articles+ search results

medicine.medical_specialty, Angiotensin receptor, Diastole, Tetrazoles, Angiotensin-Converting Enzyme Inhibitors, Context (language use), 030204 cardiovascular system & hematology, Sacubitril, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, cardiovascular diseases, 030212 general & internal medicine, Systole, Heart Failure, Receptors, Angiotensin, Ejection fraction, business.industry, Arrhythmias, Cardiac, Stroke Volume, medicine.disease, Treatment Outcome, Valsartan, Heart failure, cardiovascular system, Cardiology, Neprilysin, Rabbits, Cardiology and Cardiovascular Medicine, business, and medicine.drug

Background The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. Methods New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. Results HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. Conclusions In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.

Adult, Male, medicine.medical_specialty, Adolescent, Taiwan, Sudden cardiac death, Electrocardiography, Young Adult, Deep Learning, Rare Diseases, Cohen's kappa, Internal medicine, medicine, Humans, Diagnosis, Computer-Assisted, cardiovascular diseases, Medical diagnosis, Brugada Syndrome, Retrospective Studies, Brugada syndrome, business.industry, Incidence, Deep learning, Middle Aged, Right bundle branch block, medicine.disease, Feature (computer vision), Cohort, Cardiology, Female, Artificial intelligence, Cardiology and Cardiovascular Medicine, business, and Follow-Up Studies

Background Brugada syndrome is a major cause of sudden cardiac death in young people with a distinctive electrocardiogram (ECG) feature. We aimed to develop a deep learning-enabled ECG model for automatic screening Brugada syndrome to identify these patients at an early time, thus allowing for life-saving therapy. Methods A total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for one to one allocation) were extracted from the hospital-based ECG database for a two-stage analysis with a deep learning model. After trained network for identifying right bundle branch block pattern, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared to that of board-certified practicing cardiologists. The model was further validated in the independent ECG dataset, collected from the hospitals in Taiwan and Japan. Results The diagnoses by the deep learning model (AUC: 0.96, sensitivity: 88.4%, specificity: 89.1%) were highly consistent with the standard diagnoses (Kappa coefficient: 0.78). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (Kappa coefficient: 0.63). In the independent ECG cohort, the deep learning model still reached a satisfactory diagnostic performance (AUC 0.89, sensitivity: 86.0%, specificity: 90.0%). Conclusions We presented the first deep learning-enabled ECG model for diagnosing Brugada syndrome, which appears to be a robust screening tool with a diagnostic potential rivaling trained physicians.

0301 basic medicine, MAPK/ERK pathway, MAP Kinase Signaling System, p38 mitogen-activated protein kinases, Anti-Inflammatory Agents, Stimulation, 030204 cardiovascular system & hematology, Pharmacology, Electrocardiography, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucosides, Phenols, Fibrosis, NLR Family, Pyrin Domain-Containing 3 Protein, Rhodiola, Animals, Medicine, Pharmacology (medical), RNA, Messenger, Chemokine CCL20, Dose-Response Relationship, Drug, biology, business.industry, Interleukin-17, Salidroside, Arrhythmias, Cardiac, General Medicine, medicine.disease, biology.organism_classification, CD4 Lymphocyte Count, Disease Models, Animal, Drug Combinations, 030104 developmental biology, chemistry, Apoptosis, Rabbits, Interleukin 17, Inflammation Mediators, Cardiology and Cardiovascular Medicine, business, and Signal Transduction

Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model. Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4+ T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation. After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4+ T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated. RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.

0301 basic medicine, medicine.medical_specialty, Physiology, Clinical Biochemistry, Pilsicainide, Contractility, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sodium channel blocker, Physiology (medical), Internal medicine, medicine, Repolarization, Receptor, Pacing - action, business.industry, 030104 developmental biology, chemistry, Pinacidil, cardiovascular system, Cardiology, Potassium channel opener, business, 030217 neurology & neurosurgery, and medicine.drug

Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker). There were 15 (9.9%) inducible VT episodes (group 1) and 136 (90.1%) non-inducible VT episodes (group 2) in our tissue model. Group 1 had greater post-pacing increases of the first occurrence of AP at 90% repolarization (ΔAPD90, p 15% and a ΔContractility > 270%, but were undetectable in those with a ΔAPD90 < 15% and a ΔContractility < 270%. In those with pacing-induced VTs, KB-R7943 (10 μM, a Na+-Ca2+ exchanger inhibitor, NCX inhibitor) significantly reduced the occurrence of VTs from 100.0 to 20.0% (15/15 to 3/15 episodes, p < 0.001). Concurrent increases in both post-pacing APD and contractility resulted in the occurrence of ventricular arrhythmias. NCX inhibition may be a potential therapeutic strategy for ventricular arrhythmias.

Male, Phenylurea Compounds, Pinacidil, Action Potentials, Lidocaine, Tetrazoles, Heart, Myocardial Contraction, Heart Rate, Tachycardia, Ventricular, Animals, Rabbits, Anti-Arrhythmia Agents, and Sodium Channel Blockers

Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker). There were 15 (9.9%) inducible VT episodes (group 1) and 136 (90.1%) non-inducible VT episodes (group 2) in our tissue model. Group 1 had greater post-pacing increases of the first occurrence of AP at 90% repolarization (ΔAPD

Pulmonary Arterial Hypertension, Monocrotaline, Endothelin-1, Organic Chemistry, Arrhythmias, Cardiac, General Medicine, Pulmonary Artery, Catalysis, Computer Science Applications, Inorganic Chemistry, Disease Models, Animal, Connexin 43, Animals, Familial Primary Pulmonary Hypertension, pulmonary arterial hypertension, atrial arrhythmogenesis, Rabbits, Physical and Theoretical Chemistry, Molecular Biology, Proto-Oncogene Proteins c-akt, and Spectroscopy

Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN–RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1/ET-A receptor/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias.

medicine.medical_specialty, Patch-Clamp Techniques, Heart Ventricles, chemistry.chemical_element, Action Potentials, Calcium, Ventricular tachycardia, urologic and male genital diseases, Electrocardiography, right ventricular outflow tract, Internal medicine, medicine, Ventricular outflow tract, Myocyte, Animals, Humans, Myocytes, Cardiac, Patch clamp, Renal Insufficiency, Chronic, Calcium metabolism, calcium homeostasis, business.industry, Arrhythmias, Cardiac, Cell Biology, Original Articles, medicine.disease, Immunohistochemistry, Disease Models, Animal, Oxidative Stress, Sarcoplasmic Reticulum, chemistry, Heart Function Tests, Cardiology, Molecular Medicine, Original Article, ventricular tachycardia, Disease Susceptibility, Rabbits, business, chronic kidney disease, Biomarkers, Low sodium, and Kidney disease

Chronic kidney disease (CKD) increases the risk of arrhythmia. The right ventricular outflow tract (RVOT) is a crucial site of ventricular tachycardia (VT) origination. We hypothesize that CKD increases RVOT arrhythmogenesis through its effects on calcium dysregulation. We analysed measurements obtained using conventional microelectrodes, patch clamp, confocal microscopy, western blotting, immunohistochemical examination and lipid peroxidation for both control and CKD (induced by 150 mg/kg neomycin and 500 mg/kg cefazolin daily) rabbit RVOT tissues or cardiomyocytes. The RVOT of CKD rabbits exhibited a short action potential duration, high incidence of tachypacing (20 Hz)‐induced sustained VT, and long duration of isoproterenol and tachypacing‐induced sustained and non‐sustained VT. Tachypacing‐induced sustained and non‐sustained VT in isoproterenol‐treated CKD RVOT tissues were attenuated by KB‐R7943 and partially inhibited by KN93 and H89. The CKD RVOT myocytes had high levels of phosphorylated CaMKII and PKA, and an increased expression of tyrosine hydroxylase‐positive neural density. The CKD RVOT myocytes exhibited large levels of I to, I Kr, NCX and L‐type calcium currents, calcium leak and malondialdehyde but low sodium current, SERCA2a activity and SR calcium content. The RVOT in CKD with oxidative stress and autonomic neuron hyperactivity exhibited calcium handling abnormalities, which contributed to the induction of VT.