Exposure to individual polycyclic aromatic compounds impairs the cardiac performance of American lobster (Homarus americanus) larvae.

The potential for oil spills poses a threat to marine organisms, the toxicity of which has been attributed primarily to polycyclic aromatic compounds (PACs). Predictive tools such as the target lipid model (TLM) have been developed to forecast and assess these risks. The aim of the present study was to characterize the cardiotoxicity of 10 structurally diverse PACs in American lobster (Homarus americanus) larvae by assessing heart rate following a 48 h exposure in a passive dosing system, and subsequently use the TLM framework to calculate a critical target lipid body burden (CTLBB) for bradycardia. Exposure to 8 of the 10 PACs resulted in concentration-dependent bradycardia, with phenanthrene causing the greatest effect. The TLM was able to effectively characterize bradycardia in American lobsters, and the cardiotoxic CTLBB value determined in this study is among the most sensitive endpoints included in the CTLBB database. This study is one of the first to apply the TLM to a cardiac endpoint and will improve predictive models for assessing sublethal impacts of oil spills on American lobster populations.

Chemo- and optogenetic activation of hypothalamic Foxb1-expressing neurons and their terminal endings in the rostral-dorsolateral PAG leads to tachypnea, bradycardia, and immobility.

Foxb1 -expressing neurons occur in the dorsal premammillary nucleus (PMd) and further rostrally in the parvafox nucleus, a longitudinal cluster of neurons in the lateral hypothalamus of rodents. The descending projection of these Foxb1+ neurons end in the dorsolateral part of the periaqueductal gray (dlPAG). The functional role of the Foxb1+ neuronal subpopulation in the PMd and the parvafox nucleus remains elusive. In this study, the activity of the Foxb1+ neurons and of their terminal endings in the dlPAG in mice was selectively altered by employing chemo- and optogenetic tools. Our results show that in whole-body barometric plethysmography, hM3Dq-mediated, global Foxb1+ neuron excitation activates respiration. Time-resolved optogenetic gain-of-function manipulation of the terminal endings of Foxb1+ neurons in the rostral third of the dlPAG leads to abrupt immobility and bradycardia. Chemogenetic activation of Foxb1+ cell bodies and ChR2-mediated excitation of their axonal endings in the dlPAG led to a phenotypical presentation congruent with a 'freezing-like' situation during innate defensive behavior.

Effects of Esketamine Combined with Propofol for Hysteroscopy Anesthesia on Patient Hemodynamics and Adverse Reactions.

Objective: To investigate the effect of esketamine combined with propofol on patient hemodynamics and its safety in hysteroscopy anesthesia. Methods: A total of 186 hysteroscopic patients admitted to our hospital from January 2021 to January 2022 were selected, and the patients were divided into group K and Group P according to a completely random number table, with 93 cases each. In short, all patients are uniformly numbered and adequately intermixed, according to the prescribed sampling starting point and order, the sample unit numbers were successively drawn from the random number table, until the extraction to the required sample size. Group K was given esketamine combined with propofol intravenously, and group P was given sufentanil combined with propofol intravenously. The changes in respiratory circulation [heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (SpO2)] at the time of entering the operating room (T0), at the beginning of surgery (T1), 10 minutes after surgery(T2), and 10 minutes after the end of surgery (T3) were compared between the two groups, as well as the total time of surgery, the time to wake up after surgery, the amount of propofol used intraoperatively and the proportion of additional propofol were compared. The numerical rating scale (NRS) was used to assess the pain level of patients in both groups at different times after awakening and the occurrence of intraoperative and postoperative adverse reactions such as body movement, respiratory depression, bradycardia, injection site pain, nausea and vomiting, and dizziness were counted in both groups. Results: There were no significant changes in MAP, HR, and SpO2 in Group K at all moments compared with T0 (P > .05), MAP, HR and SpO2 in Group P at T1 and T2 were lower than those at T0 (P < .05). MAP, HR, and SpO2 were significantly lower in Group P at T1 and T2 moments compared with Group K, suggesting that circulatory depression was more pronounced in Group P at T1 and T2 moments (P < .05) and was not conducive to postoperative recovery. Compared with group P, the postoperative recovery time of group K was significantly shorter, and the dosage of propofol and the proportion of additional propofol were significantly lower (P < .05) which was beneficial to the health of patients. The pain level was significantly lower in Group K at 5, 15, and 30 minutes after awakening than in Group P (P < .05). The incidence of adverse reactions such as intraoperative motion, respiratory depression, bradycardia, injection site pain, and dizziness was significantly lower in group K than in group P (P < .05), and there was no significant difference in the incidence of nausea and vomiting between the two groups (P > .05), and prove that esketamine combined with propofol used for anesthesia which have high safety as well as more effective. Conclusion: The use of esketamine compounded with propofol in hysteroscopy anesthesia has less effect on the patient's circulatory and respiratory systems. This protocol can improve the postoperative analgesic effect of anesthesia in patients, reduce the amount of propofol during surgery, have fewer adverse effects and mild symptoms, is safe and effective, and can be used in clinical practice.

Mechanism of Lingbao Huxin Dan in the treatment of bradyarrhythmia complicated with coronary heart disease: a network pharmacology analysis.

OBJECTIVE: To investigate the mechanism of action of the Lingbao Huxin Dan in treating bradycardia arrhythmia with coronary heart disease (BA-CHD) by network pharmacology. METHODS: The active ingredients of the Lingbao Huxin Dan were screened on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Bioinformatics tools designed for the analysis of molecular mechanisms of Chinese medicine platform; target prediction was conducted with the SwissTargetPrediction database, and Cytoscape 3.8 was used to construct a drug ingredient-target network. The Genecards, Online Mendelian Inheritance in Man, and DrugBank databases were searched for disease targets. Venn plots were used to display the common targets of BA-CHD and active ingredients. The STRING platform was used to construct a protein-protein interaction network. The Metascape data platform was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to construct a signaling pathway network of the active ingredients of the Lingbao Huxin Dan. RESULTS: There were 121 active ingredients, 899 related targets, 39 targets important in BA-CHD and 14 targets which intersected between the active ingredients and BA-CHD. There were 27 core therapeutic ingredients, 153 biological processes, 18 cell ingredients and 20 molecular functions obtained by GO enrichment analysis. The KEGG pathway analysis yielded 19 signaling pathways. CONCLUSION: RBA-CHD may treat BA-CHD by regulating adrenergic receptor beta-1, alpha 1-α adrenergic receptor, calcium voltage-gated channel subunit alpha1 C, alpha-1ß-adrenergic receptor, nitric oxide synthase 2, beta-2 adrenergic receptor, voltage-dependent calcium channel subunit alpha-2/delta-1, an- giotensin-converting enzyme, Raf-1 proto-oncogene serine/threonine-protein kinase, and other targets, potentially by affecting adrenergic receptor binding and calcium channel opening, to regulate the activity of cardiomyocytes.

High-dose IV magnesium in mesothelioma patients receiving surgery with hyperthermic intraoperative cisplatin: Pilot studies and design of a phase II randomized clinical trial.

INTRODUCTION: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans. METHODS: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B. RESULTS: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium. CONCLUSIONS: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.

Toxic Tetrahydrocannabinol (THC) Dose in Pediatric Cannabis Edible Ingestions.

OBJECTIVE: The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions. METHODS: This is a retrospective review of children aged <6 years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015-October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses. RESULTS: Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8-4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6-6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%). CONCLUSIONS: The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.

Facilitated extinction but impaired extinction recall by eye movement manipulation in humans - Indications for action mechanisms and the applicability of eye movement desensitization.

Eye movement desensitization and reprocessing (EMDR) therapy utilizes the manipulation of eye movements to reduce affective distress during fear-exposure. Animal research recently suggested a potential neural mechanism underlying these effects, by which increased activity of the superior colliculus (SC), mediating visual attention, increases the inhibition of the basolateral amygdala (BLA), mediating defensive plasticity. We tested such mechanism in forty healthy humans using a multiple-day single-cue fear conditioning and extinction paradigm. The activity of the SC during extinction was experimentally manipulated by eye movements, as half of the participants executed saccadic eye movements (n = 20; major SC involvement), while the other half executed smooth eye pursuits (n = 20; minor SC involvement). Amygdala-mediated fear-potentiated startle responses and fear bradycardia, as well as threat expectancy was analyzed. Saccadic eye movements facilitated the extinction of fear bradycardia and fear-potentiated startle responses. Higher saccadic accuracy and range correlated with reduced fear-potentiated startle. However, during extinction recall, fear-potentiated startle and fear bradycardia resurged and partly reached levels obtained after fear acquisition. Threat expectancy was not affected by different eye movements and was not elevated during extinction recall. Within limitations, results support an inhibitory SC-BLA pathway in humans by which eye movements may reduce low-level defensive responding, but not threat expectancy. Yet, manipulating eye movements during extinction learning seems to impair extinction recall for behavioral and physiological defensive response indices. Thus, increasing SC activity might enhance initial efficacy of exposure treatment, but additional strategies seem necessary for sustained fear attenuation.

Acupuncture Treatment of a Patient with Bradycardia and Idioventricular Rhythm.

A patient with bradycardia and an idioventricular rhythm was observed. According to cardiologists, there is no reliable drug treatment for bradycardia with an idioventricular rhythm; instead, the sole treatment is a pacemaker. In the course of this case, it was shown that acupuncture can restore the heart rhythm from bradycardia to normocardia, and from idioventricular with third-degree atrioventricular node block and an average heart rate of 34 BPM, to normal sinus rhythm with a heart rate of 71 BPM. Additionally, at the end of the treatment, the patient's number of episodes of ventricular extrasystole decreased 36 times (3289 versus 91 episodes). These results show that research on this technique should be continued.

Analysis of prescription medication rules of traditional Chinese medicine for bradyarrhythmia treatment based on data mining.

BACKGROUND: Multiple studies have revealed that Traditional Chinese Medicine (TCM) prescriptions can provide protective effect on the cardiovascular system, increase the heart rate and relieve the symptoms of patients with bradyarrhythmia. In China, the TCM treatment of bradyarrhythmia is very common, which is also an effective complementary therapy. In order to further understand the application of Chinese medicines in bradyarrhythmia, we analyzed the medication rules of TCM prescriptions for bradyarrhythmia by data mining methods based on previous clinical studies. METHODS: We searched studies reporting the clinical effect of TCM on bradyarrhythmia in the PubMed and Chinese databases China National Knowledge Infrastructure database, and estimated publication bias by risk of bias tools ROB 2. Descriptive analysis, hierarchical clustering analysis and association rule analysis based on Apriori algorithm were carried out by Microsoft Excel, SPSS Modeler, SPSS Statistics and Rstidio, respectively. Association rules, co-occurrence and clustering among Chinese medicines were found. RESULTS: A total of 48 studies were included in our study. Among the total 99 kinds of Chinese medicines, 22 high-frequency herbs were included. Four new prescriptions were obtained by hierarchical cluster analysis. 81 association rules were found based on association rule analysis, and a core prescription was intuitively based on the grouping matrix of the top 15 association rules (based on confidence level), of which Guizhi, Zhigancao, Wuweizi, Chuanxiong, Danshen, Danggui, Huangqi, Maidong, Dangshen, Rougui were the most strongly correlated herbs and in the core position. CONCLUSION: In this study, data mining strategy was applied to explore the TCM prescription for the treatment of bradyarrhythmia, and high-frequency herbs and core prescription were found. The core prescription was in line with the treatment ideas of TCM for bradyarrhythmia, which could intervene the disease from different aspects and adjust the patient's Qi, blood, Yin and Yang, so as to achieve the purpose of treatment.

HIGH-DOSE INSULIN EUGLYCEMIC THERAPY.

Calcium channel blockers and beta-blockers toxicity/poisoning are one of the most common causes of poisoning. More importantly, they are among the deadliest types of poisoning caused by cardiac drugs that emergency physicians can encounter. Common toxidrome caused by these medications includes the following symptoms: hypotension, bradycardia, hypoglycemia/hyperglycemia, hypothermia, arrhythmia, and seizures. Treatment is usually complex, It consists of administration of various medications, such as crystalloids, intravenous calcium, glucagon, vasopressors/inotropes, and especially high-dose insulin euglycemic therapy. In this paper, we will review the mechanism for this type of treatment, propose a potential protocol for its application and address possible adverse effects. High-dose insulin euglycemic therapy should be an integral part of the treatment protocol for calcium channel blockers and beta-blockers toxicity.

Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome.

BACKGROUND: Mice with deletion of complex I subunit Ndufs4 develop mitochondrial encephalomyopathy resembling Leigh syndrome (LS). The metabolic derangement and underlying mechanisms of cardio-encephalomyopathy in LS remains incompletely understood. METHODS: We performed echocardiography, electrophysiology, confocal microscopy, metabolic and molecular/morphometric analysis of the mice lacking Ndufs4. HEK293 cells, human iPS cells-derived cardiomyocytes and neurons were used to determine the mechanistic role of mitochondrial complex I deficiency. RESULTS: LS mice develop severe cardiac bradyarrhythmia and diastolic dysfunction. Human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) with Ndufs4 deletion recapitulate LS cardiomyopathy. Mechanistically, we demonstrate a direct link between complex I deficiency, decreased intracellular (nicotinamide adenine dinucleotide) NAD+ /NADH and bradyarrhythmia, mediated by hyperacetylation of the cardiac sodium channel NaV 1.5, particularly at K1479 site. Neuronal apoptosis in the cerebellar and midbrain regions in LS mice was associated with hyperacetylation of p53 and activation of microglia. Targeted metabolomics revealed increases in several amino acids and citric acid cycle intermediates, likely due to impairment of NAD+ -dependent dehydrogenases, and a substantial decrease in reduced Glutathione (GSH). Metabolic rescue by nicotinamide riboside (NR) supplementation increased intracellular NAD+ / NADH, restored metabolic derangement, reversed protein hyperacetylation through NAD+ -dependent Sirtuin deacetylase, and ameliorated cardiomyopathic phenotypes, concomitant with improvement of NaV 1.5 current and SERCA2a function measured by Ca2+ -transients. NR also attenuated neuronal apoptosis and microglial activation in the LS brain and human iPS-derived neurons with Ndufs4 deletion. CONCLUSIONS: Our study reveals direct mechanistic explanations of the observed cardiac bradyarrhythmia, diastolic dysfunction and neuronal apoptosis in mouse and human induced pluripotent stem cells (iPSC) models of LS.

Hyperoxia and the cardiovascular system: experiences with hyperbaric oxygen therapy.

Hyperoxia has been described to induce bradycardia by direct stimulation of the parasympathetic nervous system. Also, hyperoxia has been found to increase blood pressure by an elevation of vascular resistance. However, the latter effect itself would induce bradycardia by baroreceptor stimulation. This single-arm monocentric retrospective study aims to evaluate the correlation between these effects by investigating the relation between oxygen (O2) administration and heart rate over time. Data were collected from 23 patients without cardiovascular problems undergoing hyperbaric oxygen therapy (2.4 bar) retrospectively. During single oxygen bouts, transcutaneously measured partial pressure of O2 was increased. During this surge of oxygen pressure, the arterial blood pressure was increased while the heart rate was decreased. Respiration rate was maintained independently from breathing 100% O2 or air. During single oxygen bouts, the half-life of transcutaneously measured partial pressure of O2 was 5.4 ± 2.1 mmHg/s, and the half-life of heart rate was 0.45 ± 0.19 beats/min. It has been shown that hyperbaric oxygen therapy increases the transcutaneously measured partial pressure of O2. This increase was rather fast, followed by a rather slow decrease in HR. This finding does not support direct vagal activation. Heart rate is not decreased due to a direct vagal activation during hyperbaric oxygen therapy. Our single-arm, retrospective study has additionally confirmed that oxidative stress injures the endothelium, and the reduced endothelial-derived vasodilators cause vasoconstriction. As a consequence, blood pressure increases, and heart rate is then further decreased via the baroreceptor reflex.

Atribuições do enfermeiro no manejo do marcapasso transcutâneo em pacientes idosos: Uma revisão integrativa / Asignaciones del enfermero em el manejo del marcapasos transcutáneo en anciano: Una revisión integrativa / Nurse attributions in the handling of transcutaneous pacemaker in elderly patients: Integrative review

Objetivo: investigar a produção científica nacional e internacional sobre as ações e cuidados do enfermeiro no manejo do marca-passo transcutâneo em idosos. Método: revisão integrativa, realizada nas bases de dados "Scopus", "Web of Science", "EMBASE", "PUBMED", "MEDLINE", no período de 2012 a 2022. Resultados: foram selecionados oito artigos, todos internacionais, somente um conduzido por enfermeiros. Categorizados por: (1) Possibilidades e limitações no uso do marca-passo trânscutâneo na prática clínica; (2) Cuidados de enfermagem na utilização do marca-passo transcutâneo em idosos e (3) Sistematização da Assistência de Enfermagem e a abordagem ao paciente em uso de marca-passo transcutâneo. Conclusão: os principais cuidados de enfermagem ao idoso que utiliza o marca-passo transcutâneo são: prevenção de queimaduras cutâneas; administração de medicamentos; manejo da dor; monitoramento dos dados vitais; avaliação da captura mecânica; investigação do histórico familiar; medicações em uso; realização do exame físico e acesso venoso periférico.(AU)

Objective: : to investigate the national and international scientific production regarding the actions and handling of the transcutaneous pacemaker in elderly. Method: integrative review, made in the databases Scopus", "Web of Science", "EMBASE", "PUBMED", and "MEDLINE", for the period 2012 to 2022. Findings: there were selected eight articles, all international, and only one conducted by nurses. Categorized into: (1) Possibilities and limitations of the use from the transcutaneous pacemaker in clinical practice; (2) Nursing care when utilizing transcutaneous pacemaker in elderly and (3) Systematization of Nursing Care and approach to patients using transcutaneous pacemaker. Conclusion: the main Nursing Care approaches to elderly who use transcutaneous pacemaker are prevent skin burn; drug administration; pain management; monitoring vital signs; evaluation of heart activity; investigating family history and drugs in use; performing physical examination and peripheral venous access.(AU)

Objetivo: investigar cual és lá produccion científica nacional e internacional sobre Las acciones y cuidados del enfermero en el manejo del marca-pado intracutaneo en ancianos. Método: Revision Integrativa realizada en Las bases de datos "Scopus" web of Science", EMBASE", "PUBMED", "MEDLINE", durante el período 2012 a 2022. Resultados: fueron Seleccionados ocho articulos todos internacionales, solanemente uno fue llevado a cabo por enfermeros. Categorizado por (1) posibilidades y limitaciones en El uso del marca-paso intracutaneo en lá práctica clínica; (2) cuidados de enfermeria en lá utilização del marca-paso intracutaneo y (3) sistematizacion de la assistencia de enfermeria y el abordaje del paciente que usa marca-paso intracutaneo. Conclusion: Los principales cuidados de enfermeria Al anciano que utiliza marca-paso intracutaneo son: prevencion de quemaduras cutaneas; administracion de medicamentos, manejo del dolor, monitorizacion de datos vitales, evaluacion de lá captura mecanica, investigação del histórico famíliar, medicaciones en uso, realizacion de examen fisico y acceso venoso periférico.(AU)

His bundle pacing: A promising alternative strategy for anti-bradycardic pacing - report of a single-center experience.

His bundle pacing (HBP) is proven to be a safe and effective alternative pacing modality that, in addition, avoids pacemaker-induced cardiomyopathy (PICM) by achieving a "physiological" ventricular stimulation, via the native conduction system. Indications include various causes of bradycardia requiring anti-bradycardic pacing, inadequately controlled atrial fibrillation requiring AV node ablation and established PICM. In addition, HBP may also be used as an alternative therapy for patients with heart failure (HF) and an indication for cardiac resynchronization therapy (CRT). Available data show several advantages of HBP with regard to preservation or restoration of intra- and inter-ventricular synchronization; improvement in left ventricular ejection fraction, functional status and quality of life; decrease in atrial fibrillation incidence and improvement in HF hospitalization rates, compared with conventional pacing. Nevertheless, superiority in terms of mortality rates has not been consistently demonstrated, and the long-term efficacy and safety of HBP remain to be proven. In the present manuscript, we review the status of HBP and present our current experience with this novel pacing modality.

Mechanism of Datura metel on sinus bradycardia based on network pharmacology and molecular docking.

OBJECTIVE: To investigate the mechanism of action of Datura metel in the treatment of sinus bradycardia based on network pharmacology and molecular docking. METHODS: The active ingredients and targets of Datura metel were collected by TCMSP database, and the Cytoscape software was used to map to show the interrelationship. Use 5 databases: GeneCards, PharmGKB, OMIM, DisGeNET, and Drugbank to obtain targets related to sinus bradycardia; establish a protein-to-protein interaction network with the help of the STRING platform; GO and Kyoto Encyclopedia of Genes and Genomes analysis of the selected core targets using the Metascape platform; Finally, the AutoDock platform was used for molecular docking and the results were displayed through Pymol. RESULTS: 27 kinds of active ingredients of the drug were screened, including 10 kinds of main ingredients; 198 drug targets and 1059 disease targets. There are 54 targets of action in the treatment of sinus bradycardia, of which 19 targets such as AKT1, IL6, TNF, and VEGFA are the core targets of Datura metel in the treatment of sinus bradycardia. Kyoto Encyclopedia of Genes and Genomes obtained 18 results suggesting that AGE-RAGE, hepatitis C, relaxin, and JAK-STAT may be key signaling pathways. Molecular docking shows that most components of the drug have good docking ability with the core target, indicating that the prediction results have certain reliability. CONCLUSION: This study preliminarily explores the potential active ingredients and possible mechanisms of action of Datura metel in the treatment of sinus bradycardia and provides a basis for in-depth investigation of its medicinal material basis and mechanism of action.

[Systematic review and Meta-analysis of efficacy and safety of Yangxin Dingji Capsules in treatment of arrhythmia].

To systematically review the efficacy and safety of Yangxin Dingji Capsules in the treatment of arrhythmia. PubMed, EMbase, Cochrane Library, CNKI, VIP, CBM and Wanfang databases were electronically retrieved to collect randomized controlled trial(RCT) on the efficacy of Yangxin Dingji Capsules in the treatment of arrhythmia from the time of database establishment to October 20 th, 2020. Two reviewers independently screened out the literatures, input the data, and evaluated the literature quality of the included studies. RevMan 5.3 software was used for Meta-analysis. A total of 127 studies were retrieved, and 15 articles were included after screening, involving 1 371 cases, with 685 cases in the treatment group and 686 cases in the control group. Yangxin Dingji Capsules combined with anti-arrhythmia western medicine was adopted for intervention in the treatment group, while the patients in the control group were treated with the anti-arrhythmia western medicine alone. Meta-analysis results showed that in arrhythmia patients, the combination of Yangxin Dingji Capsules and conventional western medicine significantly increased the clinical efficacy(RR=1.23, 95%CI[1.17, 1.30], P<0.000 01)and left ventricular ejection fraction(MD=4.31, 95%CI[3.10, 5.52], P<0.000 01), reduced heart rate(MD=-3.79, 95%CI[-7.42,-0.15], P=0.04), left ventricular end-diastolic diameter(MD=-7.06, 95%CI[-11.91,-2.21],P=0.004), left ventricular end-systolic diameter(MD=-4.78, 95%CI[-6.63,-2.93],P<0.000 01), N-terminal B-type natriuretic peptide precursor(MD=-200.51, 95%CI[-254.52,-146.51], P<0.000 01)and high-sensitivity C-reactive protein(MD=-1.74, 95%CI[-3.23,-0.24], P=0.02), all with statistically significant differences. Compared with the control group, Yangxin Dingji Capsules had fewer adverse reactions(RR=0.53, 95%CI[0.36, 0.79], P=0.002). The existing evidences showed that Yangxin Dingji Capsules had certain effect in the treatment of arrhythmia, with a safety. However, due to the limitation in sample size, outcome measures and quality of the included studies, more high-quality studies are required to verify the above conclusion.

Defensive freezing and its relation to approach-avoidance decision-making under threat.

Successful responding to acutely threatening situations requires adequate approach-avoidance decisions. However, it is unclear how threat-induced states-like freezing-related bradycardia-impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach-avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia (high-vs-low threat) interacted with subjective value, depending on the action-context (passive-vs-active). Specifically, in action-contexts incongruent with participants' intrinsic action-tendencies, stronger bradycardia related to diminished effects of subjective value on choice across participants. These findings illustrate the relevance of testing approach-avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach-avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporating internal psychophysiological states and external action-contexts into models of approach-avoidance decision-making.

Attentive immobility in the face of inevitable distal threat-Startle potentiation and fear bradycardia as an index of emotion and attention.

During fear conditioning, a cue (CS) signals an inevitable distal threat (US) and evokes a conditioned response that can be described as attentive immobility (freezing). The organism remains motionless and monitors the source of danger while startle responses are potentiated, indicating a state of defensive hypervigilance. Although in animals vagally mediated fear bradycardia is also reliably observed under such circumstances, results are mixed in human fear conditioning. Using a single-cue fear conditioning and extinction protocol, we tested cardiac reactivity and startle potentiation indexing low-level defensive strategies in a fear-conditioned (n = 40; paired presentations of CS and US) compared with a non-conditioned control group (n = 40; unpaired presentations of CS and US). Additionally, we assessed shock expectancy ratings on a trial-by-trial basis indexing declarative knowledge of the previous contingencies. Half of each group underwent extinction under sham or active transcutaneous vagus nerve stimulation (tVNS), serving as additional proof of concept. We found stronger cardiac deceleration during CS presentation in the fear learning relative to the control group. This learned fear bradycardia was positively correlated with conditioned startle potentiation but not with declarative knowledge of CS-US contingencies. TVNS abolished differences in heart rate changes between both groups and removed the significant correlation between late cardiac deceleration and startle potentiation in the fear learning group. Results suggest, fear-conditioned cues evoke attentive immobility in humans, characterized by cardiac deceleration and startle potentiation. Such defensive response pattern is elicited by cues predicting inevitable distal threat and resembles conditioned fear responses observed in rodents.

[Systematic review and Meta-analysis of efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia].

To systematically evaluate the efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia by Meta-analysis. Randomized controlled trial(RCT) or quasi-randomized control trial(Quasi-RCT) on Ningxinbao Capsules treating arrhythmia were obtained by computer-based retrieval in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and EMbase as well as manual retrieval, with time limit from database establishment to April 7, 2020. According to the inclusion and exclusion criteria of trials, all RCTs were screened and evaluated. Then the effective data were collected and RevMan 5.3 Meta-analysis software was used for analysis. Thirteen trials were included, involving 1 379 patients in total. Ningxinbao Capsules combined with anti-arrhythmia Western medicine were adopted as the intervention, and the patients in control group were treated with the anti-arrhythmia Western medicine alone. Meta-analysis results showed that as compared to control group, Ningxinbao Capsules combined with anti-arrhythmia Western medicine group was superior in clinical efficacy, dynamic electrocardiogram and average heart rate in patients with bradycardia, with indicated statistically significant differences. Ningxinbao Capsules had fewer adverse reactions and could relieve the toxic and side effects of anti-arrhythmia medicine possibly. The study showed that Ningxinbao Capsules played a role in treatment of arrhythmia and was relatively safe. However, due to the limited quality of the included studies, high-quality clinical trials are needed to verify the conclusions.

Low-dose steroid-induced bradyarrhythmias and treatment refractory hypokalaemia: a case report.

Corticosteroid therapy has become an important modality of treatment for diseases in which rapid control of immunoinflammatory processes is required. However, one of the serious, but less known adverse effect of this therapy is cardiac arrhythmias. This includes both tachyarrhythmias and bradyarrhythmias. Corticosteroid use may also be associated with electrolyte imbalances like hypokalaemia by its mineralocorticoid activity. Those side effects are mainly seen with high-dose intravenous methyl-prednisolone or oral pulse dose prednisolone therapy. Here we report our experience in a child with warm idiopathic autoimmune haemolytic anaemia who developed sinus bradyarrhythmias and treatment refractory hypokalaemia during low-dose steroid therapy with reduction in heart rate by 60% of baseline.