Hormones and sex differences: changes in cardiac electrophysiology with pregnancy

2016 ◽  
Vol 130 (10) ◽  
pp. 747-759 ◽  
Author(s):  
Glenna C.L. Bett
Keyword(s):  
Postpartum Period ◽  
Cardiac Electrophysiology ◽  
Delayed Rectifier ◽  
Hormonal Changes ◽  
Large Variability ◽  
Early Symptom ◽  
Cardiac Electrical Activity ◽  
Channel Expression ◽  
Electrocardiogram Ecg ◽  
Ionic Basis

Disruption of cardiac electrical activity resulting in palpitations and syncope is often an early symptom of pregnancy. Pregnancy is a time of dramatic and dynamic physiological and hormonal changes during which numerous demands are placed on the heart. These changes result in electrical remodelling which can be detected as changes in the electrocardiogram (ECG). This gestational remodelling is a very under-researched area. There are no systematic large studies powered to determine changes in the ECG from pre-pregnancy, through gestation, and into the postpartum period. The large variability between patients and the dynamic nature of pregnancy hampers interpretation of smaller studies, but some facts are consistent. Gestational cardiac hypertrophy and a physical shift of the heart contribute to changes in the ECG. There are also electrical changes such as an increased heart rate and lengthening of the QT interval. There is an increased susceptibility to arrhythmias during pregnancy and the postpartum period. Some changes in the ECG are clearly the result of changes in ion channel expression and behaviour, but little is known about the ionic basis for this electrical remodelling. Most information comes from animal models, and implicates changes in the delayed-rectifier channels. However, it is likely that there are additional roles for sodium channels as well as changes in calcium homoeostasis. The changes in the electrical profile of the heart during pregnancy and the postpartum period have clear implications for the safety of pregnant women, but the field remains relatively undeveloped.

scholarly journals Co-expression of calcium channels and delayed rectifier potassium channels protects the heart from proarrhythmic events

2019 ◽  
Author(s):  
Sara Ballouz ◽  
Melissa M Mangala ◽  
Matthew D Perry ◽  
Stewart Heitmann ◽  
Jesse A Gillis ◽  
...  
Keyword(s):  
Ion Channel ◽  
Cardiac Electrophysiology ◽  
Meta Analysis ◽  
Surrogate Marker ◽  
Induced Pluripotent Stem Cell ◽  
Delayed Rectifier ◽  
Cardiac Electrical Activity ◽  
Channel Expression ◽  
Induced Pluripotent ◽  
Electrical Signaling

AbstractCardiac electrical activity is controlled by the carefully orchestrated activity of more than a dozen different ion conductances. Yet, there is considerable variability in cardiac ion channel expression levels both within and between subjects. In this study we tested the hypothesis that variations in ion channel expression between individuals are not random but rather there are modules of co-expressed genes and that these modules make electrical signaling in the heart more robust.Meta-analysis of 3653 public RNA-Seq datasets identified a strong correlation between expression of CACNA1C (L-type calcium current, ICaL) and KCNH2 (rapid delayed rectifier K+ current, IKr), which was verified in mRNA extracted from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). In silico modeling, validated with functional measurements in hiPSC-CM, indicates that the co-expression of CACNA1C and KCNH2 limits the variability in action potential duration and reduces susceptibility to early afterdepolarizations, a surrogate marker for pro-arrhythmia.Impact StatementCoexpressed levels of potassium and calcium ion channel genes in the heart encode more robust cardiac electrophysiology and provide insights into genetic basis of arrhythmic risk

scholarly journals Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression

2021 ◽  
Vol 14 (7) ◽  
pp. 597
Author(s):  
Noha E. Farag ◽  
Mohamed K. El-Kherbetawy ◽  
Hussein M. Ismail ◽  
Ahmed M. Abdelrady ◽  
Eman A. Toraih ◽  
...  
Keyword(s):  
Cardiac Electrophysiology ◽  
Elevated Serum ◽  
Macrolide Antibiotics ◽  
Albino Rats ◽  
Ecg Changes ◽  
Increased Risk ◽  
Channel Expression ◽  
Oral Doses ◽  
Electrocardiogram Ecg ◽  
The Impact

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with erythromycin in healthy rats. Although rats with MI did not show further elevations in fibrosis score on treatment with macrolides, they produced significant fibrosis in healthy rats. Downregulation of cardiac Nav1.5 transcript was observed following macrolides treatment in both groups (healthy rats and rats with MI). In conclusion, the current findings suggested the potential cardiotoxic effects of chronic doses of macrolide antibiotics in rats with MI as manifested by abnormal ECG changes and pathological findings in addition to downregulation of Nav1.5 channels. Furthermore, in the current dose ranges, azithromycin produced the least toxicity compared to clarithromycin and erythromycin.

Electrical remodeling in a transgenic mouse model of α1B-adrenergic receptor overexpression

2009 ◽  
Vol 296 (3) ◽  
pp. H704-H718 ◽  
Author(s):  
Katy Rivard ◽  
Véronique Trépanier-Boulay ◽  
Hansjorg Rindt ◽  
Céline Fiset
Keyword(s):  
Heart Failure ◽  
Ventricular Arrhythmias ◽  
Transgenic Animals ◽  
Delayed Rectifier ◽  
Electrical Remodeling ◽  
Adrenergic Stimulation ◽  
Channel Expression ◽  
End Stage ◽  
Electrocardiogram Ecg

Cardiac-specific overexpression of wild-type α1B-adrenergic receptors (α1B-AR) in mice predisposes to dilated cardiomyopathy and sudden death. Although α-adrenergic stimulation is thought to contribute to induction of arrhythmias in heart failure, the electrophysiological consequences of chronic α1-adrenergic activation have not been clearly defined. Thus we characterized ventricular repolarization and monitored incidence of spontaneous arrhythmias in end-stage heart failure α1B-AR mice (9–12 mo) and younger α1B-AR mice (2–3 mo) that do not present signs of heart failure. Compared with aged-matched controls, the corrected QT interval was 34% longer in the 9- to 12-mo α1B-AR mice, and the action potential durations were also significantly prolonged in these mice. These changes were associated with a decrease in the density of the outward K+ currents, Ca2+-independent transient, ultrarapid delayed rectifier, and steady state (at +30 mV, reduction of 68, 64, and 41%, respectively), and underlying K+ channel expression. Electrocardiogram (ECG) recordings revealed that older α1B-AR mice exhibited spontaneous ventricular arrhythmias. The alterations in repolarization can contribute to these rhythm abnormalities and are likely caused by chronic α1B-AR activity. Additional data obtained in 2- to 3-mo α1B-AR mice clearly showed that electrical remodeling was already observed in younger transgenic animals. However, it appeared to be slightly less pronounced than in older mice. These results suggest that there are two waves of remodeling: one due to chronic α1B-AR activity, and a second due to heart failure. Taken together, these data provide strong evidence for a pathological role of chronic α1B-AR activity in the development of repolarization defects and ventricular arrhythmias.

scholarly journals Automated Framework for the Inclusion of a His–Purkinje System in Cardiac Digital Twins of Ventricular Electrophysiology

2021 ◽  
Author(s):  
Karli Gillette ◽  
Matthias A. F. Gsell ◽  
Julien Bouyssier ◽  
Anton J. Prassl ◽  
Aurel Neic ◽  
...  
Keyword(s):  
Cardiac Electrophysiology ◽  
Ventricular Myocardium ◽  
Activation Patterns ◽  
Purkinje System ◽  
Digital Twins ◽  
Emergent Features ◽  
Ventricular Activation ◽  
Endocardial Layer ◽  
Right Ventricular Apical Pacing ◽  
Electrocardiogram Ecg

AbstractPersonalized models of cardiac electrophysiology (EP) that match clinical observation with high fidelity, referred to as cardiac digital twins (CDTs), show promise as a tool for tailoring cardiac precision therapies. Building CDTs of cardiac EP relies on the ability of models to replicate the ventricular activation sequence under a broad range of conditions. Of pivotal importance is the His–Purkinje system (HPS) within the ventricles. Workflows for the generation and incorporation of HPS models are needed for use in cardiac digital twinning pipelines that aim to minimize the misfit between model predictions and clinical data such as the 12 lead electrocardiogram (ECG). We thus develop an automated two stage approach for HPS personalization. A fascicular-based model is first introduced that modulates the endocardial Purkinje network. Only emergent features of sites of earliest activation within the ventricular myocardium and a fast-conducting sub-endocardial layer are accounted for. It is then replaced by a topologically realistic Purkinje-based representation of the HPS. Feasibility of the approach is demonstrated. Equivalence between both HPS model representations is investigated by comparing activation patterns and 12 lead ECGs under both sinus rhythm and right-ventricular apical pacing. Predominant ECG morphology is preserved by both HPS models under sinus conditions, but elucidates differences during pacing.

scholarly journals Cardiac Transmembrane Ion Channels and Action Potentials: Cellular Physiology and Arrhythmogenic Behavior

2020 ◽  
Author(s):  
András Varró ◽  
Jakub Tomek ◽  
Norbert Nagy ◽  
Laszlo Virag ◽  
Elisa Passini ◽  
...  
Keyword(s):  
Ion Channel ◽  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Current Knowledge ◽  
Animal Experiments ◽  
Cardiac Cells ◽  
Cellular Mechanisms ◽  
Electrophysiological Properties ◽  
Channel Expression ◽  
Ionic Mechanisms

Cardiac arrhythmias are among the leading causes of mortality. They often arise from alterations in the electrophysiological properties of cardiac cells, and their underlying ionic mechanisms. It is therefore critical to further unravel the patho-physiology of the ionic basis of human cardiac electrophysiology in health and disease. In the first part of this review, current knowledge on the differences in ion channel expression and properties of the ionic processes that determine the morphology and properties of cardiac action potentials and calcium dynamics from cardiomyocytes in different regions of the heart are described. Then the cellular mechanisms promoting arrhythmias in congenital or acquired conditions of ion channel function (electrical remodelling) are discussed. The focus is human relevant findings obtained with clinical, experimental and computational studies, given that interspecies differences make the extrapolation from animal experiments to the human clinical settings difficult. Deepening the understanding of the diverse patholophysiology of human cellular electrophysiology will help developing novel and effective antiarrhythmic strategies for specific subpopulations and disease conditions.

Chronic heart rate reduction remodels ion channel transcripts in the mouse sinoatrial node but not in the ventricle

2006 ◽  
Vol 24 (1) ◽  
pp. 4-12 ◽  
Author(s):  
Anne-Laure Leoni ◽  
Céline Marionneau ◽  
Sophie Demolombe ◽  
Sabrina Le Bouter ◽  
Matteo E. Mangoni ◽  
...  
Keyword(s):  
Heart Rate ◽  
Ion Channel ◽  
Clustering Analysis ◽  
Connexin 43 ◽  
Sinoatrial Node ◽  
Rt Pcr ◽  
Cardiac Electrical Activity ◽  
Channel Expression ◽  
Freely Moving ◽  
Α Subunits

We investigated the effects of chronic and moderate heart rate (HR) reduction on ion channel expression in the mouse sinoatrial node (SAN) and ventricle. Ten-week-old male C57BL/6 mice were treated twice daily with either vehicle or ivabradine at 5 mg/kg given orally during 3 wk. The effects of HR reduction on cardiac electrical activity were investigated in anesthetized mice with serial ECGs and in freely moving mice with telemetric recordings. With the use of high-throughput real-time RT-PCR, the expression of 68 ion channel subunits was evaluated in the SAN and ventricle at the end of the treatment period. In conscious mice, ivabradine induced a mean 16% HR reduction over a 24-h period that was sustained over the 3-wk administration. Other ECG parameters were not modified. Two-way hierarchical clustering analysis of gene expression revealed a separation of ventricles from SANs but no discrimination between treated and untreated ventricles, indicating that HR reduction per se induced limited remodeling in this tissue. In contrast, SAN samples clustered in two groups depending on the treatment. In the SAN from ivabradine-treated mice, the expression of nine ion channel subunits, including Navβ1 (−25%), Cav3.1 (−29%), Kir6.1 (−28%), Kvβ2 (−41%), and Kvβ3 (−30%), was significantly decreased. Eight genes were significantly upregulated, including K+ channel α-subunits (Kv1.1, +30%; Kir2.1, +29%; Kir3.1, +41%), hyperpolarization-activated cation channels (HCN2, +24%; HCN4, +52%), and connexin 43 (+26%). We conclude that reducing HR induces a complex remodeling of ion channel expression in the SAN but has little impact on ion channel transcripts in the ventricle.

scholarly journals Dissociation between Cervical Mucus and Urinary Hormones during the Postpartum Return of Fertility in Breastfeeding Women

2018 ◽  
Vol 85 (4) ◽  
pp. 399-411
Author(s):  
Thomas Bouchard ◽  
Len Blackwell ◽  
Simon Brown ◽  
Richard Fehring ◽  
Suzanne Parenteau-Carreau
Keyword(s):  
Postpartum Period ◽  
Cervical Mucus ◽  
Urine Samples ◽  
Postpartum Women ◽  
Hormonal Changes ◽  
Urinary Hormones

Identifying the return of fertility with cervical mucus observations is challenging during the postpartum period. Use of urinary measurements of estrogen and progesterone can assist in understanding the return to fertility during this period. The purposes of this study were to describe the postpartum return of fertility by an analysis of total estrogen (TE) and pregnanediol glucuronide (PDG) profiles and to correlate these profiles with cervical mucus observations. Twenty-six participants collected urine samples during the postpartum period and recorded mucus scores. TE and PDG hormones were analyzed and compared with mucus scores. During amenorrhea, mucus reflected TE changes in only 35 percent of women; after amenorrhea, typical mucus patterns were seen in 33 percent of cycles. We concluded that postpartum mucus and hormone profiles are significantly dissociated but that monitoring urinary hormones may assist in identifying the return of fertility. We also identified different hormonal patterns in the return to fertility. The postpartum period is a challenging time for identifying the return of fertility. The purposes of this study were to describe the hormonal patterns during the return of fertility and to correlate these patterns with cervical mucus observations. Twenty-six postpartum women collected urine samples and recorded mucus scores. Urinary estrogen and progesterone hormones were analyzed and compared with mucus scores. Before the return of menses, mucus reflected hormonal changes in only 35 percent women and after first menses in 33 percent of cycles. We found that hormone profiles do not correlate well with mucus observations during the postpartum return of fertility.

scholarly journals Researches Regarding the Values of Some Electrocardiogram’S Components in Cats

2018 ◽  
Vol 75 (1) ◽  
pp. 139
Author(s):  
Cristian BROJBĂ
Keyword(s):  
Electrical Activity ◽  
Reference Values ◽  
Biological Material ◽  
Research Work ◽  
Cardiac Diseases ◽  
Cardiac Electrical Activity ◽  
Main Target ◽  
Main Components ◽  
Electrocardiogram Ecg ◽  
Ecg Interpretation

The electrocardiogram (ECG or EKG) represents the graphical recording of the cardiac electrical activity (Ghiţă et al., 2005) and it is useful in the diagnosis in some cardiac diseases (such as rhythm disorders) (Cotor and Ghiţă, 2014) or frequency disorders (Ghiţă et al., 2007).The main target of this research work was to determine the values of the main components of the ECG and the cardiac frequency. The biological material was represented by 12 healthy cats of different breeds. The values obtained in this research work can be used as reference values in ECG interpretation in cats.

scholarly journals Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration

2000 ◽  
Vol 278 (2) ◽  
pp. C303-C314 ◽  
Author(s):  
Jian-Ying Wang ◽  
Jian Wang ◽  
Vera A. Golovina ◽  
Li Li ◽  
Oleksandr Platoshyn ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Driving Force ◽  
Intestinal Epithelial Cell ◽  
Delayed Rectifier ◽  
Intestinal Epithelial ◽  
Voltage Gated ◽  
Epithelial Cell Migration ◽  
Channel Expression ◽  
Exogenous Spermidine

Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K+ channels (Kv) controls membrane potential ( E m) that regulates cytoplasmic free Ca2+ concentration ([Ca2+]cyt) by governing the driving force for Ca2+ influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K+ channel gene expression, E m, and [Ca2+]cyt in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, α-difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca2+ channels, the depolarized E m in DFMO-treated cells decreased [Ca2+]cyt as a result of reduced driving force for Ca2+ influx through capacitative Ca2+ entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E m, and [Ca2+]cyt but also restored cell migration to normal. Removal of extracellular Ca2+ or blockade of Kv channels (by 4-aminopyridine, 1–5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca2+]cyt by increasing the driving force (the electrochemical gradient) for Ca2+ influx and thus stimulates cell migration.

scholarly journals Computational approaches to understand cardiac electrophysiology and arrhythmias

2012 ◽  
Vol 303 (7) ◽  
pp. H766-H783 ◽  
Author(s):  
Byron N. Roberts ◽  
Pei-Chi Yang ◽  
Steven B. Behrens ◽  
Jonathan D. Moreno ◽  
Colleen E. Clancy
Keyword(s):  
Ion Channels ◽  
Electrical Activity ◽  
Cardiac Electrophysiology ◽  
Cardiac Activity ◽  
Computational Approaches ◽  
Cardiac Electrical Activity ◽  
Whole Heart ◽  
Arrhythmia Therapy ◽  
Emergent Behaviors ◽  
The Brain

Cardiac rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. These impulses spread throughout the cardiac muscle to manifest as electrical waves in the whole heart. Regularity of electrical waves is critically important since they signal the heart muscle to contract, driving the primary function of the heart to act as a pump and deliver blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. For more than 50 years, mathematically based models of cardiac electrical activity have been used to improve understanding of basic mechanisms of normal and abnormal cardiac electrical function. Computer-based modeling approaches to understand cardiac activity are uniquely helpful because they allow for distillation of complex emergent behaviors into the key contributing components underlying them. Here we review the latest advances and novel concepts in the field as they relate to understanding the complex interplay between electrical, mechanical, structural, and genetic mechanisms during arrhythmia development at the level of ion channels, cells, and tissues. We also discuss the latest computational approaches to guiding arrhythmia therapy.

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