lmp2 is a tipping element for growth and function in the heart but not for proteasome insufficiency. While it has no apparent impact under unchallenged conditions, myocardial remodeling without Lmp2 exacerbates hypertrophy and restricts cardiac function. Under chronic ß-adrenoreceptor stimulation, as seen in the development of cardiovascular disease and the manifestation of heart failure, genetic ablation of Lmp2 in mice caused augmented concentric hypertrophy of the left ventricle. While the heart rate was similarly elevated as in wildtype, myocardial contractility was not maintained without Lmp2, and apparently uncoupled of the ß-adrenergic response. Normalized to the exacerbated myocardial mass, contractility was reduced by 41% of the pretreatment level, but would appear preserved at absolute level. The lack of Lmp2 interfered with elevated 26S proteasome activities during early cardiac remodeling reported previously, but did not cause bulk proteasome insufficiency, suggesting the Lmp2 containing proteasome subpopulation is required for a selected group of proteins to be degraded. In the myocardial interstitium, augmented collagen deposition suggested matrix stiffening in the absence of Lmp2. Indeed, echocardiography of left ventricular peak relaxation velocity (circumferential strain rate) was reduced in this treatment group. Overall, targeting Lmp2 in a condition mimicking chronic ß-adrenoreceptor stimulation exhibited the onset of heart failure. Anticancer therapy inhibiting proteasome activity, including Lmp2, is associated with adverse cardiac events, in particular heart failure. Sparing Lmp2 may be an avenue to reduce adverse cardiac events when chronic sympathetic nervous system activation cannot be excluded.

Electroacupuncture pretreatment mediates sympathetic nerves to alleviate myocardial ischemia–reperfusion injury via CRH neurons in the paraventricular nucleus of the hypothalamus

BackgroundMyocardial ischemia–reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia–reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons.MethodsIntegrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot.ResultsOur data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect.ConclusionEA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

Prospective measurement of skin conductance response during trauma interview predicts future PTSD severity in trauma exposed children

Previous cross-sectional studies have shown that sympathetic nervous system (SNS) arousal is positively associated with posttraumatic stress disorder (PTSD) symptoms in children with trauma exposure. One of the ways that SNS activity is measured is through skin conductance response (SCR), which has been shown to predict future PTSD severity in adults. In this study, we explored the utility of a novel, low-cost mobile SCR device, eSense, to predict future PTSD symptom severity in trauma exposed children. We recruited children (N = 43, age 9 years at initial visit) for a longitudinal study in which SCR was recorded at baseline visit, and PTSD symptoms were assessed two years later. Results indicated an interaction between SCR and trauma exposure, such that children with lower trauma exposure who demonstrated greater SCR reported higher PTSD severity two years later. This association remained significant even after controlling for baseline PTSD symptoms. Children with higher levels of trauma exposure did not show this association, potentially due to ceiling effects of PTSD symptoms. Together these findings suggest the utility of SCR as a biomarker for predicting trauma related disorders in children, and that it may be a valuable tool in clinical interventions targeting sympathetic arousal.

Influence of Brainstem's Area A5 on Sympathetic Outflow and Cardiorespiratory Dynamics.

Area A5 is a noradrenergic cell group in the brain stem characterised by its important role in triggering sympathetic activity, exerting a profound influence on the sympathetic outflow, which is instrumental in the modulation of cardiovascular functions, stress responses and various other physiological processes that are crucial for adaptation and survival mechanisms. Understanding the role of area A5, therefore, not only provides insights into the basic functioning of the sympathetic nervous system but also sheds light on the neuronal basis of a number of autonomic responses. In this review, we look deeper into the specifics of area A5, exploring its anatomical connections, its neurochemical properties and the mechanisms by which it influences sympathetic nervous system activity and cardiorespiratory regulation and, thus, contributes to the overall dynamics of the autonomic function in regulating body homeostasis.

Pharmacological Triggers of Takotsubo Cardiomyopathy: An Updated Review of Evidence and Recommendations.

Previous publications in 2011, 2016, and 2022 have presented lists of drugs associated with takotsubo cardiomyopathy (TCM). This review aims to provide updated drug lists that have been reported as potential causes of TCM. Following the same methodology employed in previous reviews, a detailed investigation was carried out in the PubMed/Medline database from June 2022 to July 2023 to identify drug-induced TCM (DITC) case reports. Various search terms related to the drug-induced transient left ventricular ballooning syndrome, ampulla cardiomyopathy, apical ballooning syndrome, drug-induced broken heart syndrome, drug triggered takotsubo cardiomyopathy, takotsubo cardiomyopathy, and iatrogenic takotsubo cardiomyopathy were utilized. Filters for fulltext availability, case reports, human studies, and English language were applied. Articles reporting drugs associated with TCM development were included in the analysis. Foremost 192 case reports were initially identified, with 75 drugs meeting the inclusion criteria after a thorough review. The latest revision identified seven drugs that might lead to TCM, with four drugs (57.14%) already reported in previous reviews and three drugs (42.86%) newly identified. Consequently, the updated drug list potentially triggering TCM in 2023 comprises a sum of 75 drugs. The recent 75 drugs provided additional evidence linking to TCM development. The updated list predominantly includes drugs that induce sympathetic overstimulation, although some drugs on the list have unclear associations with sympathetic nervous system activation.

Effectiveness of osteopathic manipulative applications on hypothalamic-pituitary-adrenal (HPA) axis in youth with major depressive disorder: a randomized double-blind, placebo-controlled trial.

Osteopathic treatments regulate the neurovegetative system through joint mobilizations and manipulations, and myofascial and craniosacral techniques. Despite the growing body of research, the precise impact of osteopathic medicine on the autonomic nervous system (ANS) is not yet fully elucidated. As to Kuchera's techniques, the stimulation of the sympathetic trunk and prevertebral ganglia contributed to harmonization of the sympathetic activity. However, potential relationships between the harmonization of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis largely remain uncertain and warrant further exploration. This study was designed to evaluate the effectiveness of the osteopathic sympathetic harmonization (OSH) on the SNS and the HPA axis in youth with major depressive disorder (MDD). The study included 39 youths aged 15-21 years and diagnosed with MDD. The participants were randomly assigned into either the OSH or the placebo group. Stimulation was performed on the sympathetic truncus and prevertebral ganglia in the OSH group. The stimulation of the placebo group was performed with a lighter touch and a shorter duration in similar areas. Each participant completed the Beck Depression Inventory (BDI) and the State and Trait Anxiety Inventory (SAI and TAI) before the application. Blood pressure (BP) and pulse measurements were made, and saliva samples were taken before, immediately after, and 20 min after application. The baseline BDI (p=0.617) and TAI (p=0.322) scores were similar in both groups. Although the SAI scores decreased in both groups postintervention, no statistically significant difference was found between the two groups. Subjects who received OSH had a decrease in α-amylase level (p=0.028) and an increase in cortisol level (p=0.009) 20 min after the procedure. Following OSH application in depressed youth, SNS activity may decrease, whereas HPA axis activity may increase. Future studies may examine the therapeutic efficacy of repeated OSH applications in depressed individuals.

Heart rate dynamics and asymmetry during sympathetic activity stimulation and post-stimulation recovery in ski mountaineers-a pilot exploratory study.

There is a lack of studies on non-linear heart rate (HR) variability in athletes. We aimed to assess the usefulness of short-term HR dynamics and asymmetry parameters to evaluate the neural modulation of cardiac activity based on non-stationary RR interval series by studying their changes during sympathetic nervous system activity stimulation (isometric handgrip test) and post-stimulation recovery in professional ski mountaineers. The correlation between the changes in the parameters and the respiratory rate (RespRate) and also the duration of the career was analyzed. Short-term (5 min) and ultra-short-term (1 min) rates of patterns with no variations (0V), number of acceleration runs of length 1 (AR1), and short-term Porta's Index were greater, whereas Guzik's Index (GI) was smaller during sympathetic stimulation compared to rest. GI increased and the number of AR1 decreased during recovery. Greater increases in GI and RMSSD were associated with greater decreases in RespRate during recovery. Greater increases in RespRate from rest to short-term sympathetic stimulation were associated with greater increases in 0V (Max-min method) and AR1 but also with greater decreases in decelerations of short-term variance and accelerations and decelerations of long-term variance. Greater increases in 0V (Max-min method) and number of AR1 during sympathetic stimulation were associated with a shorter career duration. Greater decreases in these parameters during recovery were associated with a longer career duration. Changes in measures of HR dynamics and asymmetry, calculated based on short-term non-stationary RRi time series induced by sympathetic stimulation and post-stimulation recovery, reflected sympathovagal shift and were associated with condition-related alterations in RespRate and career duration in athletes who practice ski mountaineering.

POPDC1 Variants Cause Atrioventricular Node Dysfunction and Arrhythmogenic Changes in Cardiac Electrophysiology and Intracellular Calcium Handling in Zebrafish.

Popeye domain-containing (POPDC) proteins selectively bind cAMP and mediate cellular responses to sympathetic nervous system (SNS) stimulation. The first discovered human genetic variant (POPDC1S201F) is associated with atrioventricular (AV) block, which is exacerbated by increased SNS activity. Zebrafish carrying the homologous mutation (popdc1S191F) display a similar phenotype to humans. To investigate the impact of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling, homozygous popdc1S191F and popdc1 knock-out (popdc1KO) zebrafish larvae and adult isolated popdc1S191F hearts were studied by functional fluorescent analysis. It was found that in popdc1S191F and popdc1KO larvae, heart rate (HR), AV delay, action potential (AP) and calcium transient (CaT) upstroke speed, and AP duration were less than in wild-type larvae, whereas CaT duration was greater. SNS stress by β-adrenergic receptor stimulation with isoproterenol increased HR, lengthened AV delay, slowed AP and CaT upstroke speed, and shortened AP and CaT duration, yet did not result in arrhythmias. In adult popdc1S191F zebrafish hearts, there was a higher incidence of AV block, slower AP upstroke speed, and longer AP duration compared to wild-type hearts, with no differences in CaT. SNS stress increased AV delay and led to further AV block in popdc1S191F hearts while decreasing AP and CaT duration. Overall, we have revealed that arrhythmogenic effects of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling in zebrafish are varied, but already present in early development, and that AV node dysfunction may underlie SNS-induced arrhythmogenesis associated with popdc1 mutation in adults.