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Basic Research in Cardiology Mar 2022The role of long non-coding RNA (lncRNA) in endogenous cardiac regeneration remains largely elusive. The mammalian cardiomyocyte is capable of regeneration for a brief...
The role of long non-coding RNA (lncRNA) in endogenous cardiac regeneration remains largely elusive. The mammalian cardiomyocyte is capable of regeneration for a brief period after birth. This fact allows the exploration of the roles of critical lncRNAs in the regulation of cardiac regeneration. Through a cardiac regeneration model by apical resection (AR) of the left ventricle in neonatal mice, we identified an lncRNA named natriuretic peptide A antisense RNA 1 (NPPA-AS1), which negatively regulated cardiomyocyte proliferation. In neonates, NPPA-AS1 deletion did not affect heart development, but was sufficient to prolong the postnatal window of regeneration after AR. In adult mice, NPPA-AS1 deletion improved cardiac function and reduced infarct size after myocardial infarction (MI), associated with a significant improvement in cardiomyocyte proliferation. Further analysis showed that NPPA-AS1 interacted with DNA repair-related molecule splicing factor, proline- and glutamine-rich (SFPQ). A heteromer of SFPQ and non-POU domain-containing octamer-binding protein (NONO) was required for double-strand DNA break repair, but NPPA-AS1 was competitively bound with SFPQ due to the overlapped binding sites of SFPQ and NONO. NPPA-AS1 deletion promoted the binding of SFPQ-NONO heteromer, decreased DNA damage, and activated cardiomyocyte cell cycle re-entry. Together, loss of NPPA-AS1 promoted cardiomyocyte proliferation by stabilizing SFPQ-NONO heteromer-induced DNA repair and exerted a therapeutic effect against MI in adult mice. Consequently, NPPA-AS1 may be a novel target for stimulating cardiac regeneration to treat MI.
Topics: Animals; Atrial Natriuretic Factor; Cell Proliferation; DNA Repair; DNA-Binding Proteins; Mammals; Mice; Myocardial Infarction; Myocytes, Cardiac; Procainamide; RNA, Long Noncoding; RNA-Binding Proteins; Regeneration
PubMed: 35247074
DOI: 10.1007/s00395-022-00921-y -
World Journal of Cardiology Feb 2016Epigenetic modifications include DNA methylation, histone modifications, and microRNA. Gene alterations have been found to be associated with cardiovascular diseases,... (Review)
Review
Epigenetic modifications include DNA methylation, histone modifications, and microRNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of CpG islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression (e.g., hydralazine and procainamide) are currently under investigation. The anti-proliferative and anti-inflammatory properties of histone deacetylase inhibitors and their cardio-protective effects have been confirmed in preclinical studies. Furthermore, the regulation of the expression of microRNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense microRNAs could offer better therapeutic benefits in clinical practice. Here, we updated therapeutic properties, side effects, and feasibility of emerging epigenetic-based strategies in cardiovascular diseases by highlighting specific problematic issues that still affect the development of large scale novel therapeutic protocols.
PubMed: 26981216
DOI: 10.4330/wjc.v8.i2.211 -
Arthritis & Rheumatology (Hoboken, N.J.) Mar 2018Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The...
OBJECTIVE
Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The objective of this study was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation.
METHODS
Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy. The ability of these drugs to interfere with NET degradation by serum nuclei was assessed. Pathways of drug-induced NET formation were studied with pharmacologic inhibitors of reactive oxygen species (ROS), peptidylarginine deiminases (PADs), and muscarinic receptors, and by assessment of intracellular calcium levels by flow cytometry. To determine if NET protein cargo varies by drug stimulus and/or neutrophil source, proteomic analysis of NET lysates induced by specific medications was compared using neutrophils from healthy donors and from patients with autoimmune diseases.
RESULTS
Hydralazine and procainamide significantly induced NET formation while minocycline and clozapine did not. None of the medications significantly impaired NET degradation. NETosis induced by these drugs required NADPH oxidase and PAD4 activation. Procainamide triggered NETs via muscarinic receptor engagement on neutrophils, while hydralazine modulated calcium release from intracellular stores. Differences in protein cargo, particularly histone content, were observed in NETs induced by hydralazine and procainamide.
CONCLUSION
Medications commonly implicated in drug-induced autoimmunity trigger NET formation displaying distinct protein cargo, via common and specific pathways. NETosis may play a role in the pathogenesis of drug-induced autoimmunity.
Topics: Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antihypertensive Agents; Antipsychotic Agents; Autoimmunity; Clozapine; Extracellular Traps; Flow Cytometry; Humans; Hydralazine; Microscopy, Fluorescence; Minocycline; Neutrophils; Procainamide; Proteomics; Signal Transduction
PubMed: 29121457
DOI: 10.1002/art.40372 -
Journal of Community Hospital Internal... Jun 2020The Brugada pattern is identified on the EKG by a coved ST-segment elevation accompanied by a negative T wave in the early precordial leads in the absence of a cardiac... (Review)
Review
BACKGROUND
The Brugada pattern is identified on the EKG by a coved ST-segment elevation accompanied by a negative T wave in the early precordial leads in the absence of a cardiac structural abnormality. Brugada pattern and Brugada syndrome should be differentiated, as the latter is associated with an increased risk of sudden cardiac death.
METHODS
The literature was searched using multiple databases to identify all the articles on Brugada pattern. Data were screened and analyzed by independent authors.
RESULTS
Sixty articles, comprising 71 patients, were included in the study. The mean age of patients was 42.6 years, with a higher prevalence of Brugada pattern in men (83%) than women (17%). The most frequent findings associated with Brugada pattern was fever (83%). Other less common presentations included cough (21%), sore throat (10%), syncope (18%), abdominal pain (8%), and chest pain (7%). Comorbidities included pneumonia (30%), upper respiratory tract infections (14%) and smoking (14%). Among treatment modalities, 39% of patients had ICD placement performed, 44% received antibiotics, while 14% had supportive care. Adenosine was given to 3% of patients, while other antiarrhythmics like milrinone, amiodarone, sotalol, procainamide, flecainide, and nitroglycerin were given to 1% of patients. Most patients with Brugada syndrome had a satisfactory outcome, with only 4% mortality rate(WHAT ABOUT THE OTHER 11%?). Out of the 71 patients, 3% had persistent Brugada patterns, while 86% of patients recovered completely. There was no significant effect of ICD on mortality or Brugada pattern resolution (p 0.37).
CONCLUSION
Our study shows that fever is the main reason for unmasking the Brugada pattern in patients with this channelopathy. ICD placement in such patients is not recommended as it has no mortality benefits.
PubMed: 32850069
DOI: 10.1080/20009666.2020.1767278 -
Critical Care Nursing Quarterly 2015The development of cardiac arrhythmias in the intensive care unit is common and associated with poor prognoses and outcomes. Because of the complexity of patients... (Review)
Review
The development of cardiac arrhythmias in the intensive care unit is common and associated with poor prognoses and outcomes. Because of the complexity of patients admitted to the intensive care unit, the management of arrhythmias is often difficult and may require multiple therapeutic interventions. In order for clinicians to appropriately manage arrhythmias, a thorough understanding of all available therapies, including intravenous antiarrhythmic agents, is essential. Suitable antiarrhythmic agents for use in the critical care setting include amiodarone, lidocaine, and procainamide. While these agents can be effective in managing cardiac arrhythmias, they also possess significant disadvantages and require additional monitoring during use. Therapy with these agents is often complicated because of the presence of significant associated adverse effects, clinician unfamiliarity, variable dosing strategies, and the potential for drug-drug interactions. The purpose of this review is to discuss indications and strategies for safe and effective use of amiodarone, lidocaine, and procainamide.
Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drug Interactions; Humans; Infusions, Intravenous; Intensive Care Units; Lidocaine; Procainamide
PubMed: 26335213
DOI: 10.1097/CNQ.0000000000000082 -
Scandinavian Cardiovascular Journal :... Aug 2018In normal conditions, sudden heart rate acceleration provokes a rapid reduction in ventricular action potential duration (APD). The protracted APD rate adaptation favors... (Comparative Study)
Comparative Study
OBJECTIVES
In normal conditions, sudden heart rate acceleration provokes a rapid reduction in ventricular action potential duration (APD). The protracted APD rate adaptation favors early afterdepolarizations and precipitates arrhythmia. Nevertheless, it is uncertain as to whether the rate-dependent changes of ventricular repolarization can be adversely modified by arrhythmogenic drugs (quinidine and procainamide) and hypokalemia, in comparison to the agents with safe therapeutic profile, such as lidocaine.
DESIGN
The rate adaptation of QT interval and monophasic APD obtained from the left ventricular (LV) and the right ventricular (RV) epicardium was examined during rapid cardiac pacing applied in isolated, perfused guinea-pig heart preparations.
RESULTS
At baseline, an abrupt increase in cardiac activation rate was associated with a substantial reduction of the QT interval and ventricular APD in the first two cardiac cycles, which was followed by a gradual shortening of repolarization over subsequent pacing intervals. The time constants of the fast (τ) and slow (τ) components of the APD dynamics determined from a double exponential fit were longer in RV compared to LV chamber. Quinidine, procainamide, and hypokalemia prolonged ventricular repolarization and delayed the rate adaptation of the QT interval and APD in LV and RV, as evidenced by increased τ and τ values. In contrast, lidocaine had no effect on the dynamic changes of ventricular repolarization upon heart rate acceleration.
CONCLUSIONS
The rate adaptation of ventricular repolarization is delayed by arrhythmogenic interventions, such as quinidine, procainamide, and hypokalemia, but not changed by lidocaine, a clinically safe antiarrhythmic agent.
Topics: Action Potentials; Adaptation, Physiological; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Female; Guinea Pigs; Heart Rate; Heart Ventricles; Hypokalemia; Isolated Heart Preparation; Lidocaine; Procainamide; Quinidine; Time Factors; Ventricular Function, Left; Ventricular Function, Right
PubMed: 29798684
DOI: 10.1080/14017431.2018.1478123 -
Emergency Medicine Journal : EMJ Feb 2015We performed a systematic review of the literature to compare the efficacy of different drug therapies for the termination of stable, monomorphic ventricular tachycardia... (Review)
Review
OBJECTIVE
We performed a systematic review of the literature to compare the efficacy of different drug therapies for the termination of stable, monomorphic ventricular tachycardia (VT).
METHODS
We searched EMBASE, MEDLINE and Cochrane for trials from 1965 through July 2013 using a search strategy derived from the following clinical question in PICO format:
PATIENTS
Adults (≥18 years) with stable monomorphic VT;
INTERVENTION
Intravenous antidysrhythmic drug; Comparator: Intravenous lidocaine or amiodarone;
OUTCOME
Termination of VT. For all drug comparisons, we calculated relative risks (RR; 95% CI) and number needed to treat (NNT, 95% CI) between drugs. We also evaluated the methodological quality of the studies.
RESULTS
Our search yielded 219 articles by PubMed and 390 articles by EMBASE. 3 prospective studies (n=93 patients) and 2 retrospective studies (n=173 patients) met our inclusion and exclusion criteria. From the prospective studies, RR of VT termination of procainamide versus lidocaine was 3.7 (1.3-10.5); ajmaline versus lidocaine, RR=5.3 (1.4-20.5); and sotalol versus lidocaine, RR=3.9 (1.3-11.5). From the retrospective studies: procainamide versus lidocaine, RR=2.2 (1.2-4.0); and procainamide versus amiodarone RR=4.3 (0.8-23.6). All 5 reviewed studies had quality issues, including potential bias for randomisation and concealment.
CONCLUSIONS
Based on limited available evidence from small heterogeneous human studies, for the treatment of stable, monomorphic VT, procainamide, ajmaline and sotalol were all superior to lidocaine; amiodarone was not more effective than procainamide.
Topics: Administration, Intravenous; Anti-Arrhythmia Agents; Humans; Prospective Studies; Retrospective Studies; Tachycardia, Ventricular
PubMed: 24042252
DOI: 10.1136/emermed-2013-202973 -
Clinical Rheumatology Jun 2024The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is... (Review)
Review
The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.
Topics: Humans; Sulfides; Quinolines; Cyclopropanes; Acetates; Leukotriene Antagonists; Female; Churg-Strauss Syndrome; Male; Granulomatosis with Polyangiitis; Middle Aged; Adult
PubMed: 38720163
DOI: 10.1007/s10067-024-07000-8 -
Biomolecules May 2023A newly developed analytical strategy was applied to profile the total serum -glycome of 64 colorectal cancer (CRC) patients before and after surgical intervention. In...
A newly developed analytical strategy was applied to profile the total serum -glycome of 64 colorectal cancer (CRC) patients before and after surgical intervention. In this cohort, it was previously found that serum -glycome alterations in CRC were associated with patient survival. Here, fluorescent labeling of serum -glycans was applied using procainamide and followed by sialic acid derivatization specific for α2,6- and α2,3-linkage types via ethyl esterification and amidation, respectively. This strategy allowed efficient separation of specific positional isomers on reversed-phase liquid chromatography-fluorescence detection-mass spectrometry (RPLC-FD-MS) and complemented the previous glycomics data based on matrix-assisted laser desorption/ionization (MALDI)-MS that did not include such separations. The results from comparing pre-operative CRC to post-operative samples were in agreement with studies that identified a decrease in di-antennary structures with core fucosylation and an increase in sialylated tri- and tetra-antennary -glycans in CRC patient sera. Pre-operative abundances of -glycans showed good performance for the classification of adenocarcinoma and led to the revisit of the previous MALDI-MS dataset with regard to histological and clinical data. This strategy has the potential to monitor patient profiles before, during, and after clinical events such as treatment, therapy, or surgery and should also be further explored.
Topics: Humans; Glycosylation; Chromatography, Reverse-Phase; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Polysaccharides; Colorectal Neoplasms
PubMed: 37371476
DOI: 10.3390/biom13060896 -
Journal of Cardiovascular Pharmacology... May 2019Direct comparison of the effects of antiarrhythmic agents on myocardial performance may be useful in choosing between medications in critically ill patients. Studies... (Comparative Study)
Comparative Study
INTRODUCTION
Direct comparison of the effects of antiarrhythmic agents on myocardial performance may be useful in choosing between medications in critically ill patients. Studies directly comparing multiple antiarrhythmic medications are lacking. The use of an experimental heart preparation permits examination of myocardial performance under constant loading conditions.
METHODS
Hearts of Sprague Dawley rats (n = 35, 402-507 g) were explanted and cannulated in working heart model with fixed preload and afterload. Each heart was then exposed to a 3-hour infusion of procainamide (20 µg/kg/min), esmolol (100 or 200 µg/kg/min), amiodarone (10 or 20 mg/kg/d), sotalol (80 mg/m/d), or placebo infusions (n = 5 per dose). Cardiac output, contractility (dP/dT), diastolic performance (dP/dT), and heart rate were compared between groups over time by linear mixed modeling.
RESULTS
Compared with placebo, sotalol decreased contractility by an average of 24% ( P < .001) over the infusion period, as did amiodarone (low dose by 13%, P = .029; high dose by 14%, P = .013). Compared with placebo, mean cardiac output was significantly lower in animals treated with sotalol (by 22%, P = .016) and esmolol 200 μg/kg/min (by 23%, P = .012). Over time, amiodarone decreased cardiac output (20 mg/kg/d, β = -89 [-144, -33] μL/min decrease, P = .002) and also worsened diastolic function, decreasing dP/dT by ∼18% and 22% ( P = .032 and P = .011, low and high doses, respectively). Procainamide did not have a significant effect on any measures of systolic or diastolic performance.
CONCLUSIONS
In isolated hearts, amiodarone and sotalol depressed myocardial contractility, cardiac output, and diastolic function. However, procainamide did not negatively affect myocardial performance and represents a favorable agent in settings of therapeutic equivalence.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Cardiac Output; Dose-Response Relationship, Drug; Infusions, Intravenous; Isolated Heart Preparation; Myocardial Contraction; Procainamide; Rats, Sprague-Dawley; Risk Assessment; Sotalol; Ventricular Function, Left
PubMed: 30497293
DOI: 10.1177/1074248418810811