Alectinib causes sinus bradycardia by suppressing L-type calcium current in sinus node

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177527 - 177527

Опубликована: Март 1, 2025

Язык: Английский

---

Heart Rate Reduction Is Associated With Reverse Left Ventricular Remodeling and Mechanism-Specific Molecular Phenotypes in Dilated Cardiomyopathy

Circulation Heart Failure, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Heart rate (HR) affects heart failure outcomes, via uncertain mechanisms that may include left ventricular remodeling. However, in human myocardium, HR change has not been associated with a particular remodeling molecular phenotype. Patients nonischemic dilated cardiomyopathy (N=22) sinus rhythm and refractory to β-blockade for both lowering reverse were randomized 2:1 double-blind the HCN4 (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4) inhibitor ivabradine or placebo 24 weeks treatment while maintaining target doses of β-blockers. Reverse was measured by ejection fraction (LVEF), myocardial gene expression sequencing RNA extracted from endomyocardial biopsies. The primary statistical analysis between categories divided at median, which resulted Decreased (N=90) Unchanged (N=8) groups. Respective HRs baseline as follows: HR, 82.9±6.8 69.7±8.0 beats per minute (P=0.0005) 80.8±5.7 79.2±11.6 (P=0.58). All completing subjects treated ivabradine, whereas group, 3 received 5 placebo. In LVEF increased 29.4±8.8% 44.2±9.4% (P=0.0003), compared respective values 26.6±11.4% 29.2±12.0% (P=0.28) HR. changes different previously conducted β-blocker study subdivided into responders nonresponders. differentially expressed genes (N=151) versus groups >99% nonconcordant therefore individually unique HR/LVEF nonresponders (2 shared genes). Multiple including NRG1 upregulation are considered cardioprotective involved cardiac development. patients rhythm, se (1) is substantial remodeling; (2) its absence can cause nonresponse; (3) when inhibition, results URL: https://www.clinicaltrials.gov; Unique identifier: NCT02973594.

Язык: Английский

---

Occupational stress as a risk factor for cardiovascular accidents in medical staff of anesthesiology and intensive care units (review)

Messenger of Anesthesiology and Resuscitation, Год журнала: 2025, Номер 22(2), С. 139 - 148

Опубликована: Апрель 16, 2025

Introduction. Occupational stress is one of the most common causes cardiovascular catastrophe among emergency response personnel. The objective was to analyze literature sources on assessing level and its impact health indicators in medical staff anesthesiology intensive care units. Materials methods . analysis included 70 publications from PubMed e-library abstract databases for period 2017 2023. search carried out using keywords: professional burnout syndrome, stress, personality, anesthesiologist-resuscitator, unit, heart rate variability, provider anesthesiologist, physician, rhythm variability. After a primary examination abstracts, 20 articles were excluded review as there lack access full text or they devoted organizational prevention activities Results. It has been demonstrated that long working day more than 10 years associated with an increase likelihood developing coronary disease (CHD), especially men. A linear risk recurrent CHD attacks established time 40 hours week four after myocardial infarction. revealed severe occupational decrease HRV due parasympathetic influences. In resident anesthesiologists, maximum inhibition variability noted at stage induction anesthesia eve night watch. Conclusion. long-term sympathetic activity autonomic nervous system suppression impulses indicate high probability diseases stress.

Язык: Английский

---

Identification of atrial fibrillation-related genes through transcriptome data analysis and Mendelian randomization

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Июль 11, 2024

Background Atrial fibrillation (AF) is a common persistent arrhythmia characterized by rapid and chaotic atrial electrical activity, potentially leading to severe complications such as thromboembolism, heart failure, stroke, significantly affecting patient quality of life safety. As the global population ages, prevalence AF on rise, placing considerable strains individuals healthcare systems. This study utilizes bioinformatics Mendelian Randomization (MR) analyze transcriptome data genome-wide association (GWAS) summary statistics, aiming identify biomarkers causally associated with explore their potential pathogenic pathways. Methods We obtained microarray datasets GSE41177 GSE79768 from Gene Expression Omnibus (GEO) database, merged them, corrected for batch effects pinpoint differentially expressed genes (DEGs). gathered exposure expression quantitative trait loci (eQTL) outcome GWAS through IEU Open database. employed inverse variance weighting (IVW), MR-Egger, weighted median, model approaches MR analysis assess exposure-outcome causality. IVW was primary method, supplemented other techniques. The robustness our results evaluated using Cochran's Q test, MR-Egger intercept, MR-PRESSO, leave-one-out sensitivity analysis. A “Veen” diagram visualized overlap DEGs significant eQTL analysis, referred (CGs). Additional analyses, including Ontology (GO) enrichment, Kyoto Encyclopedia Genes Genomes (KEGG) pathways, immune cell infiltration studies, were conducted these intersecting reveal roles in pathogenesis. Results combined dataset revealed 355 (DEGs), 228 showing upregulation 127 downregulated. randomization identified that autocrine motility factor receptor (AMFR) [IVW: OR = 0.977; 95% CI, 0.956–0.998; P 0.030], leucine aminopeptidase 3 (LAP3) 0.967; 0.934–0.997; 0.048], Rab acceptor 1 (RABAC1) 0.928; 0.875–0.985; 0.015], tryptase beta 2 (TPSB2) 0.971; 0.943–0.999; 0.049] are reduced risk (AF). Conversely, GTPase-activating SH3 domain-binding protein (G3BP2) 1.030; 1.004–1.056; 0.024], integrin subunit (ITGB2) 1.050; 1.017–1.084; 0.003], glutaminyl-peptide cyclotransferase (QPCT) 1.080; 1.010–0.997; 1.154], tripartite motif containing 22 (TRIM22) 1.048; 1.003–1.095; 0.035] positively risk. Sensitivity analyses indicated lack heterogeneity or horizontal pleiotropy ( > 0.05), did not any single nucleotide polymorphisms (SNPs) impacting significantly. GO KEGG showed CG involved processes polyubiquitination, neutrophil degranulation, specific tertiary granule formation, protein-macromolecule adaptor molecular SREBP signaling pathway, all enriched. demonstrated associations various cells, plasma CD8T resting memory CD4T regulatory T cells (Tregs), gamma delta activated NK mast neutrophils. Conclusion By integrating approaches, AMFR, G3BP2, ITGB2, LAP3, QPCT, RABAC1, TPSB2, TRIM22 linked AF, enhancing understanding its foundations. strategy may facilitate development more precise therapeutic targets diagnosis treatment.

Язык: Английский

---

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

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Сен. 12, 2024

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

Язык: Английский

---

The Role of HCN4 Variants in Human Systolic Heart Failure and Protein Interaction Network

Salud Ciencia y Tecnología, Год журнала: 2024, Номер 5, С. 1101 - 1101

Опубликована: Дек. 5, 2024

Introduction: An elevated heart rate (HR) results in adverse outcomes human systolic failure with a sinus rhythm. Genetic variants may alter HCN4 interactions regulatory proteins and increase HR. This study aimed to generate protein interaction network (PIN) associated HR determine gene (718G>A, 1571G>A, 2648C>G) patients failure, rhythm, heart. Methods: STRING database was used PIN. Laboratory exploration performed identify using PCR DNA sequencing. Results: PIN revealed eight nodes 13 edges. functional enrichment showed the essential (ADRB1 HCN channels) involved regulation. GNAS ADCY1 contributed regulation process. properties of channel. scores protein-protein that HCN4, ADRB1, GNAS, were high (in range 0.879-0.979). The three evaluated 49 participants HR≥70 bpm after 10 mg bisoprolol therapy. However, only 718G>A identified patients. Conclusion: channels elevating ADCY1. Only found out increased HR, according laboratory investigation on

Язык: Английский

---

Impact of the Coronavirus Disease 2019 [COVID-19] Pandemic on Post-Acute Care of Patients with Heart Failure and the Effectiveness of Vaccine Prevention

Healthcare, Год журнала: 2024, Номер 12(21), С. 2171 - 2171

Опубликована: Окт. 31, 2024

The Heart Failure Post-Acute Care [HF-PAC] program is a specialized healthcare aimed at providing comprehensive care and support for patients with heart failure [HF] as they transition from acute hospital settings to home. But the impact of coronavirus disease 2019 [COVID-19] pandemic on HF-PAC remains unknown. Furthermore, effects COVID-19 vaccination these warrants further investigation.

Язык: Английский

---

Cardiac Pacemaker Cells Harness Stochastic Resonance to Ensure Fail-Safe Operation at Low Rates Bordering on Sinus Arrest

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 20, 2024

ABSTRACT BACKGROUND The sinoatrial node (SAN) is primary pacemaker of the heart. Recent high-resolution imaging showed that synchronized action potentials (APs) exit SAN emerge from heterogeneous signals, including subthreshold signals in non-firing (dormant) cells. This sets up a new problem cardiac biology how these contribute to heartbeat generation. Here we tested hypothesis cells harness stochastic resonance ensure their fail-safe operation, especially at low rates bordering on sinus arrest. METHODS We measured membrane potential and Ca isolated rabbit hearts response external currents form sine waves or white noise. Protocols were applied via perforated patch while either basal state presence cholinergic receptor stimulation. Additionally, performed multiscale model simulations respective sub-cellular, cellular, tissue levels. RESULTS Noise awakened dormant fire APs substantially improved rate rhythm firing infrequent, dysrhythmic APs. Rhythmic AP generation applications wave different frequencies outlined spectrum cells: capability responding, resonance, specific frequency components embedded Cholinergic stimulation shifted towards lower frequencies, i.e. responded but could not process higher signals. added single cell– tissue-models expanded parametric space beyond bifurcation line where failed operate without Both numerical models our simultaneous recordings dynamics also demonstrated amplified by coupled electrical signaling, enhancing noise CONCLUSIONS membrane-Ca signaling rhythmic initiation rates, providing last-resort mechanism avoid arrest when signal synchronization decreases increases, such as during strong parasympathetic stimulation, disease aging heart slows high-frequency wanes.

Язык: Английский

---