Increased Vagal Tone Research Articles

Pilot Study of Weighted Blankets on Agitation.

BACKGROUND: Hospitalized patients who have had neurological trauma often require interventions to reduce agitation. Weighted blankets deliver deep pressure touch stimulation, which influences parasympathetic activity through increased vagal tone, to induce calmness and reduce sympathetic activation and reduction of the stress response. The purpose of this study was to investigate the effect of weighted blankets as an intervention on agitation scores in hospitalized adults who have experienced neurologic trauma. METHOD: This was a quasi-experimental design, pilot study with a convenience sample of patients who experienced neurological trauma. Participants who met the inclusion criteria received a weighted blanket that remained in place for 30 minutes. The Agitated Behavior Scale was used to measure the effect of the weighted blanket before and after the intervention with each participant serving as their own control. RESULTS: Twelve participants were included in the study. Related-samples Wilcoxon signed rank test indicated a significant difference for heart rate (P = .05) and Agitated Behavior Scale scores (P = .005). There were no significant differences with blood pressure or oxygen saturation levels. CONCLUSION: This pilot study demonstrated a reduction in agitation scores with the use of a weighted blanket. The deep pressure touch stimulation provided by a weighted blanket may provide a low-risk intervention to decrease agitation and prevent escalation. Future studies with larger sample sizes may demonstrate weighted blankets to decrease agitation and provide an adjunct therapy for patients.

Autonomic rehabilitation: Vagal and sympathetic impacts of modified occipitomastoid suture V-spread.

Autonomic rehabilitation using osteopathic manipulative treatment (OMT) to stimulate the vagus nerve may be a good adjunct therapy by physiatrists who treat dysautonomia. Heart rate variability (HRV) may provide quantitative evidence for the benefits of OMT on autonomic nervous system function. Elevated HRV indicates optimal health and reduced mortality risk, whereas low HRV is associated with stress, pain, and chronic disease pathology. To analyze the impact of modified occipitomastoid suture v-spread OMT technique on vagal tone by measuring HRV. Within-participant design with 5-minute HRV measurement pre- and post-OMT treatment. Clinical examination suites. Thirty healthy osteopathic medical students. A modified occipitomastoid suture v-spread treating somatic dysfunction by osteopathic physicians trained in osteopathic neuromusculoskeletal medicine. HRV variables related to vagal tone including root mean square of successive differences (RMSSD), percentage of successive normal sinus RR intervals >50 ms (pNN50), high frequency (HF), Parasympathetic Nervous System Index (PNSI), and Sympathetic Nervous System Index (SNSI). Repeated measures t-test analyzed the difference in mean HRV values after OMT. There were statistically significant increases in each of the HRV measures after OMT. Participants had a mean (95% confidence interval) RMSSD of 50.5 ms (38.3-62.8) at baseline and 55.0 ms (41.2-68.7, p = .013) post-OMT. pNN50 was 24.5% (17.6-31.3, n = 30) at baseline and 28.2% (20.8-35.6, p = .003) post-OMT. HF was 1549.6 ms2 (389.8-2709.4) at baseline and 1901.8 ms2 (618.2-3185.4, p = .103) post-OMT. PNSI was -0.1 (-0.5 to 0.2) at baseline and 0.1 (-0.3 to 1.5, p < .01) post-OMT, and SNSI was 0.2 (-0.1 to 0.6) at baseline and 0.05 (-0.3 to 0.4, p < .01) post-OMT. Normalization, due to high baseline variance, results include RMSSD 1.1 ms (1.0 to 1.1, p = .012), pNN50 1.3 (1.1 to 1.4, p = .011), and HF 1.2 ms2 (1.1 to 1.4, p = .018). Modified occipitomastoid suture v-spread may provide clinical benefit through increased vagal tone and decreased sympathetic activity.

Amelioration of social impairments in autism: Possible role of vagal afferent stimulation in modification of the prefrontal-amygdala connectivity

Impairment in social interactions is a prominent feature of autism spectrum disorder (ASD). The present hypothesis explains the possible role of vagal afferent stimulation in the modification of prefrontal-amygdala connectivity in the amelioration of social impairments in ASD. Currently, there is no definitive treatment for ASD. However, there is documented evidence showing that interventions that increase vagal tone lead to the improvement of autism-related social symptoms. However, the exact mechanism that explains the correlation between the elevation of vagal tone and the amelioration of autism-related symptoms has not been elucidated. In the present hypothesis, it is proposed that the increase in vagal tone affects the nucleus tractus solitarius (NTS) in the brainstem. The NTS has strong connections with other brainstem nuclei, such as the locus coeruleus and dorsal raphe nucleus. The aforementioned nuclei are the main sources of norepinephrine and serotonin, with extensive projections to various brain areas, especially the prefrontal cortex (PFC) and amygdala. PFC-amygdala functional connectivity plays an important role in social behavior and emotion regulation. Therefore, visceral stimulation, which subsequently increases the vagal tone, possibly leads to the improvement of autistic social deficits through the enhancement of PFC-amygdala functional connectivity. Further investigations are needed to evaluate the function of the mentioned neural pathways during visceral stimulation in individuals with ASD.

ECG screening and prevention of sudden cardiac death in endurance athletes over 40

Abstract Introduction CV diseases increase with age. There are many athletes aged &amp;gt;40 years who practise in certain endurance sports (marathon, ultramarathon and cycling), that involve very high intensity physical exertion and prolonged efforts. This population, like others athletes, undergo to annual examination with a medical history, spirometry, urine test and exercise test. CVdisease and sudden cardiac death (SCD) are the main cause of mortality in athletes during sport and this specific population group are at increased CV risk due to their multiple comorbidities, so this kind of screening remains controversial. Aims The primary aim of the study is to evaluate whether a 5-minute 'mini Holter ECG', associated with the conventional examination, can have an additional role for early screening and prevention of CV diseases in older endurance sport population. Materials The population were selected as part of the larger 'Heart And Run' project, an ECG collection of endurance athletes of the main sports clubs in Rome - Italy. A control group of healty individiuals was collected for comparison. The ECG traces were recorded at rest for 5 minutes with the Kardia Mobile device 6L™. HRV indices were analysed using the software Kubios. The study group were compared for an ECG morphological analysis and HRV parameters in the time and frequency domain. Results A total of 353 subjects (182 athletes, 171 controls) were analysed. The athlets show a significantly higher incidence of sinus arrhythmias, LAFB, 1°degree AVB, Jpoint elevation and STsegment abnormalities. We found also a significantly shorter QTc in athlets compared to controls (395.95 ± 29.51 ms vs. 411.6 ± 29.01 ms), suggestive of greater protection from malignant ventricular arrhythmias. In line with the ECG findings, the HRV PNS (-0.25 ± 1.25 vs -1.05 ± 1.45) and SNS (0.69 ± 1.44 vs 2.38 ± 1.89) indices were respectively higher and lower in the athletes group than in the controls group. Differences between the two groups were also found in the time and frequency HRV domain analysis (SDNN, RMSSD, NN50 and pNN50). Due to the absence of normality range, we considered values lower of the 5th or higher of the 95th percentile range, for the main HRV parameters, as abnormals. We identified 29/182 virtually abnormal HRV individuals. Those patients could be at increased CV risk, worthy of further investigation. In total, out-of-range HRV values or morphological abnormalities were detected in 54 athletes (29%), a population that will need further attention through follow-up and additional examinations. Conclusions Despite competitive endurance sports are associated with increased vagal tone, which is virtually protective against CV diseases, even in athletes over 40, the addition of the 5-minute cardiac 'mini Holter' could increase the sensitivity in detection of CV disease, in a specific high-risk group of athletes, suggesting additional clinical and instrumental investigations in such patients.

Do athletic ECG changes predict athletic performance in Gurkha recruits?

IntroductionECG changes are associated with regular long-term intensive exercise due to electrical manifestations of increased vagal tone, increased ventricular wall thickness and enlarged chamber size. The aim of this study...

Increased cardiac vagal tone in childhood-only, adolescent-only, and persistently antisocial teenagers: the mediating role of low heart rate.

Cardiac vagal tone is an indicator of parasympathetic nervous system functioning, and there is increasing interest in its relation to antisocial behavior. It is unclear however whether antisocial individuals are characterized by increased or decreased vagal tone, and whether increased vagal tone is the source of the low heart rate frequently reported in antisocial populations. Participants consisted of four groups of community-dwelling adolescent boys aged 15.7 years: (1) controls, (2) childhood-only antisocial, (3) adolescent-only antisocial, and (4) persistently antisocial. Heart rate and vagal tone were assessed in three different conditions: rest, cognitive stressor, and social stressor. All three antisocial groups had both lower resting heart rates and increased vagal tone compared to the low antisocial controls across all three conditions. Low heart rate partially mediated the relationship between vagal tone and antisocial behavior. Results indicate that increased vagal tone and reduced heart rate are relatively broad risk factors for different developmental forms of antisocial behavior. Findings are the first to implicate vagal tone as an explanatory factor in understanding heart rate - antisocial behavior relationships. Future experimental work using non-invasive vagus nerve stimulation or heart rate variability biofeedback is needed to more systematically evaluate this conclusion.

Abstract 16226: Stressed Out - When Sinus Bradycardia is Not Benign

Background Sinus bradycardia is often a benign and asymptomatic finding in athletes due to an increased vagal tone. However, when patients develop symptoms of decreased exercise tolerance, this warrants further investigation. We present a case of sinus bradycardia caused by adrenal insufficiency in a high-end athlete with exceptional physical reserve which resolved with treatment of the underlying cause and prevented unnecessary pacemaker implantation. Case Presentation A 44-year-old female athlete with no medical history who at baseline runs ultramarathons and weight lifts presented with severely symptomatic bradycardia. After initial recommendation of pacemaker placement during recent hospitalization, patient sought a second opinion. During her hospitalization, the patient underwent extensive work up including basic laboratory work, TSH, CT angiogram of the chest and TTE - all of which were found to be normal. She also had an exercise stress test and was only able to increase her HR to 50% of age-predicted rate. On further review, she was found to be hypothermic and reported menstrual irregularities, raising suspicion for endocrine abnormalities. Bradycardia, hypothermia and chronotropic incompetence prompted further workup which revealed a depressed cortisol with a low ACTH leading to a diagnosis of adrenal insufficiency. Further imaging revealed a pituitary microadenoma. The patient was referred to endocrinology and started therapy with steroids with resolution of her symptoms and is undergoing evaluation for surgical intervention. Conclusion Sinus bradycardia is a well-recognized occurrence in well trained athletes, caused by an increased vagal tone and is usually a benign finding. In our case, a patient underwent extensive work up for lightheadedness and exercise intolerance in the setting of her bradycardia which was unrevealing with initial recommendation of pacemaker placement. Upon further investigation, increased vagal tone alone was not responsible for severely symptomatic bradycardia and chronotropic incompetence. Notably, a combination of bradycardia, hypothermia, and irregular menses, resulted in work up revealing adrenal insufficiency, ultimately avoiding unnecessary pacemaker implant.

Atrioventricular Conduction: Physiology and Autonomic Influences.

Atrioventricular (AV) nodal conduction is decremental and very prone to alterations in autonomic tone. Conduction through the His-Purkinje system (HPS) is via fast channel tissue and typically not that dependent on autonomic perturbations. Applying these principles, when the sinus rate is stable and then heart block suddenly occurs preceded by even a subtle slowing of heart rate, it typically is caused by increased vagal tone, and block occurs in the AV node. Heart block with activity strongly suggests block in the HPS. Enhanced sympathetic tone and reduced vagal tone can facilitate induction of both AV and atrioventricular node reentry.

Typological Features of the Heart Rate Autonomic Regulation under Simulating a Rise to a Height by Using Additional Respiratory Resistance

The aim of this work was to study the indicators of heart rate variability (HRV) under conditions of additional respiratory resistance (ADR), as an imitation of climbing to a height, in young men with different types of autonomic regulation. The study involved 715 young men aged 19 to 24 years. HRV parameters were assessed by the method of variational pulsometry (BioMouse). Each subject passed two tests lasting 5 min: background, and under conditions of DDS. An ETM 2.0 resistive mask was used to simulate climbing (ADS simulation), in three altitudes: 3000, 9000, 18000 feet. Each person performed only one test; the height of the lift was not reported to him. Based on the results of background testing, two groups were created: the OB group – with balanced sympathetic and parasympathetic influences on HRV (stress index 25–100 c.u., VLF above 240 ms2), the PT group – with a moderate predominance of parasympathetic (vagal) influences (stress index below 25 c.u., VLF above 500 ms2). In the background testing, the OB group was characterized by higher values of the Bayevsky indices (IVR, VPR, PAPR), reflecting the predominance of sympathetic tone, and the PT group had higher values of the variation range of the duration of R–R intervals, RMSSD, SDNN, pNN50%, which are considered markers of increased vagal tone, and the total power of the HRV spectrum TP. Under conditions of ADR, without taking into account the height of the simulated rise, in the OB group, an increase in indicators correlated with vagal activity was revealed: the range of R–R intervals, RMSSD, SDNN, the HF range in the HRV spectrum, with a decrease in the Baevsky indices (IVR, VPR, PAPR, stress index). The increase in spectral measures of HRV associated with sympathetic activity (LF%) ant TP reached the level of statistical significance only when simulating an ascent to an altitude of 18 000 feet. In the PT group, the changes were oppositely directed: a decrease in correlates of vagal activity and an increase in sympathetic tone, regardless of the height of the lift. However, in both groups, the range of R–R intervals increased the most at 9000 feet, which is critical for the development of mountain sickness. Differences in the autonomic regulation of the cardiovascular system in young men determine the direction and severity of shifts in HRV indicators when simulating a rise to a height. In the OB group under conditions of ADR, when simulating a rise to insignificant heights, the indicators associated with vagal activity increase, with an increase in the height of the rise, an increase in parameters reflecting the sympathetic tone joins them. In the PT group, an expected increase in sympathetic tone was found at all altitudes.

Acceleration of postoperative recovery with brief intraoperative vagal nerve stimulation mediated via the autonomic mechanism.

Postoperative recovery is largely dependent on the restoration of gastrointestinal motility. The aim of this study was to investigate the effects and mechanisms of intraoperative vagus nerve stimulation (iVNS) on postoperative recovery from abdominal surgery in rats. The Nissen fundoplication surgery was performed on two groups of rats: sham-iVNS group and iVNS group (VNS was performed during surgery). Animal's behavior, eating, drinking and feces' conditions were monitored at specific postoperative days. Gastric slow waves (GSWs) and electrocardiogram (ECG) were recorded; blood samples were collected for the assessment of inflammatory cytokines. (1) iVNS shortened initiate times to water and food intake (p = 0.004) and increased the number of fecal pellets (p < 0.05, vs. sham-iVNS) and the percentage of water content in fecal pellets (p < 0.05). (2) iVNS improved gastric pace-making activity at 6 h after surgery reflected as a higher percentage of normal slow waves (p = 0.015, vs. sham-iVNS). (3) iVNS suppressed inflammatory cytokines at 24 h after surgery compared to sham-iVNS (TNF-α: p = 0.001; IL-1β: p = 0.037; IL-6: p = 0.002). (4) iVNS increased vagal tone compared to sham-iVNS group at 6 h and 24 h after the surgery (p < 0.05). Increased vagal tone was correlated with a faster postoperative recovery to start water and food intake. Brief iVNS accelerates postoperative recovery by ameliorating postoperative animal behaviors, improving gastrointestinal motility and inhibiting inflammatory cytokines mediated via the enhanced vagal tone.

Cardioneuroablation: Where are we at?

Since its original description in 2005, catheter ablation techniques, commonly called cardioneuroablation, have emerged as a potential strategy for modulating autonomic function. Multiple investigators have provided observational data on the potential benefits of this technique in a variety of conditions associated with or exacerbated by increased vagal tone such as vasovagal syncope, functional atrioventricular block, and sinus node dysfunction. Patient selection, current techniques including the various mapping strategies, clinical experience, and limitations of cardioablation are reviewed. Finally, while cardioneuroablation has potential to be a treatment option for selected patients with symptoms mediated by hypervagotonia, the document outlines the important knowledge gaps that currently exist and the necessary next steps required before this technique can be widely implemented into clinical practice.

Atrial Fibrillation in Endurance Training Athletes: Scoping Review.

Moderate regular physical activity is indicated to avoid atrial fibrillation (AF), whereas athletes should be counseled that long-lasting vigorous sports engagement may cause AF, according to the 2016 European Society of Cardiology (ESC) recommendations for AF treatment. Exercise and AF are complex. To evaluate the relationship between Endurance training and AF, in addition to the starting point/trigger by which Endurance Training causes impairment of cardiac function and AF, considering the time and intensity of Endurance training. We synthesized evidence from articles published in the PubMed, EMBASE, and SciELO databases using their respective Boolean operators. A total of 112 original articles related to AF and endurance athletes published up to the year 2023 were reviewed. Our study verified multiples aspects of the genesis of AF in athletes, such as cardiac adaptations to exercise, disturbances in cardiac injury biomarkers, sex differences in cardiac adaptations and their role in AF risk, and the relationship between body composition (height, weight, and physical fitness) and AF pathogenesis. Variations in cardiac structure (increased atrial thickness and size in addition to myocardial fibrosis) and significant increases in vagal tone (sinus bradycardia and imbalances in sympathetic and parasympathetic activation) shorten the refractory period shortening in athletes, induce the onset of re-entrance mechanisms, and serve as ectopic triggers that can lead to AF.

A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review.

In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.

PO-02-031 FEASIBILITY OF NONINVASIVE TRAGAL STIMULATION TO ASSESS VAGAL TONE DURING CARDIONEUROABLATION

There is increasing evidence that cardioneuroablation (CNA) can be an effective treatment for patients with atrial fibrillation and vasovagal syncope. The optimal procedural endpoint for CNA is unknown but elimination of response to invasive vagal stimulation has been utilized. To characterize the ability of transcutaneous tragal stimulation to non-invasively assess vagal tone before and after CNA as a potential procedural endpoint. We conducted a prospective, single center study in patients undergoing CNA as part of an ablation for atrial fibrillation. Transcutaneous tragal stimulation (left, right, then bilateral) was performed using Parasym vagal stimulator (20Hz, up to 42mA, up to 10 seconds) to identify vagal response. Positive response was defined as >2 seconds ventricular asystole, AV block or >10% increase in P-P or R-R interval. Stimulation was performed at baseline and repeated immediately following the CNA portion of the procedure. Among 19 patients, 9(47%) were male, median age was 70.7 years (IQR 66.9-70.7), median CHA2DS2Vasc score was 3(IQR 2.5-4). Atrial fibrillation was paroxysmal in 13 patients (68%), 11 patients (58%) were on antiarrhythmic therapy and 6 patients (32%) had prior ablations for atrial fibrillation. Response to bilateral stimulation was noted in 2 patients and only to left tragal stimulation in 1 patient. The response in these patients was a median increase in the PP interval by 350ms (IQR 310 – 370) or 31% (IQR 29 – 44) without an increase in the PR interval noted in any patient. No response to stimulation was seen after CNA in these 3 patients. Among all patients, median heart rate (HR) increase after CNA was 19 bpm (IQR 14-36, p=0.0001) and the PR interval decreased by a median of 15ms (IQR 9.5-41, p=0.0024). Changes in HR and PR interval was seen in both patients with tragal stimulation response (HR increase median 26 bpm and PR decrease median 36ms) and without response to tragal stimulation (HR increase median 15 bpm and PR decrease median 14 ms). High output tragal stimulation was inconsistently able to produce identifiable increase in vagal tone. When identified, elimination of response may be a reliable indicator of effective CNA, however the low response rate limits its utility. The poor efficacy observed may be due to the limited tragal innervation of the vagus nerve and alternative stimulation sites, such as the auditory canal should be considered.Tabled 1Table 1Baseline Characteristicsn=19Age (years) median (IQR)70.7 years (67-73.3)Male gender n (%)9 (47%)Prior historyHypertension n (%)14 (73%)Obstructive Sleep Apnea n (%)4 (21%)Diabetes n (%)5 (26%)Congestive Heart Failure n (%)3 (15%)Coronary artery disease n (%)7 (37%)Cerebrovascular disease n (%)1 (5%)Peripheral arterial disease n (%)2 (10%)CHA2DS2Vasc median (IQR)3 (2.5-4)Atrial Fibrillation detailsParoxysmal n (%)13 (69%)Persistent n (%)6 (32%)Vagally mediated AF n (%)8 (42%)Coexisting Atrial Flutter n (%)6 (32%)Antiarrhythmic drugs11 (58%)Prior ablation n (%)6 (32%)Echocardiographic featuresLeft Ventricular Ejection Fraction (%) median (%)60 (55-65)Normal Left atrial size n (%)4 (21%)Severe Left atrial dilatation n (%)1 (5%)Tragal Stimulation responseLeft tragal response n (%)1 (5%)Bilateral tragal response n (%)2 (10%)ΔPP interval pre-ablation (msec) median (IQR)350ms (IQR 310 – 370)Post Cardioneuroablation responseΔHeart rate post-ablation (bpm) median (IQR)18.5bpm (IQR 13.5 to 35.5)ΔPR interval post-ablation (msec) median (IQR)-15ms (IQR -9.5 to -41) Open table in a new tab

239 VASOSPASTIC ANGINA: A CASE OF COMPLETE FUNCTIONAL ASSESSMENT

Abstract Introduction Vasospastic angina is defined as a focal or diffuse spasm of the arterial wall of an epicardial coronary artery due to muscle cells hyperreactivity caused by an increased calcium sensitivity. Clinical presentation typically consists in chronic story of rest and/or effort typical chest pain, episodes of ST elevated or not ST elevated myocardial infarction, arrhythmias or cardiac arrest; an increased vagal tone, drugs, allergic reactions or the exposure to extreme cold also can trigger vasospasm. Clinical case 73 years old dyslipidemic woman; in past medical history thyroidectomy and radiotherapy for carcinoma and right quadrantectomy with radiotherapy and hormonal therapy for breast cancer. In 2017 admission to cath-lab for non-ST elevation myocardial infarction (NSTEMI) with the evidence of mild left coronary artery disease without critical obstructive stenosis (MINOCA). For the persisting of effort angina and dyspnea (NYHA and CCS II-III), started Diltiazem therapy (60 mg x3) with clinical benefit. In 2020, due to the onset of new episodes of angina, started Ranolazine therapy. In June 2022, for the worsening of clinical symptoms, was evaluated with a Coronary CT, that showed a 65% stenosis at right coronary-acute marginal bifurcation and mild disease on left coronary artery, and then was admitted for an elective coronary angiography, with no evidence of epicardial artery critical stenosis. At the functional evaluation FFR, CFR and IMR (&amp;gt;0.80, 2.5 and 18) demonstrated normal coronary flow reserve and good microcirculation function. For the suspicion of vasospastic angina, acetylcholine test was performed with the evidence of mid-distal left anterior descending artery total occlusion, angina onset and ECG changes, promptly regressed with nitrates administration (Figure 1). Patient was discharged with the optimization of medical therapy with Diltiazem 120 mg x3, with clinical benefit. Conclusions To date vasospastic angina remains underdiagnosed. Functional evaluation of coronary arteries plays a fundamental role in the diagnostic algorithm of the disease and should always be investigated in case of patients with typical symptoms and the absence of critical epicardial stenosis. Further investigations are required to better explain pathogenesis and to identify affected patients in shorter times to ensure early optimized medical therapy.

Autonomic nerve regulation in joint hypermobility patients with myofascial trigger points by Musculoskeletal Interfiber Counterirritant Stimulation (MICS).

Joint hypermobility (JH) conditions suggest dysfunction in the autonomic nervous system (ANS) (dysautonomia), associated with multifactor non-articular local musculoskeletal pain, and remains a complex treatment. This study aims to determine the effects of musculoskeletal interfiber counterirritant stimulation (MICS) as an innovative treatment of myofascial trigger points (MTrPs) on the upper trapezius muscle in JH patients. We evaluate the ANS activity by wavelet transform spectral analysis of heart rate variability (HRV) in sixty women, equally divided: MTrP, MTrP+general joint hypermobility (GJH), and MTrP+joint hypermobility syndrome (JHS). The protocol phases were rest, stimulation, and recovery, with clinical and home treatment for three-days. All groups show a significantly decreased in pain perception during and post-treatment, and an increased parasympathetic ANS activity under MICS in the GJH and JHS groups. The variables low-frequency (LF) vs. high-frequency (HF) showed significant differences during the protocol phases, and the LF/HF ratio maintained a predominance of sympathetic activity (SA) throughout the protocol. The new MICS technique reduces the pain perception and modulates the ANS activity by an increase in vagal tone, and a decrease in sympathetic tone. This modulation was followed by an increase in the HRV in JH patients after treatment with MICS. Clinical Trials: RBR-88z25c5.

Reversible QRS fragmentation in Takotsubo cardiomyopathy.

An 80-year-old lady with a history of diabetes mellitus presented to the emergency room with palpitations. Electrocardiogram revealed ST-segment elevation over the inferior and lateral leads. Notably, the QRS complexes across precordial leads V4-6 and aVR were fragmented. A positive deflection was seen in lead V1, embedded within the QRS complex, which is resemblant to the Epsilon wave morphology (Figure 1, left columns). Despite such findings and raised serum troponin, she was free from chest pain. Transthoracic echocardiography showed left ventricular (LV) apical ballooning with severe hypokinesis, corroborated by invasive left ventriculography. Coronary angiography revealed no occlusive lesion. The diagnosis was Takotsubo cardiomyopathy (TTC). (Figure 2). The finding of fragmented QRS in TTC is of electrophysiological interest. Arrhythmic manifestations complicating TTC affects up to one-quarter of patients, and half is life-threatening (13.5%).1 Symptomatic atrioventricular block and less commonly sinus nodal dysfunction may mandate cardiac pacing and are due to a secondary increase in vagal tone in sympathetic overdrive. The origin of ventricular tachycardia (VT)/ fibrillation remained controversial in TTC. While QT prolongation is well-recognized in TTC that provided a substrate for polymorphic VT, the origin of monomorphic VT was believed to be catecholaminergic or automatic, and unlikely reentrant based on classical lack of myocardial fibrosis detectable as late gadolinium MRI enhancement in TCC.2, 3 However, latest research provided revoking evidence by identifying diffuse fibrosis/ micronecrosis through T1-mapping in TTC.4 QRS fragmentation, a marker of myocardial fibrosis, is predictive of sudden cardiac death in patients with ischemic and non-ischemic cardiomyopathy. Its presence in the inferior leads, in particular, was identified as an ominous sign in patients with known cardiomyopathy for subsequent sudden death,5 while lateral lead predominance conferred excess risks in subjects without structural heart disease. Whether fragmented QRS has a prognostic role in Takotsubo cardiomyopathy remained unclear. Furthermore, myocardial edema during a hyperacute phase in TTC may predispose to transient electrical inhomogeneity.2 On the contrary, the Epilson wave, an electrocardiographic finding characteristic of arrhythmogenic right ventricular cardiomyopathy, together with QRS fragmentation are both indicators of delayed ventricular depolarization. While the Epilson wave has been reported in myocarditis, how it is related to myocardial edema in the hyperacute phase of TTC and whether it may have a prognostic role remained obscure. In our patient, no significant nodal dysfunction or ventricular tachyarrhythmia occurred. She was treated with aspirin (80 mg daily), lisinopril (2.5 mg daily), bisoprolol fumarate (1.25 mg daily), and atorvastatin (20 mg daily). Three months later, reassessment echocardiography showed recovered LV systolic function with an ejection fraction of 65%, and resolution of apical ballooning. These were accompanied by a complete reversal of QRS fragmentation and the disappearance of the Epsilon wave-like morphology (Figure 1, rights columns). Ambulatory Holter assessment showed nil evidence of electrical instability. This succinct Spotlight thus re-capitulates the fundamental electro-pathophysiological basis implicated in the natural course of TTC, in which further research is needed. Li Shu Fan Medical Fellowship for Internal Medicine 2021/22 (Y.H.C.) None declared.

Pathophysiology and Management of Neurogenic Pulmonary Edema in Patients with Acute Severe Brain Injury.

Acute brain injury (ABI) consists of any acquired insult to the brain and is a significant cause of morbidity and mortality worldwide. Approximately 20% to 30% of patients with ABI develop a lung injury called neurogenic pulmonary edema (NPE), and its development often results in poor outcomes. This article provides a narrative review of the evidence regarding proposed mechanisms of injury, diagnosis, and treatment of NPE in the critical care setting. PubMed and Ovid databases were searched for observational or prospective studies relevant to the diagnosis and treatment of NPE. Overall, studies showed that although the specific mechanisms responsible for NPE remain uncertain, putative mechanisms include vaso- and venoconstriction, catecholamine release with resultant pulmonary vasoconstriction called the "blast injury theory," increased vagal tone, and increased capillary permeability. Diagnosis involves identifying signs of pulmonary edema in patients who experienced a neurologic insult. Management strategies aim to address both brain and lung injury, and treatment modalities appear to work best when balanced toward maintaining a normal physiologic state. In summary, NPE is an often underdiagnosed but important sequela of ABI, which may result in additional long-term morbidity. It is therefore an important entity for providers to recognize and tailor their clinical approach toward.

Forebrain corticosteroid receptors promote post-myocardial infarction depression and mortality

Myocardial infarction (MI) with subsequent depression is associated with increased cardiac mortality. Impaired central mineralocorticoid (MR) and glucocorticoid receptor (GR) equilibrium has been suggested as a key mechanism in the pathogenesis of human depression. Here, we investigate if deficient central MR/GR signaling is causative for a poor outcome after MI in mice. Mice with an inducible forebrain-specific MR/GR knockout (MR/GR-KO) underwent baseline and follow-up echocardiography every 2 weeks after MI or sham operation. Behavioral testing at 4 weeks confirmed significant depressive-like behavior and, strikingly, a higher mortality after MI, while cardiac function and myocardial damage remained unaffected. Telemetry revealed cardiac autonomic imbalance with marked bradycardia and ventricular tachycardia (VT) upon MI in MR/GR-KO. Mechanistically, we found a higher responsiveness to atropine, pointing to impaired parasympathetic tone of ‘depressive’ mice after MI. Serum corticosterone levels were increased but—in line with the higher vagal tone—plasma and cardiac catecholamines were decreased. MR/GR deficiency in the forebrain led to significant depressive-like behavior and a higher mortality after MI. This was accompanied by increased vagal tone, depleted catecholaminergic compensatory capacity and VTs. Thus, limbic MR/GR disequilibrium may contribute to the impaired outcome of depressive patients after MI and possibly explain the lack of anti-depressive treatment benefit.

Paradoxical worsening of bradycardia following atropine administration.

Bradyarrhythmias are a common entity in both emergency and out-of-hospital (OOH) medicine. In unstable bradycardic patients, paramedics will often initiate life-saving therapies in the OOH setting. Clinical guidelines for bradyarrhythmias are largely consistent across the globe, with intravenous (IV) atropine recommended as a first-line therapy, escalating to IV adrenaline or isoprenaline and transcutaneous pacing where atropine is unsuccessful. In this case report, we describe a case in the OOH setting of ventricular standstill following the administration of atropine to a patient with bradycardia and 2:1 heart block. The patient was a 77-year-old female presenting with a symptomatic 2:1 heart block. Following a single dose of 600 micrograms IV atropine, the patient deteriorated into ventricular standstill with a loss of consciousness and decorticate posturing. The patient was successfully managed with an IV infusion of adrenaline and subsequently received an implanted pacemaker in hospital. The paradoxical worsening of this patient's bradycardia following atropine administration may have been related to the location of the heart block. It has been shown that patients with atrioventricular blocks at the level of the His-Purkinje fibres (infranodal) are at an increased risk of adverse events following atropine administration, while those at the nodal level or secondary to increased vagal tone are more likely to respond favourably. Paramedics should be prepared to manage unexpected adverse events secondary to atropine administration in patients with heart block.