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Cells Jun 2024This manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (K) channels in the pathogenesis of atrial fibrillation (AF), a common... (Review)
Review
This manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (K) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of K channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of K activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.4 and K3.1, significantly influence the electrophysiological remodeling associated with AF. Furthermore, this manuscript identifies the crucial role of the K-mediated current, , in sustaining arrhythmia through facilitating shorter re-entry circuits and stabilizing the re-entrant circuits, particularly in response to vagal nerve stimulation. Experimental findings from animal models, which could not induce AF in the absence of muscarinic activation, highlight the dependency of AF induction on K channel activity. This is complemented by discussions on therapeutic interventions, where K channel blockers have shown promise in AF management. Additionally, this study discusses the broader implications of K channel behavior, including its ubiquitous presence across different cardiac regions and species, contributing to a comprehensive understanding of AF dynamics. The implications of these findings are profound, suggesting that targeting K channels might offer new therapeutic avenues for AF treatment, particularly in cases resistant to conventional approaches. By integrating genetic, cellular, and pharmacological perspectives, this manuscript offers a holistic view of the potential mechanisms and therapeutic targets in AF, making a significant contribution to the field of cardiac arrhythmia research.
Topics: Atrial Fibrillation; Humans; Animals; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Action Potentials; Acetylcholine
PubMed: 38920645
DOI: 10.3390/cells13121014 -
Entropy (Basel, Switzerland) May 2024In the realm of cardiac research, the control of spiral waves and turbulent states has been a persistent focus for scholars. Among various avenues of investigation, the...
In the realm of cardiac research, the control of spiral waves and turbulent states has been a persistent focus for scholars. Among various avenues of investigation, the modulation of ion currents represents a crucial direction. It has been proved that the methods involving combined control of currents are superior to singular approaches. While previous studies have proposed some combination strategies, further reinforcement and supplementation are required, particularly in the context of controlling arrhythmias through the combined regulation of two potassium ion currents. This study employs the Luo-Rudy phase I cardiac model, modulating the maximum conductance of the time-dependent potassium current and the time-independent potassium current, to investigate the effects of this combined modulation on spiral waves and turbulent states. Numerical simulation results indicate that, compared to modulating a single current, combining reductions in the conductance of two potassium ion currents can rapidly control spiral waves and turbulent states in a short duration. This implies that employing blockers for both potassium ion currents concurrently represents a more efficient control strategy. The control outcomes of this study represent a novel and effective combination for antiarrhythmic interventions, offering potential avenues for new antiarrhythmic drug targets.
PubMed: 38920457
DOI: 10.3390/e26060446 -
Archive of Clinical Cases 2024Atrial fibrillation, the most common cardiac arrhythmia in the Western world, confers a 5-fold increase in stroke, mainly due to thrombus formation in the left atrial...
Atrial fibrillation, the most common cardiac arrhythmia in the Western world, confers a 5-fold increase in stroke, mainly due to thrombus formation in the left atrial appendage. Early rhythm control is often beneficial in reducing adverse cardiovascular events in higher-risk populations. Here, we present a patient who was found to have a 1 cm stalk-like lesion in the left atrial appendage on transesophageal echocardiogram prior to electrical cardioversion. Using multiple cardiac imaging modalities, including cardiac magnetic resonance imaging and computed tomography, the mass was eventually determined to be a chronic resolving thrombus.
PubMed: 38919848
DOI: 10.22551/2024.43.1102.10285 -
Archive of Clinical Cases 2024As the number of pacemaker insertions increases to manage numerous cardiac arrhythmias, the number of complications is also increasing as a result. More common...
As the number of pacemaker insertions increases to manage numerous cardiac arrhythmias, the number of complications is also increasing as a result. More common complications such as infection and lead displacement are routinely discussed with patients before they undergo the procedure. However rare complications such as superior vena cava syndrome are not discussed during the consenting period. But they do occur, as seen in this case of a 69-year-old male. This fit and active man had a right-sided dual-chamber pacemaker inserted due to sinus node disease and presented 5 years later with symptoms suggestive of superior vena cava obstruction (SVCO). Despite anticoagulation and before surgical intervention could be performed, the patient developed a right-sided chylothorax which was drained. An autologous pericardial patch repair of the SVC and a thrombectomy of SVC clots was subsequently performed. This was only partially successful and the SVCO recurred. A low fatty chain diet was initiated to manage the chylothorax, which remains stable. This rare complication has left the patient with a small pleural effusion and chronic pleural thickening. They can still exercise with mild breathlessness. The management of such a complication, which requires the input of many specialists, is challenging and often does not completely resolve all symptoms. For this reason, superior vena cava obstruction should be considered as a risk during the consenting procedure for a pacemaker insertion.
PubMed: 38919846
DOI: 10.22551/2024.43.1102.10288 -
Vascular Health and Risk Management 2024Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people... (Review)
Review
Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer's disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF.
Topics: Humans; Metformin; Atrial Fibrillation; Drug Repositioning; Hypoglycemic Agents; Animals; COVID-19; Anti-Arrhythmia Agents; Treatment Outcome; Diabetes Mellitus, Type 2
PubMed: 38919471
DOI: 10.2147/VHRM.S391808 -
Journal of Anaesthesiology, Clinical... 2024Cervical sympathetic or stellate ganglion blocks (SGBs) have been commonly used in the treatment of painful conditions like complex regional pain syndrome (CRPS).... (Review)
Review
Cervical sympathetic or stellate ganglion blocks (SGBs) have been commonly used in the treatment of painful conditions like complex regional pain syndrome (CRPS). However, there is literature to suggest its utility in managing non-painful conditions as well. The focus of this literature review is to provide an overview of indications for SGB for painful and non-painful conditions. We identified published journal articles in the past 25 years from Embase and PubMed databases with the keywords "cervical sympathetic block, stellate ganglion blocks, cervical sympathetic chain, and cervical sympathetic trunk". A total of 1556 articles were obtained from a literature search among which 311 articles were reviewed. Among painful conditions, there is a lack of evidence in favor of or against the use of SGB for CRPS despite its common use. SGB can provide postoperative analgesia in selective surgeries and can be effective in temporary pain control of refractory angina and the acute phase of herpes zoster infection. Among non-painful conditions, SGB may have beneficial effects on the management of post-traumatic stress disorder (PTSD), refractory ventricular arrhythmias, hot flashes in postmenopausal women, and breast cancer-related lymphedema. Additionally, there have been various case reports illustrating the benefits of SGB in the management of cerebral vasospasm, upper limb erythromelalgia, thalamic and central post-stroke pain, palmar hyperhidrosis, orofacial pain, etc. In our review of literature, we found that SGB can be useful in the management of various non-painful conditions beyond the well-known treatment for CRPS, although further studies are required to prove its efficacy.
PubMed: 38919437
DOI: 10.4103/joacp.joacp_304_22 -
Frontiers in Pharmacology 2024Ion channels are critical drug targets for a range of pathologies, such as epilepsy, pain, itch, autoimmunity, and cardiac arrhythmias. To develop effective and safe...
Ion channels are critical drug targets for a range of pathologies, such as epilepsy, pain, itch, autoimmunity, and cardiac arrhythmias. To develop effective and safe therapeutics, it is necessary to design small molecules with high potency and selectivity for specific ion channel subtypes. There has been increasing implementation of structure-guided drug design for the development of small molecules targeting ion channels. We evaluated the performance of two RosettaLigand docking methods, RosettaLigand and GALigandDock, on the structures of known ligand-cation channel complexes. Ligands were docked to voltage-gated sodium (Na), voltage-gated calcium (Ca), and transient receptor potential vanilloid (TRPV) channel families. For each test case, RosettaLigand and GALigandDock methods frequently sampled a ligand-binding pose within a root mean square deviation (RMSD) of 1-2 Å relative to the experimental ligand coordinates. However, RosettaLigand and GALigandDock scoring functions cannot consistently identify experimental ligand coordinates as top-scoring models. Our study reveals that the proper scoring criteria for RosettaLigand and GALigandDock modeling of ligand-ion channel complexes should be assessed on a case-by-case basis using sufficient ligand and receptor interface sampling, knowledge about state-specific interactions of the ion channel, and inherent receptor site flexibility that could influence ligand binding.
PubMed: 38919257
DOI: 10.3389/fphar.2024.1411428 -
Cureus May 2024Disturbances in potassium levels can induce ventricular arrhythmias and heighten mortality in patients with ST-elevation myocardial infarction (STEMI). This study...
INTRODUCTION
Disturbances in potassium levels can induce ventricular arrhythmias and heighten mortality in patients with ST-elevation myocardial infarction (STEMI). This study evaluates the influence of sK levels on seven-day mortality and incidence of ventricular arrhythmias in STEMI patients to further improve clinical guidelines and outcomes.
METHODS
This retrospective, propensity-matched study analyzed approximately 250,000 acute STEMI patients from 55 major academic medical centers/healthcare organizations (HCOs) in the US Collaborative Network of the TriNetX database. The sK levels recorded on the day of STEMI diagnosis were categorized into four cohorts: sK ≤ 3.4 (hypokalemia), 3.5 ≤ sK ≤ 4.5 (normal-control), 4.6 ≤ sK ≤ 5.0 (high-normal), and sK ≥ 5.1 (hyperkalemia). Patient cohorts were propensity-matched using linear and logistic regression for demographics. Outcomes of seven-day mortality, ventricular tachycardia (VT), and ventricular fibrillation (VF) were compared between these cohorts and the control group.
RESULTS
The analysis showed hypokalemia was linked to significantly higher seven-day mortality (7.2% vs. 4.3%; RR 1.69; p<0.001), and increased rates of VT and VF. Similarly, hyperkalemia was associated with elevated mortality (12.7% vs. 4.6%; RR 2.76; p<0.001), VT, and VF rates. High-normal sK levels showed increased mortality (7.4% vs. 4.7%; RR 1.58; p<0.001), but unchanged VT or VF rates compared to the normal sK group.
CONCLUSION
This comprehensive study highlights the correlation of sK levels with death in STEMI patients, revealing a nearly doubled risk of mortality with hypokalemia and almost triples with hyperkalemia. More notably, the mortality for STEMIs is higher for high-normal vs normal sK values. Additionally, hypokalemia and hyperkalemia were found to significantly elevate VT and VF risks.
PubMed: 38919213
DOI: 10.7759/cureus.61126 -
BMC Nursing Jun 2024The accurate diagnosis and effective management of arrhythmias are crucial, with nurses playing a key role in the early detection and treatment, significantly impacting...
BACKGROUND
The accurate diagnosis and effective management of arrhythmias are crucial, with nurses playing a key role in the early detection and treatment, significantly impacting patient outcomes. Improving education on arrhythmias among nurses, especially in critical care and perioperative settings, can enhance patient safety and the quality of care.
METHODS
A total of 116 trainee nurses were randomly divided into two groups: one utilizing the conceive-design-implement-operate (CDIO) model and the other employing a traditional lecture-based learning (LBL) method, to undergo arrhythmia training. The studyassessed the effects of the two teaching methods and investigated the students' attitudes toward these educational practices, with all participants completing pre- and post-course tests.
RESULTS
The CDIO model significantly enhances nursing students' arrhythmia proficiency, yielding higher test scores and sustained improvement after 24-week compared to the traditional LBL method, alongside markedly better self-learning enthusiasm, understanding, satisfaction with the teaching approach and effectiveness, and interest in learning arrhythmia. The CDIO model in nursing arrhythmia courses boosts theoretical knowledge and application, showing potential in clinical skill enhancement.
CONCLUSIONS
Our study introduces the CDIO model in nursing arrhythmia courses, with improvement in knowledge and skills, and promise for broader application.
PubMed: 38918825
DOI: 10.1186/s12912-024-02118-1 -
BMC Cardiovascular Disorders Jun 2024Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease (CHD) worldwide. It accounts for 7% of CHD cases in Uganda and leads to fatal...
BACKGROUND
Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease (CHD) worldwide. It accounts for 7% of CHD cases in Uganda and leads to fatal outcomes in the long term without surgery. Surgery is often delayed in developing countries like Uganda due to limited resources.
OBJECTIVE
This study aimed to determine the early surgical outcomes of patients with TOF who underwent primary intracardiac repair at the Uganda Heart Institute (UHI) and to identify factors associated.
METHODOLOGY
This retrospective chart review evaluated outcomes of primary TOF repair patients at UHI from February 2012 to October 2022. Patient outcomes were assessed from surgery until 30 days post-operation.
RESULTS
Out of the 104 patients who underwent primary TOF repair at UHI, records of 88 patients (84.6%) were available for review. Males accounted for 48.9% (n = 43). The median age at the time of operation was 4 years (with an interquartile range of 2.5-8.0 years), ranging from 9 months to 16 years. Genetic syndromes were present in 5/88 (5.7%). These included 2 patients with trisomy 21, 2 with Noonan's, and 1 with 22q11.2 deletion syndrome. Early postoperative outcomes for patients included: residual ventricular septal defects in 35/88 (39.8%), right ventricular dysfunction in 33/88 (37.5%), residual pulmonary regurgitation in 27/88 (30.7%), residual right ventricular outflow tract obstruction in 27/88 (30.0%), pleural effusion in 24/88 (27.3%), arrhythmias in 24/88(27.3%), post-operative infections in 23/88(26.1%) and left ventricular systolic dysfunction in 9/88 (10.2%). Out of the children who underwent surgery after one year of age, 8% (7 children) died within the first 30 days. There was a correlation between mortality and post-operative ventilation time, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, preoperative oxygen saturations, RV and LV dysfunction and the operating team.
CONCLUSION
The most frequent outcomes after surgery were residual ventricular septal defects and right ventricular failure. In our study, the 30-day mortality rate following TOF repair was 8%. Deceased patients had lower pre-operative oxygen levels, longer CPB and cross-clamp times, longer post-operative ventilation, RV/LV dysfunction, and were more likely operated by the local team.
Topics: Humans; Tetralogy of Fallot; Male; Retrospective Studies; Female; Uganda; Child, Preschool; Child; Adolescent; Infant; Cardiac Surgical Procedures; Treatment Outcome; Time Factors; Risk Factors; Postoperative Complications; Risk Assessment
PubMed: 38918721
DOI: 10.1186/s12872-024-03991-z