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https://www.readbyqxmd.com/read/28623610/a-singular-role-of-ik1-promoting-the-development-of-cardiac-automaticity-during-cardiomyocyte-differentiation-by-ik1-induced-activation-of-pacemaker-current
#1
Yu Sun, Valeriy Timofeyev, Adrienne Dennis, Emre Bektik, Xiaoping Wan, Kenneth R Laurita, Isabelle Deschênes, Ronald A Li, Ji-Dong Fu
The inward rectifier potassium current (IK1) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that IK1 could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (If) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of IK1 to activate If and thereby promote automaticity has not been explored. In this study, we combined mathematical and experimental assays and found that only IK1 and If, at a proper-ratio of densities, were sufficient to generate rhythmic MP-oscillations even in unexcitable cells (i...
June 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28454527/effect-of-ivabradine-on-cardiovascular-outcomes-in-patients-with-stable-angina-meta-analysis-of-randomized-clinical-trials
#2
Hayelom Gebrekirstos Mengesha, Berhe Weldearegawi, Pammala Petrucka, Tadese Bekele, Mala George Otieno, Abraha Hailu
BACKGROUND: Although there are established drugs for treatment of cardiovascular diseases, due to adverse effects these drugs may not be clinically applicable to all patients. Recent trends have seen the emergence of drugs which act on funny current channels to induce selective heart rate reduction. Ivabradine is one such drug developed for coronary artery disease and heart failure. There is inconsistent evidence about the effect of this selective inhibitor in reduction of cardiovascular related mortality and morbidity...
April 28, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28422759/ryr2r420q-catecholaminergic-polymorphic-ventricular-tachycardia-mutation-induces-bradycardia-by-disturbing-the-coupled-clock-pacemaker-mechanism
#3
Yue Yi Wang, Pietro Mesirca, Elena Marqués-Sulé, Alexandra Zahradnikova, Olivier Villejoubert, Pilar D'Ocon, Cristina Ruiz, Diana Domingo, Esther Zorio, Matteo E Mangoni, Jean-Pierre Benitah, Ana María Gómez
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests syncope or sudden death in children and young adults under stress conditions. CPVT patients often present bradycardia and sino-atrial node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN function in two CPVT families and in a novel knock-in (KI) mouse model carrying the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate. Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was slower in KI mouse SAN preparations than in WT, without any significant alteration in the "funny" current (If )...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28371247/ivabradine-current-and-future-treatment-of-heart-failure
#4
REVIEW
Lene Thorup, Ulf Simonsen, Daniela Grimm, Elise R Hedegaard
In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28352365/heart-failure-modulates-electropharmacological-characteristics-of-sinoatrial-nodes
#5
Shih-Lin Chang, Hui-Lun Chuang, Yao-Chang Chen, Yu-Hsun Kao, Yung-Kuo Lin, Yung-Hsin Yeh, Shih-Ann Chen, Yi-Jen Chen
The impact of heart failure (HF) on sinoatrial node (SAN) channel regulation and electropharmacological responses has remained elusive. The present study aimed to investigate the effects of HF on the electrical activity of SANs with and without pharmacological interventions. Action potentials (APs) were recorded in isolated SANs from normal rabbits (control) and those with HF (rapid ventricular pacing for 4 weeks) prior to and after administration of a funny current blocker (ivabradine; 0.1, 0.3, 3 or 10 µM), a calmodulin kinase II inhibitor (KN-93; 0...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28256323/ivabradine-in-acute-coronary-syndromes-protection-beyond-heart-rate-lowering
#6
Giampaolo Niccoli, Josip Anđelo Borovac, Vincenzo Vetrugno, Paolo G Camici, Filippo Crea
Ivabradine is a heart rate reducing agent that exhibits anti-ischemic effects through the inhibition of funny electrical current in the sinus node resulting in heart rate reduction, thus enabling longer diastolic perfusion time, and reduced myocardial oxygen consumption without detrimental changes in arterial blood pressure, coronary vasomotion, and ventricular contractility. The current guideline-based clinical use of Ivabradine is reserved for patients with stable angina pectoris who cannot tolerate or whose symptoms are inadequately controlled with beta blockers...
June 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28217366/crizotinib-inhibits-hyperpolarization-activated-cyclic-nucleotide-gated-channel-4-activity
#7
Zhushan Zhang, Tai-Qin Huang, Igor Nepliouev, Hengtao Zhang, Adam S Barnett, Paul B Rosenberg, Sai-Hong I Ou, Jonathan A Stiber
BACKGROUND: Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We investigated whether crizotinib could influence heart rate (HR) through direct cardiac effects. METHODS: The direct effect of crizotinib on HR was studied using ECG analysis of Langendorff-perfused mouse hearts. The whole-cell patch clamp technique was used to measure the effects of crizotinib on the hyperpolarization-activated funny current, If, in mouse sinoatrial node cells (SANCs) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) activity in HEK-293 cells stably expressing human HCN4...
2017: Cardio-Oncology
https://www.readbyqxmd.com/read/28185290/computational-analysis-of-the-human-sinus-node-action-potential-model-development-and-effects-of-mutations
#8
Alan Fabbri, Matteo Fantini, Ronald Wilders, Stefano Severi
KEY POINTS: We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi-DiFrancesco model of rabbit SAN cells. Our model is based on electrophysiological data from isolated human SAN pacemaker cells and closely matches the action potentials and calcium transient that were recorded experimentally. Simulated ion channelopathies explain the clinically observed changes in heart rate in corresponding mutation carriers, providing an independent qualitative validation of the model...
April 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28057842/cyclic-amp-reverses-the-effects-of-aging-on-pacemaker-activity-and-if-in-sinoatrial-node-myocytes
#9
Emily J Sharpe, Eric D Larson, Catherine Proenza
Aerobic capacity decreases with age, in part because of an age-dependent decline in maximum heart rate (mHR) and a reduction in the intrinsic pacemaker activity of the sinoatrial node of the heart. Isolated sinoatrial node myocytes (SAMs) from aged mice have slower spontaneous action potential (AP) firing rates and a hyperpolarizing shift in the voltage dependence of activation of the "funny current," If Cyclic AMP (cAMP) is a critical modulator of both AP firing rate and If in SAMs. Here, we test the ability of endogenous and exogenous cAMP to overcome age-dependent changes in acutely isolated murine SAMs...
February 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/27895488/advances-in-the-management-of-heart-failure-the-role-of-ivabradine
#10
REVIEW
Ursula Müller-Werdan, Georg Stöckl, Karl Werdan
A high resting heart rate (≥70-75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect...
2016: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/27803673/electrophysiological-mechanisms-of-brugada-syndrome-insights-from-pre-clinical-and-clinical-studies
#11
REVIEW
Gary Tse, Tong Liu, Ka H C Li, Victoria Laxton, Yin W F Chan, Wendy Keung, Ronald A Li, Bryan P Yan
Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the SCN5A, which encodes for the cardiac Na(+) channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na(+), K(+), Ca(2+), and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27784216/ivabradine-a-current-overview
#12
Kaushik Guha, Christopher J Allen, Adam Hartley, Rakesh Sharma
Ivabradine, acting on the funny channel (If) in the sino-atrial node, reduces myocardial oxygen demand without inducing hypotension. It was developed as a specific bradycardic agent in the 1980s, avoiding the adverse effects of more traditional antianginal agents (beta-blockers and calcium channel antagonists). This has seen significant interest in this first-in-class treatment, and is perceived as a promising drug in the management of ischaemic heart disease and heart failure. There has been much clinical research conducted exploring its role in these fields, to try to elucidate potential benefits and target patient group...
2016: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/27752846/ivabradine
#13
Michel Komajda
Ivabradine is a blocker of the funny current channels in the sinoatrial node cells. This results in pure heart rate reduction when elevated without direct effect on contractility or on the vessels. It was tested in a large outcome clinical trial in stable chronic heart failure (CHF) with low ejection fraction, in sinus rhythm, on a contemporary background therapy including betablockers (SHIFT: Systolic Heart Failure Treatment with the If inhibitor Trial).The primary composite endpoint (cardiovascular mortality or heart failure hospitalization) was reduced by 18% whereas the first occurrence of heart failure hospitalizations was reduced by 26%...
October 18, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27659287/emerging-role-of-ivabradine-for-rate-control-in-atrial-fibrillation
#14
REVIEW
Sarah L Turley, Kerry E Francis, Denise K Lowe, William D Cahoon
Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through If ('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment...
December 2016: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/27555825/-the-bitter-laughter-when-parody-is-a-moral-and-affective-priming-in-political-persuasion
#15
Francesca D'Errico, Isabella Poggi
Research on socially aware systems requires fine-grained knowledge of the mechanisms of persuasion in order to promote civic knowledge and aware political participation. Within humor studies, political parody is generally considered a simple pleasant weapon for political evaluation, currently explained by referring to the so called "just a joke effect" (Nabi et al., 2007). Indeed the funny side of parody can induce positive emotions, but it also includes a discrediting act that sometimes produces a "bitter laughter...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27547256/strategically-funny-romantic-motives-affect-humor-style-in-relationship-initiation
#16
Theresa E DiDonato, Brittany K Jakubiak
Not all humor is the same, yet little is known about the appeal of specific humor styles in romantic initiation. The current experimental study addresses this gap by investigating how romantic motives (short-term or long-term) affect individuals' anticipated use of, and response to, positive humor and negative humor. Heterosexual participants (n = 224) imagined the pursuit of either a desired short-term or long-term relationship, indicated the extent to which they would produce positive and negative humor, and reported how their own interest would change in response to the imaginary target's use of positive or negative humor...
August 2016: Europe's journal of psychology
https://www.readbyqxmd.com/read/27295092/prenatal-nicotine-exposure-results-in-the-inhibition-of-baroreflex-sensitivity-induced-by-intravenous-injection-angiotensin-ii-in-the-adult-male-offspring-rats
#17
Feng Yu, Yuexia Li, Jian Yang, Jin Qian, Xining Li, Chongbin Liu
Epidemiological studies show that maternal cigarette smoking is associated with an increased risk of cardiovascular diseases in postnatal life. Baroreflex sensitivity (BRS) is an important index for evaluating the homeostasis of the cardiovascular system. This experiment was designed to investigate the possible mechanism of prenatal nicotine on the adult male offspring's heart rate (HR) increase due to BRS. Pregnant rats received the 0.3 ml of saline or nicotine (1.5 mg kg(-1)) by subcutaneous injection from gestational days 3 to 21...
June 13, 2016: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/27136298/-jimmy-cap-before-you-tap-developing-condom-use-messages-for-african-american-women
#18
Kristina B Hood, Natalie J Shook, Faye Z Belgrave
This study examined which characteristics of persuasive communications are most effective in changing African American women's condom use attitudes. Focus groups were convened with 40 African American women (Mage = 25.54, SD = 4.67) to assess their opinions on current effective strategies used to promote condom use among their peers. Participants discussed effective characteristics of messaging campaigns (i.e., source, message type, channel) and how these could be used in future prevention messages. Findings revealed that making messages that are fun, catchy, and informative, delivered frequently through social media, TV, or radio by a peer or celebrity would be perceived as most effective in changing young African American women's attitudes...
May 2017: Journal of Sex Research
https://www.readbyqxmd.com/read/27073443/electric-pulse-current-stimulation-increases-electrophysiological-properties-of-if-current-reconstructed-in-mhcn4-transfected-canine-mesenchymal-stem-cells
#19
Yuanyuan Feng, Shouming Luo, Pan Yang, Zhiyuan Song
The 'funny' current, also known as the If current, play a crucial role in the spontaneous diastolic depolarization of sinoatrial node cells. The If current is primarily induced by the protein encoded by the hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) gene. The functional If channel can be reconstructed in canine mesenchymal stem cells (cMSCs) transfected with mouse HCN4 (mHCN4). Biomimetic studies have shown that electric pulse current stimulation (EPCS) can promote cardiogenesis in cMSCs...
April 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27059112/inappropriate-sinus-tachycardia-focus-on-ivabradine
#20
REVIEW
H S Abed, J R Fulcher, M J Kilborn, A C Keech
Inappropriate sinus tachycardia (IST) is an incompletely understood condition, characterised by an elevation in heart rate (HR) accompanied by wide ranging symptoms in the absence of an underlying physiological stimulus. The condition often takes a chronic course with significant adverse effects on quality of life. Currently, there is no effective treatment for IST. Beta-blockers, generally considered the cornerstone of treatment, are often ineffective and poorly tolerated. Ivabradine is a novel sinus node If 'funny current' inhibitor, which reduces the HR...
August 2016: Internal Medicine Journal
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