Cardiac Sympathetic Nerve Activity Research Articles

Remote ischemic peri-conditioning suppressed cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction

Abstract Background Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). However, it remains to be elucidated whether RIPC affects the cardiac sympathetic nerve activity in patients with AMI. Purpose The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion respectively in patients with AMI. Methods We randomly assigned 157 patients with suspected AMI undergoing emergent PCI to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80). After excluding inappropriate patients such as those with other diagnosis than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). CSNA was assessed in the culprit and non-culprit lesion respectively by the cardiac MIBG SPECT imaging. Results Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. Patients in RIPC group tended to show higher late uptake only in the non-culprit lesion at discharge. At 1 year after discharge, patients in RIPC group demonstrated significantly higher late uptake (p=0.021) and lower washout rate (p=0.013) than those in control group in the non-culprit lesion. Regarding the culprit lesion, only washout rate tended to be lower in RIPC group at 1 year after discharge. Conclusion(s): Remote ischemic peri-conditioning showed suppressive effect on cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction.SPECT parameters in RIPC and control

The activation of cardiac sympathetic nervous system in the non-culprit lesion is a strong prognostic predictor in patients with acute myocardial infarction

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). However, it remains to be determined whether regional assessment of cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion of the cardiac MIBG SPECT imaging could have prognostic value in patients with AMI. Purpose The purpose of this study is to investigate the prognostic impact of regional CSNA in patients with AMI. Methods We prospectively enrolled 122 patients with AMI who visited our emergency department and underwent primary percutaneous coronary intervention. The late heart-to-mediastinum ratio (HMR) and washout rate (WR) was calculated to assess CSNA in the whole heart from planar images of in the cardiac MIBG imaging. The MIBG SPECT image parameters were calculated for each coronary artery, and the average WR in the culprit and non-culprit lesion were evaluated to assess the regional status of CSNA in patients with AMI. Abnormal WR in planar image was defined as 34% or more, as previously reported. The cut-off value of late HMR in planar image, WR in the culprit and non-culprit lesions were determined by ROC analysis. The primary endpoint was major adverse cardiac event (MACE) including all cause death, myocardial infarction, hospitalization for heart failure and target lesion revascularization. Results During a mean follow-up period of 3.1±1.8 years, 25 of 122 patients underwent MACE. The late HMR (p=0.004), WR in planar image (p=0.002), WR in the culprit lesion (p=0.023), and WR in the non-culprit lesion (p<0.001) were significantly associated with MACE at univariate Cox proportional hazard analysis. The increased WR in the non-culprit lesion (defined as 28.3% or more: AUC 0.697 [0.576-0.817]) was significantly independently associated with MACE (hazard ratio: 4.36 [1.45-13.11], p=0.009) even adjusted by late HMR, WR in planar image or WR in the culprit lesion, while decreased HMR, abnormal WR in planar image and increased WR in the culprit lesion showed no significant association with MACE in the multivariate model with WR in the non-culprit lesion. Kaplan-Meier analysis revealed that patients with increased WR in the non-culprit lesion had significantly higher risk for MACE than those without increased WR (45% vs 11% p<0.001). Conclusion(s) The activation of cardiac sympathetic nervous system in the non-culprit lesion is particularly associated with poor prognosis in patients with acute myocardial infarction.MACE risk by WR in non-culprit lesion

The sympathetic nervous system in heart failure with preserved ejection fraction.

The sympathetic nervous system (SNS) is a major mediator of cardiovascular physiology during exercise in healthy people. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal symptom, has remained relatively unexplored. The present review summarizes and critically explores the currently limited data on SNS changes in HFpEF patients with a particular emphasis on caveats of the data and the implications for its subsequent interpretation. While direct measurements of SNS activity in HFpEF patients is scarce, modest increases in resting levels of muscle sympathetic nerve activity are apparent, although this may be due to the co-morbidities associated with the syndrome rather than HFpEF per se. In addition, despite some evidence for dysfunctional sympathetic signaling in the heart, there is no clear evidence for elevated cardiac sympathetic nerve activity. The lack of a compelling prognostic benefit with use of β-blockers in HFpEF patients also suggests a lack of sympathetic hyperactivity to the heart. Similarly, while renal and splanchnic denervation studies have been performed in HFpEF patients, there is no concrete evidence that the sympathetic nerves innervating these organs exhibit heightened activity. Taken together, the totality of data suggests limited evidence for elevated sympathetic nerve activity in HFpEF and that any SNS perturbations that do occur are not universal to all HFpEF patients. Finally, how the SNS responds during exertion in HFpEF patients remains unknown and requires urgent investigation.

Remote ischemic periconditioning suppresses cardiac sympathetic activation in acute myocardial infarction: a randomized controlled trial.

Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). However, whether RIPC affects the cardiac sympathetic nerve activity in patients with STEMI remains unclear. This study investigated the effects of RIPC on cardiac sympathetic nerve activity in patients with STEMI. We prospectively assigned patients with STEMI who underwent emergent PCI to receive RIPC or no procedure (control group) upon arrival at the cardiac catheterization laboratory. The primary endpoint was cardiac sympathetic nerve activity assessed through the washout rate (WR) in cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging. Patients in the RIPC (n = 62) and control (n = 60) groups had similar demographic and clinical characteristics at baseline. Multivariable linear regression models revealed that the culprit lesion of the left anterior descending artery and hemoglobin level were significantly and independently associated with WR at discharge. WRs of the groups differed insignificantly at discharge. However, the RIPC group (n = 49) showed significantly lower WR than the control group (n = 47) at 1year after discharge (p = 0.027). In the single-photon emission computed tomography analysis at 1year after discharge, the RIPC group demonstrated significantly higher late uptake (p = 0.021) and lower WR (p = 0.013) in the nonculprit lesion, with a non-significant decrease in WR for the culprit lesion. RIPC can suppress augmented cardiac sympathetic nerve activity in patients with STEMI, particularly in nonculprit lesions.

Alleviation of physiological stress response by apple aroma

ABSTRACT Objective The study evaluated the potential of apple aroma to alleviate physiological stress response induced by a short-term cognitive stressor. It investigated the effects of apple aroma on cardiac and peripheral autonomic nervous system activity under stressful conditions. Methods Within-subject experiments were conducted with 25 healthy male university students with a 30-minute calculation task under three conditions: Apple, Chamomile (CHA), and Di propylene glycol (DPG) (scentless air). The aroma administration was precisely controlled and counterbalanced. Cardiac activity on electrocardiograms and nose tip temperature were recorded throughout the experiment. A visual analog scale and a scent questionnaire were subjective measures. Results Apple aroma demonstrated a significantly smaller increase in heart rate (t [24] = 3.36, p = 0.008 vs. DPG, t [24] = 4.06, p = 0.001 vs. CHA), and a decrease in the high-frequency component of heart rate variability (t [24] = 2.81, p = 0.029 vs. DPG, t [24] = 3.48, p = 0.006 vs. CHA) compared to the other conditions, representing a smaller enhancement of cardiac sympathetic nervous system activity and smaller suppression of cardiac parasympathetic nervous system activity respectively. Conclusion Apple aroma showed efficacy in alleviating the physiological stress response in terms of cardiac activity. Apple was also considered significantly preferable and comfortable compared to the other conditions, which would be beneficial in the context of aromatherapy.

Cardiac sympathetic nerve activity and its implications for heart function and failure.

Cardiac sympathetic nerve activity and its implications for heart function and failure.

Abstract Mo073: Elucidating the Role of Cardiac Radiotherapy on the Sympathetic Nervous System as a Treatment for Ventricular Tachycardia

Ventricular tachycardia (VT) is a dangerous arrhythmia that occurs in structurally and electrically heterogenous regions of the diseased heart, leading to sudden cardiac arrest and death if left untreated. One of the main drivers underlying the arrhythmogenic substrate is abnormal remodeling of the autonomic nervous system after cardiac injury, resulting in a heterogenous distribution of sympathetic innervation and subsequent ventricular arrhythmia. In patients with VT refractory to conventional therapy, noninvasive cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising new treatment. Here, we investigated whether cardiac radiotherapy homogenizes the arrhythmogenic substrate through induction of cardiac sympathetic nerve innervation and activity in a closed-chest ischemia reperfusion murine model of ischemic heart failure. Using single nucleus-RNA sequencing, we identified global transcriptomic changes in the left ventricle 6 weeks after 25 Gray (Gy) cardiac X-ray radiation. Notably, these changes included increased expression of neurotrophins such as brain derived neurotrophic factor, a growth factor essential for neuronal survival and development, in irradiated hearts compared to sham controls. Consequently, Western blot and immunofluorescence showed increased expression of the sympathetic neuronal markers tyrosine hydroxylase and neuropeptide Y at the scar border zone of irradiated mice. Similar immunofluorescence results were observed at the irradiated border zone from the explanted heart of a patient previously targeted with 25 Gy compared to a nontargeted remote region within the same heart. These findings suggest a novel role for radiation-induced remodeling of the sympathetic nervous system in the anti-arrhythmic response to SBRT.

Sympathetic transduction of cardiac sympathetic nerve activity in healthy, conscious sheep.

Sympathetic transduction is the study of how impulses of sympathetic nerve activity (SNA) affect end-organ function. Recently, the transduction of resting bursts of muscle SNA (MSNA) has been investigated and shown to have a role in the maintenance of blood pressure through changes in vascular tone in humans. In the present study, we investigate whether directly recorded resting cardiac SNA (CSNA) regulates heart rate (HR), coronary blood flow (CoBF), coronary vascular conductance (CVC), cardiac output (CO) and mean arterial pressure. Instrumentation was undertaken to record CSNA and relevant vascular variables in conscious sheep. Recordings were performed at baseline, as well as after the infusion of a β-adrenoceptor blocker (propranolol) to determine the role of β-adrenergic signalling in sympathetic transduction in the heart. The results show that after every burst of CSNA, there was a significant effect of time on HR (n=10, ∆: +2.1±1.4 beatsmin-1 , P=0.002) and CO (n=8, ∆: +100±150mLmin-1 , P=0.002) was elevated, followed by an increase in CoBF (n=9, ∆: +0.76mLmin-1 , P=0.001) and CVC (n=8, ∆: +0.0038mLmin-1 mmHg-1 , P=0.0028). The changes in HR were graded depending on the size and pattern of CSNA bursts. The HR response was significantly attenuated after the infusion of propranolol. Our study is the first to explore resting sympathetic transduction in the heart, suggesting that CSNA can dynamically change HR mediated by an action on β-adrenoceptors. KEY POINTS: Sympathetic transduction is the study of how impulses of sympathetic nerve activity (SNA) affect end-organ function. Previous studies have examined sympathetic transduction primarily in the skeletal muscle and shown that bursts of muscle SNA alter blood flow to skeletal muscle and mean arterial pressure, although this has not been examined in the heart. We investigated sympathetic transduction in the heart and show that, in the conscious condition, the size of bursts of SNA to the heart can result in incremental increases in heart rate and coronary blood flow mediated by β-adrenoceptors. The pattern of bursts of SNA to the heart also resulted in incremental increases in heart rate mediated by β-adrenoceptors. This is the first study to explore the transduction of bursts of SNA to the heart.

Chronic Expression of Interleukin-10 Transgene Modulates Cardiac Sympathetic Ganglion Resulting in Reduced Ventricular Arrhythmia.

The cardiac autonomic nervous system (CANS) is intimately connected to the regulation of electrophysiology and arrhythmogenesis in cardiac systems. This work aimed at investigating whether interleukin-10 (IL-10) could effectively modulate CANS and suppress ischemia-induced ventricular arrhythmia (VA) through chronically acting on the cardiac sympathetic ganglion (CSG). Using an adeno-associated virus (AAV), we achieved local chronic overproduction of IL-10 in the CSG, left stellate ganglion (LSG). As a result, in the IL-10 group, we observed a decreased number of tyrosine hydroxylase-positive (TH+) cells in the LSG. IL-10 markedly downregulated the nerve growth factor, synaptophysin, as well as growth-associated protein 43 expression. In vivo, results from ambulatory electrocardiography showed that IL-10 overexpression significantly inhibited the cardiac sympathetic nervous system activity and improved heart rate variability. Meanwhile, we observed decreased LSG function as well as prolonged ventricular effective refractory period and suppressed VA after myocardial infarction (MI) in the IL-10 group. In addition, IL-10 overexpression attenuated inflammation and decreased norepinephrine levels in the myocardium after acute MI. In conclusion, our data suggest that chronic IL-10 overexpression modulates cardiac sympathetic nerve remodeling and suppresses VA induced by MI. Neuromodulation through AAV-mediated IL-10 overexpression may have the characteristics of and advantages as a potential neuroimmunotherapy for preventing MI-induced VAs.

Stellate ganglion, inflammation, and arrhythmias: a new perspective on neuroimmune regulation.

Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.

Cardiac Sympathetic Nerve Activity among Passive Smokers and Smokeless Tobacco Users: A Cross-sectional Study

Introduction: Tobacco use and exposure to Second-Hand Smoke (SHS) are major health hazards for growing children and adolescents. Smokeless Tobacco (SLT) product consumption is a serious health issue both abroad and in India. Children and young people are more likely to be exposed to Secondhand Smoke (SHS) in India due to high population density. Aim: To assess physical anthropometric parameters and cardiac autonomic function tests among passive smokers and SLT users. Materials and Methods: This cross-sectional study was conducted in the department of Physiology Nootan Medical College and Research Centre, Visnagar from August 2023 to February 2024. The study was comprised of 100 participants including 50 non-smokers who chew tobacco and who have never been a passive smoker in Group-A (SLT) and 50 agematched passive smokers who lived with at least one smoker or frequently interacted with smokers at work for at least three years before conducting this study was included in Group-B (Passive smoke or SHS). Anthropometric measurements were recorded. Cardiac autonomic function tests were done by using a Polyrite recording machine with mode “ECG” in Lead-II position among both groups. Results were expressed as mean±Standard Deviation (SD), and analysed by using unpaired student’s t-test. The p-value of <0.05 was considered as statistically significant. Results: Resting (Basal) heart rate was significantly increased in the SLT group (p-value≤0.001). Resting Systolic Blood Pressure (SBP) was significantly reduced in the passive smoker group when compared to SLT group (p-value≤0.001). It was noted that 30:15 ratio was statistically significant in the passive smokers as compared to that in the SLT group (p-value≤0.001). It was also noted that blood pressure response to immediate standing in passive smokers was highly significant (p-value≤0.001). Conclusion: The results of present study showed that sympathetic activity was increased and parasympathetic activity was decreased in tobacco users (SLT). The fall of SBP in response to immediate standing among passive smokers is suggestive of decreased central sympathetic activity and baroreceptor reflex sensitivity

The New Trends in Physiological and Pathological Actions of Ghrelin (Brain-Heart Axis) on the Heart and Cardiovascular System

Background: Ghrelin increased significantly the Left Ventriculus Eject Fraction and end-systolic volume after 30 minutes of intra-venous injection and without alterations heart rate and blood pressure. Ghrelin was discovered in 1999 as an only one 28 amino acid peptides (with octanoyl serine group) located on the short arm of chromosome 3 (position 3p25-26) having six exons, two are noncoding and four introns and encodes a 511 bp mRNA. Ghrelin is synthesized by the endocrine X/A-like cells located from the gastric fundus mucosa through the whole mucosa of the medium right vertical side of the stomach until to the 1 inch before anatomical pylorus. These cells are responsible to produced 80% of the whole ghrelin produced in the human body. Furthermore, other place of this production occurs at the hypothalamus, the pituitary, second portion of duodenum, pancreas, heart and other tissues. Bibliographic references also demonstrate the importance of ghrelin’s action in the main cardiovascular activities. Related to cardiovascular activities, ghrelin plays multitudinous beneficial and thereby help during cardiovascular diseases. Several studies demonstrated that ghrelin cause an anti-inflammatory activity by the inhibition of proinflammatory cytokines which can diminish inflammatory diseases in the heart, pericardium and specific innervations, for instance, vagus nerve and inhibited sympathetic nerves. Outcomes of this review emphasize these important actions of ghrelin. Methods: A systematic review of ghrelin activities over the heart and cardiovascular system with the inclusion of papers in review involved the physiological and physio pathological activities of ghrelin in vivo and in vitro studies. Results: Ghrelin is a natural tide with the growth hormone secretagogue (GHS) receptor (GHS-R) which cloned in 1996. The processes which generate this peptide and ghrelin-related peptides are transcriptional, translational and posttranslational. Homo and heterodimers of GHS-R and other yet unidentified receptors mediate the biological actions of acyl ghrelin and desacyl ghrelin. However, the main biological functions of ghrelin involve the secretion of growth hormone, stimulation of appetite and food intake at the hypothalamus, modulate acid secretion and motility, endocrine and exocrine pancreas secretion, blockaded insulin activity, heart functions and cardiovascular responses and other. Conclusion: One of the main occurrences in acute heart infarction is an increase activation of cardiac sympathetic nerve activity (CSNA) which is one of the causes of chronic cardiac dysfunction (CCD). Ghrelin is an effective for obtain a better cardiac function and by the suppression of renal sympathetic nerve activity which also have an important benefit to the acute myocardial infarction. Therefore, the physiological effects of ghrelin are very important to the body homeostasis even in the grave heart and cardiovascular diseases and in the immunological system.

Neuroimmune modulation mediated by IL-6: A potential target for the treatment of ischemia-induced ventricular arrhythmias

BackgroundNeural remodeling in the left stellate ganglion (LSG), as mediated by neuroimmune reactions, promotes cardiac sympathetic nerve activity (SNA) and thus increases the incidence of ventricular arrhythmias (VAs). Interleukin-6 (IL-6) is an important factor of the neuroimmune interaction. ObjectiveThe present study explored the effects of IL-6 on LSG hyperactivity and the incidence of VAs. MethodsEighteen beagles were randomly allocated to a control group (saline with myocardial infarction [MI], n = 6), adeno-associated virus (AAV) group (AAV with MI, n = 6), and IL-6 group (overexpression of IL-6 via AAV vector with MI, n = 6). Ambulatory electrocardiography was performed before and 30 days after AAV microinjection into the LSG. LSG function and ventricular electrophysiology were assessed at 31 days after surgery, and a canine MI model was established. Samples of the LSG were collected for immunofluorescence staining and molecular biological evaluation. Blood samples and 24-hour Holter data were obtained from 24 patients with acute MI on the day after they underwent percutaneous coronary intervention to assess the correlation between IL-6 levels and SNA. ResultsIL-6 overexpression increased cardiac SNA and worsened postinfarction VAs. Furthermore, sustained IL-6 overexpression enhanced LSG function, promoted expression of nerve growth factor, c-fos, and fos B in the LSG, and activated the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway. Clinical sample analysis revealed a correlation between serum IL-6 levels and heart rate variability frequency domain index as well as T-wave alternans. ConclusionIL-6 levels are correlated with cardiac SNA. Chronic overexpression of IL-6 mediates LSG neural remodeling through the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway, elevating the risk of VA after MI.

Machine learning based hybrid anomaly detection technique for automatic diagnosis of cardiovascular diseases using cardiac sympathetic nerve activity and electrocardiogram.

Coronary artery diseases (CADs) are the leading cause of death worldwide and early diagnosis is crucial for timely treatment. To address this, our study presents a novel automated Artificial Intelligence (AI)-based Hybrid Anomaly Detection (AIHAD) technique that combines various signal processing, feature extraction, supervised, and unsupervised machine learning methods. By jointly and simultaneously analyzing 12-lead cardiac sympathetic nerve activity (CSNA) and electrocardiogram (ECG) data, the automated AIHAD technique performs fast, early, and accurate diagnosis of CADs. In order to develop and evaluate the proposed automated AIHAD technique, we utilized the fully labeled STAFF III and PTBD databases, which contain the 12-lead wideband raw recordings non-invasively acquired from 260 subjects. Using these wideband raw recordings, we developed a signal processing technique that simultaneously detects the 12-lead CSNA and ECG signals of all subjects. Using the pre-processed 12-lead CSNA and ECG signals, we developed a time-domain feature extraction technique that extracts the statistical CSNA and ECG features critical for the reliable diagnosis of CADs. Using the extracted discriminative features, we developed a supervised classification technique based on Artificial Neural Networks (ANNs) that simultaneously detects anomalies in the 12-lead CSNA and ECG data. Furthermore, we developed an unsupervised clustering technique based on Gaussian mixture models (GMMs) and Neyman-Pearson criterion, which robustly detects outliers corresponding to CADs. Using the automated AIHAD technique, we have, for the first time, demonstrated a significant association between the increase in CSNA signals and anomalies in ECG signals during CADs. The AIHAD technique achieved highly reliable detection of CADs with a sensitivity of 98.48 %, specificity of 97.73 %, accuracy of 98.11 %, positive predictive value of 97.74 %, negative predictive value of 98.47 %, and F1-score of 98.11 %. Hence, the automated AIHAD technique demonstrates superior performance compared to the gold standard diagnostic test ECG in the diagnosis of CADs. Additionally, it outperforms other techniques developed in this study that separately utilize either only CSNA data or only ECG data. Therefore, it significantly increases the detection performance of CADs by taking advantage of the diversity in different data types and leveraging their strengths. Furthermore, its performance is comparatively better than that of most previously proposed machine and deep learning methods that exclusively used ECG data to diagnose or classify CADs. Additionally, it has a very low implementation time, which is highly desirable for real-time detection of CADs. The proposed automated AIHAD technique may serve as an efficient decision-support system to increase physicians' success in fast, early, and accurate diagnosis of CADs. It may be highly beneficial and valuable, particularly for asymptomatic patients, for whom the diagnostic information provided by ECG alone is not sufficient to reliably diagnose the disease. Hence, it may significantly improve patient outcomes by enabling timely treatments and considerably reducing the mortality of cardiovascular diseases (CVDs).

Autonomic Nerve Activity Features According to Dry Eye Type.

The purpose of this study was to investigate the association between autonomic nerve activity and symptom intensity according to the type of dry eye (DE). This prospective, cross-sectional, comparative study included 25 eyes of 25 patients with short tear break-up time DE (sBUTDE; mean age = 57.4 ± 11.4 years, range = 30-74 years) and 24 eyes of 24 patients with aqueous tear-deficient DE (ADDE; mean age = 62.3 ± 10.7 years, range = 29-76 years) were studied. Autonomic nerve activity was examined, and the Japanese version of the Ocular Surface Disease Index (J-OSDI) and a stress check questionnaire were administered. Autonomic nerve activity was continuously measured for 10 minutes. The parameters were low-frequency (LF) and high-frequency (HF) components of heart rate variability, reflecting cardiac sympathetic and parasympathetic nerve activity, and parasympathetic nerve activity alone, respectively; and the coefficient of variation of R wave-to-R wave (RR) interval (cvRR), component coefficient of variation of LF (ccvLF), and component coefficient of variation of HF (ccvHF), reflecting fluctuation of RR interval, LF, and HF, respectively. Higher J-OSDI scores were associated with higher HF, ccvHF, and subjective stress in sBUTDE, showing a significant correlation (r = 0.53, P < 0.01; r = 0.55, P = 0.01; and r = -0.66, P = 0.01); no correlations were observed between the J-OSDI score and autonomic parameters and stress in ADDE. DE symptoms were significantly associated with the magnitude and fluctuation of parasympathetic activity in sBUTDE. Thus, among the autonomic parameters, parasympathetic activity is involved in the development of symptoms in sBUTDE, whereas the involvement of the autonomic nervous system may be minimal in ADDE.

Pulmonary Artery Denervation Inhibits Left Stellate Ganglion Stimulation-Induced Ventricular Arrhythmias Originating From the RVOT

BackgroundElectrical stimulation of the left stellate ganglion (LSG) can evoke ventricular arrhythmias (VAs) that originate from the right ventricular outflow tract (RVOT). The involvement of pulmonary artery innervation is unclear. ObjectivesThis study investigated the effects of selective pulmonary artery denervation (PADN) on blood pressure (BP), sympathetic activity, ventricular effective refractory period (ERP), and the incidence of VAs induced by LSG stimulation in canines. MethodsRadiofrequency ablation with basic anesthetic monitoring was used to induce PADN in canines. In Protocol 1 (n = 11), heart rate variability, serum norepinephrine and angiotensin-II levels, BP changes and ventricular ERP in response to LSG stimulation were measured before and after PADN. In Protocol 2 (n = 8), the incidence of VAs induced by LSG stimulation was calculated before and after PADN in a canine model of complete atrioventricular block. In addition, sympathetic nerves in the excised pulmonary arteries were immunohistochemically stained with tyrosine hydroxylase. ResultsThe low-frequency components of heart rate variability, serum norepinephrine and angiotensin-II levels were remarkably decreased post-PADN. Systolic BP elevation and RVOT ERP shortening induced by LSG stimulation were mitigated by PADN. The number of RVOT-premature ventricular contractions as well as RVOT tachycardia episodes and duration induced by LSG stimulation were significantly reduced after PADN. In addition, a large number of tyrosine hydroxylase-immunoreactive nerve fibers were located in the anterior wall of the pulmonary artery. ConclusionsPADN ameliorated RVOT ERP shortening, and RVOT-VAs induced by LSG stimulation by inhibiting cardiac sympathetic nerve activity.

PC6 electroacupuncture reduces stress-induced autonomic and neuroendocrine responses in rats

Stress can trigger cardiovascular disease. Both imbalance of autonomic nervous activity and increase of neurohormonal output are core aspects of stress responses and can lead to cardiovascular disease. PC6 as a very important acupoint is used to prevent and treat cardiovascular disease and to improve stress-related activities. We examined the influence of electroacupuncture (EA) at PC6 on stress-induced imbalance of autonomic nervous activity and increase of neurohormonal output. EA at PC6 relieved increased cardiac sympathetic nervous activity and decreased cardiac vagal nervous activity induced by immobilization stress. Also, EA at PC6 reduced immobilization stress-induced increases of plasma norepinephrine (NE) and adrenaline (E) released from sympatho-adrenal-medullary axis. Finally, EA at PC6 reduced immobilization stress-induced increases of corticotropin-releasing hormone (CRH) in paraventricular hypothalamic nucleus and plasma cortisol (CORT) released from hypothalamic-pituitary-adrenal axis. However, EA at tail had no significant effect on the stress-induced autonomic and neuroendocrine responses. The results demonstrate the role of EA at PC6 regulating the autonomic and neuroendocrine responses induced by stress and provide insight into the prevention and treatment of EA at PC6 for stress-induced cardiovascular disease by targeting autonomic and neuroendocrine systems.

Early Effect of Transcatheter Mitral Valve Repair on Cardiac Sympathetic Nerve Activity

BackgroundCardiac sympathetic nerve activity (SNA) is overactivated in heart failure patients and associated with clinical outcomes. The aim of this study is to investigate the early effect of MitraClip repair on cardiac SNA. MethodsWe evaluated the change of cardiac SNA by 123I- meta-iodobenzylguanidine (MIBG) scintigraphy in patients who underwent MitraClip repair from March 2019 to June 2020 in our hospital. Patients without acute procedural success were excluded, including patients who died or underwent mitral valve surgery before discharge. MIBG scintigraphy was performed at baseline and 1 ​month after MitraClip repair. ResultsWe analyzed 48 patients (mean age 78.6 ± 10 years; 52.1% male; 37 secondary mitral regurgitation [SMR]/11 primary mitral regurgitation [PMR]). MR severity and New York Heart Association functional class significantly improved from baseline to 1 ​month after MitraClip repair (both p < 0.001). Overall, delay heart-mediastinum ratio (H/M) had no significant change, and washout rate (WR) showed a decreasing trend (delay H/M; pre 2.07 ± 0.46, post 2.05 ± 0.49, paired p = 0.348, WR; pre 36.1 ± 11.6%, post 33.6 ± 11.7%, paired p = 0.061). In PMR patients, WR was significantly decreased, however, delay H/M was not (delay H/M; pre 2.15 ± 0.50, post 2.10 ± 0.57, paired p = 0.019, WR; pre 34.6 ± 10.5%, post 26.7 ± 13.8%, paired p = 0.568). In contrast, in SMR patients, neither delay H/M nor WR were significantly changed (delay H/M; pre 2.05 ± 0.45, post 2.03 ± 0.47, paired p = 0.474, WR; pre 36.6 ± 11.9%, post 35.7 ± 10.4%, paired p = 0.523). ConclusionsOur study demonstrates that MitraClip repair could significantly decrease cardiac SNA of WR in PMR patients during 1-month follow-up, however, in SMR patients, the significant change of MIBG parameters was not observed.

LL-VNS attenuates SK2 expression and incidence of arrhythmias following acute myocardial infarction in rats.

Our previous study has demonstrated that low-level vagus nerve stimulation (LL-VNS) protects the heart against ventricular arrhythmias (VAs) induced by acute myocardial infarction (AMI). However, the potential mechanisms by which it influences ventricular electrophysiology remain unknown. Forty-five rats were divided into three groups: a Control group (sham AMI followed by sham LL-VNS, n = 15), an AMI group (AMI followed by sham LL-VSN for 60 mins, n = 15), and an AMI + LL-VNS group (AMI followed by LL-VSN for 60 mins, n = 15). Heart rate variability (HRV), ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT), and left stellate ganglion (LSG) activity were measured at baseline and during AMI. Finally, myocardial tissues were collected for tissue analysis. AMI directly induced hyperactivity in the LSG and reduced vagal tone as indexed by HRV. AMI also decreased VFT, and shortened ERP but increased ERP dispersion. AMI resulted in an increase in expression of ventricular small-conductance Ca2+-activated K+ (SK2). However, LL-VNS significantly mitigated or eliminated the effects of AMI. LL-VNS altered the electrophysiological properties of the ventricles through inhibition of cardiac sympathetic nervous activity and reduction in SK2 expression.

Assessment of the changes in cardiac sympathetic nervous activity using the pupil size changes measured in seated patients whose stellate ganglion is blocked by interscalene brachial plexus block.

As a side effect of interscalene brachial plexus block (ISBPB), stellate ganglion block (SGB) causes reductions in pupil size (Horner's syndrome) and cardiac sympathetic nervous activity (CSNA). Reduced CSNA is associated with hemodynamic instability when patients are seated. Therefore, instantaneous measurements of CSNA are important in seated patients presenting with Horner's syndrome. However, there are no effective tools to measure real-time CSNA intraoperatively. To evaluate the usefulness of pupillometry in measuring CSNA, we investigated the relationship between pupil size and CSNA. Forty-two patients undergoing right arthroscopic shoulder surgery under ISBPB were analyzed. Pupil diameters were measured at 30 Hz for 2 s using a portable pupillometer. Bilateral pupil diameters and CSNA (natural-log-transformed low-frequency power [0.04-0.15 Hz] of heart rate variability [lnLF]) were measured before ISBPB (pre-ISBPB) and 15 min after transition to the sitting position following ISBPB (post-sitting). Changes in the pupil diameter ([right pupil diameter for post-sitting - left pupil diameter for post-sitting] - [right pupil diameter for pre-ISBPB - left pupil diameter for pre-ISBPB]) and CSNA (lnLF for post-sitting - lnLF for pre-ISBPB) were calculated. Forty-one patients (97.6%) developed Horner's syndrome. Right pupil diameter and lnLF significantly decreased upon transition to sitting after ISBPB. In the linear regression model (R2 =0.242, P=0.001), a one-unit decrease (1 mm) in the extent of changes in the pupil diameter reduced the extent of changes in lnLF by 0.659 ln(ms2/Hz) (95% CI [0.090, 1.228]). Pupillometry is a useful tool to measure changes in CSNA after the transition to sitting following ISBPB.