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International Journal of Molecular... Apr 2024Using a lipopolysaccharide model of acute lung injury, we previously showed that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper"...
Using a lipopolysaccharide model of acute lung injury, we previously showed that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. These studies provided a rationale for testing the effect of HJP272, an endothelin receptor antagonist (ERA), in hamster models of pulmonary fibrosis induced by intratracheal instillation of either bleomycin (BLM) or amiodarone (AM). To determine the temporal effects of blocking ET-1 activity, animals were given HJP272 either 1 h before initiation of lung injury or 24 h afterward. The results indicated that pretreatment with this agent caused significant reductions in various inflammatory parameters, whereas post-treatment was ineffective. This finding suggests that ERAs are only effective at a very early stage of pulmonary fibrosis and explains their lack of success in clinical trials involving patients with this disease. Nevertheless, ERAs could serve as prophylactic agents when combined with drugs that may induce pulmonary fibrosis. Furthermore, developing a biomarker for the initial changes in the lung extracellular matrix could increase the efficacy of ERAs and other therapeutic agents in preventing the progression of the disease. While no such biomarker currently exists, we propose the ratio of free to peptide-bound desmosine, a unique crosslink of elastin, as a potential candidate for detecting the earliest modifications in lung microarchitecture associated with pulmonary fibrosis.
Topics: Animals; Pulmonary Fibrosis; Endothelin Receptor Antagonists; Bleomycin; Cricetinae; Disease Models, Animal; Male; Lung; Humans; Endothelin-1
PubMed: 38673771
DOI: 10.3390/ijms25084184 -
Medicine Apr 2024To investigate whether postoperative administration of Shensong Yangxin capsules (SSYX) and dronedarone for atrial fibrillation (AF) can reduce the recurrence of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate whether postoperative administration of Shensong Yangxin capsules (SSYX) and dronedarone for atrial fibrillation (AF) can reduce the recurrence of paroxysmal AF after radiofrequency ablation, thus providing a more optimal choice of antiarrhythmic medication during the blank period.
METHODS
We included 120 patients with paroxysmal AF who underwent radiofrequency ablation at our hospital between July 2020 and July 2022. They underwent routine circumferential pulmonary vein ablation and, subsequently, left and right atrial pressure monitoring to assess sinoatrial node recovery time under burst 400/300 ms stimulation. Postoperatively, the patients were randomly divided into 2 groups (60 patients each). The control group was administered dronedarone orally for 3 months and the study group was treated with SSYX combined with dronedarone. This study aimed to compare differences in clinical efficacy of the treatment between the 2 groups.
RESULTS
The left and right atrial pressures in both groups were higher than those in the preoperative period (P < .05), with no statistically significant differences between the 2 groups (P > .05). Sinoatrial node recovery time under burst 400/300 ms stimulation showed no statistical difference between the 2 groups (P > .05). At 3 months and 1 year postoperatively, the AFEQT scale scores for both groups were lower than those before treatment (P < .05), with the study group scoring lower than the control group at 3 months (P < .05). However, no statistically significant difference was observed between the 2 groups at 1 year postoperatively (P > .05). At 3 months postoperatively, the sinus rhythm maintenance rate and heart rate were higher in the intervention group than in the control group (P < .05); however, these differences between the 2 groups were not statistically significant at 1 year postoperatively (P > .05).
CONCLUSION SUBSECTIONS
The combination of SSYX and dronedarone could effectively reduce the early recurrence of paroxysmal AF after radiofrequency ablation, increase heart rate, and improve the quality of life.
Topics: Humans; Atrial Fibrillation; Drugs, Chinese Herbal; Male; Female; Middle Aged; Anti-Arrhythmia Agents; Dronedarone; Catheter Ablation; Treatment Outcome; Recurrence; Aged; Drug Therapy, Combination; Capsules
PubMed: 38669399
DOI: 10.1097/MD.0000000000037918 -
American Heart Journal Aug 2024Recurrent ventricular tachycardia (VT) in patients with prior myocardial infarction is associated with adverse quality of life and clinical outcomes, despite the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recurrent ventricular tachycardia (VT) in patients with prior myocardial infarction is associated with adverse quality of life and clinical outcomes, despite the presence of implanted defibrillators (ICDs). Suppression of recurrent VT can be accomplished with antiarrhythmic drug therapy or catheter ablation. The Ventricular Tachycardia Antiarrhythmics or Ablation In Structural Heart Disease 2 (VANISH2) trial is designed to determine whether ablation is superior to antiarrhythmic drug therapy as first line therapy for patients with ischemic cardiomyopathy and VT.
METHODS
The VANISH2 trial enrolls patients with prior myocardial infarction and VT (with one of: ≥1 ICD shock; ≥3 episodes treated with antitachycardia pacing (ATP) and symptoms; ≥5 episodes treated with ATP regardless of symptoms; ≥3 episodes within 24 hours; or sustained VT treated with electrical cardioversion or pharmacologic conversion). Enrolled patients are classified as either sotalol-eligible, or amiodarone-eligible, and then are randomized to either catheter ablation or to that antiarrhythmic drug therapy, with randomization stratified by drug-eligibility group. Drug therapy, catheter ablation procedures and ICD programming are standardized. All patients will be followed until two years after randomization. The primary endpoint is a composite of mortality at any time, appropriate ICD shock after 14 days, VT storm after 14 days, and treated sustained VT below detection of the ICD after 14 days. The outcomes will be analyzed according to the intention-to-treat principle using survival analysis techniques RESULTS: The results of the VANISH2 trial are intended to provide data to support clinical decisions on how to suppress VT for patients with prior myocardial infarction.
CLINICALTRIALS
gov registration NCT02830360.
Topics: Humans; Tachycardia, Ventricular; Anti-Arrhythmia Agents; Catheter Ablation; Cardiomyopathies; Myocardial Ischemia; Male; Female; Defibrillators, Implantable; Middle Aged; Amiodarone; Treatment Outcome; Sotalol; Combined Modality Therapy
PubMed: 38649085
DOI: 10.1016/j.ahj.2024.04.009 -
Advances in Medical Sciences Apr 2024Little is known about the effectiveness of pharmacological cardioversion (PCV) with antazoline in comparison to flecainide. The aim of this study was to compare the...
PURPOSE
Little is known about the effectiveness of pharmacological cardioversion (PCV) with antazoline in comparison to flecainide. The aim of this study was to compare the effectiveness of antazoline in restoring sinus rhythm (SR) versus amiodarone, flecainide and propafenone in a group of emergency department (ED) patients.
MATERIALS/METHODS
This was a single-centre retrospective analysis of patient records from an ED in a large hospital in Poland. We analysed a total of 1878 patient records, divided based on the anti-arrhythmic drug (AAD) administered during PCV: antazoline (n = 1080), antazoline + β-blocker (n = 479), amiodarone (n = 129), flecainide (n = 102), propafenone (n = 88). Of the patients, 63.5 % were female (median 65 years, [19-100]).
RESULTS
The percentage of successful PCV was significantly higher in the antazoline group (84.3 %) than in the antazoline + β-blocker (75.8 %, p = 0.0001), propafenone (75.6 %, p = 0.0364) and amiodarone (68.8 %, p < 0.0001) groups. Post-hoc analysis revealed that patients who received PCV with antazoline, antazoline + β-blocker, flecainide and propafenone had significantly shorter time to SR than those who received amiodarone (p < 0.0001). Univariate regression analysis revealed that patients who underwent PCV with antazoline were almost twice as likely to return to SR compared to the other groups (p < 0.0001, OR 1.81, 95 % CI 1.44-2.27).
CONCLUSIONS
This is the first study comparing the effectiveness of antazoline in PCV versus flecainide in addition to the previously studied amiodarone and propafenone. Our results indicate that antazoline is more effective in restoring SR than amiodarone, flecainide and propafenone. In addition, antazoline restored SR significantly faster than amiodarone or propafenone.
PubMed: 38649031
DOI: 10.1016/j.advms.2024.04.003 -
Resuscitation Plus Jun 2024To explore potential predictors of national out-of-hospital cardiac arrest (OHCA) survival, including health system developments and the COVID pandemic in Ireland.
AIM
To explore potential predictors of national out-of-hospital cardiac arrest (OHCA) survival, including health system developments and the COVID pandemic in Ireland.
METHODS
National level OHCA registry data from 2012 through to 2020, relating to unwitnessed, and bystander witnessed OHCA were interrogated. Logistic regression models were built by including predictors through stepwise variable selection and enhancing the models by adding pairwise interactions that improved fit. Missing data sensitivity analyses were conducted using multiple imputation.
RESULTS
The data included 18,177 cases. The final model included seventeen variables. Of these nine variables were involved in pairwise interactions. The COVID-19 period was associated with reduced survival (OR 0.61, 95%CI 0.43, 0.87), as were increasing age in years (OR 0.96, 95% CI 0.96, 0.97) and call response interval in minutes (OR 0.97, 95% CI 0.96, 0.99). Amiodarone administration (OR 3.91, 95% CI 2.80, 5.48), urban location (OR 1.40, 95% CI 1.12, 1.77), and chronological year over time (OR 1.14, 95% CI 1.08, 1.20) were associated with increased survival.
CONCLUSIONS
National survival from OHCA has significantly increased incrementally over time in Ireland. The COVID-19 pandemic was associated with decreased survival even after accounting for potential disruption to key elements of bystander and EMS care. Further research is needed to understand and address the discrepancy between urban and rural OHCA survival. Information concerning pre-event patient health status and inpatient care process may yield important additional insights in future.
PubMed: 38646094
DOI: 10.1016/j.resplu.2024.100641 -
Luminescence : the Journal of... Apr 2024In an acidic buffered solution, erythrosine B can react with amiodarone to form an association complex, which not only generates great enhancement in resonance Rayleigh...
In an acidic buffered solution, erythrosine B can react with amiodarone to form an association complex, which not only generates great enhancement in resonance Rayleigh scattering (RRS) spectrum of erythrosine B at 346.5 nm but also results in quenching of fluorescence spectra of erythrosine B at λ = 550.4 nm/λ = 528.5 nm. In addition, the formed erythrosine B-amiodarone complex produces a new absorbance peak at 555 nm. The spectral characteristics of the RRS, absorbance, and fluorescence spectra, as well as the optimum analytical conditions, were studied and investigated. As a result, new spectroscopic methods were developed to determine amiodarone by utilizing erythrosine B as a probe. Moreover, the ICH guidelines were used to validate the developed RRS, photometric, and fluorimetric methods. The enhancements in the absorbance and the RRS intensity and the decrease in the fluorescence intensity of the used probe were proportional to the concentration of amiodarone in ranges of 2.5-20.0, 0.2-2.5, and 0.25-1.75 μg/mL, respectively. Furthermore, limit of detection values were 0.52 ng/mL for the spectrophotometric method, 0.051 μg/mL for the RRS method, and 0.075 μg/mL for the fluorimetric method. Moreover, with good recoveries, the developed spectroscopic procedures were applied to analyze amiodarone in its commercial tablets.
Topics: Amiodarone; Erythrosine; Spectrometry, Fluorescence; Anti-Arrhythmia Agents; Molecular Structure
PubMed: 38644515
DOI: 10.1002/bio.4748 -
JACC. Clinical Electrophysiology Jun 2024Extracellular vesicles (EVs) isolated from human heart-derived cells have shown promise in suppressing inflammation and fibroblast proliferation. However, their precise... (Comparative Study)
Comparative Study
BACKGROUND
Extracellular vesicles (EVs) isolated from human heart-derived cells have shown promise in suppressing inflammation and fibroblast proliferation. However, their precise benefits in atrial fibrillation (AF) prevention and the role of their antifibrotic/anti-inflammatory properties remain unclear.
OBJECTIVES
The purpose of this study was to conduct a head-to-head comparison of antiarrhythmic strategies to prevent postoperative AF using a rat model of sterile pericarditis. Specifically, we aimed to assess the efficacy of amiodarone (a classic antiarrhythmic drug), colchicine (an anti-inflammatory agent), and EVs derived from human heart-derived cells, which possess anti-inflammatory and antifibrotic properties, on AF induction, inflammation, and fibrosis progression.
METHODS
Heart-derived cells were cultured from human atrial appendages under serum-free xenogen-free conditions. Middle-aged Sprague Dawley rats were randomized into different groups, including sham operation, sterile pericarditis with amiodarone treatment, sterile pericarditis with colchicine treatment (2 dose levels), and sterile pericarditis with intra-atrial injection of EVs or vehicle. Invasive electrophysiological testing was performed 3 days after surgery before sacrifice.
RESULTS
Sterile pericarditis increased the likelihood of inducing AF. Colchicine and EVs exhibited anti-inflammatory effects, but only EV treatment significantly reduced AF probability, whereas colchicine showed a positive trend without statistical significance. EVs and high-dose colchicine reduced atrial fibrosis by 46% ± 2% and 26% ± 2%, respectively. Amiodarone prevented AF induction but had no effect on inflammation or fibrosis.
CONCLUSIONS
In this study, both amiodarone and EVs prevented AF, whereas treatment with colchicine was ineffective. The additional anti-inflammatory and antifibrotic effects of EVs suggest their potential as a comprehensive therapeutic approach for AF prevention, surpassing the effects of amiodarone or colchicine.
Topics: Atrial Fibrillation; Colchicine; Amiodarone; Animals; Rats; Rats, Sprague-Dawley; Fibrosis; Anti-Arrhythmia Agents; Humans; Male; Heart Atria; Inflammation; Postoperative Complications; Anti-Inflammatory Agents; Pericarditis; Extracellular Vesicles; Disease Models, Animal; Cells, Cultured
PubMed: 38639701
DOI: 10.1016/j.jacep.2024.02.019 -
Cardiology Clinics May 2024The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify... (Review)
Review
The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of β-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.
Topics: Humans; Heart Arrest; Anti-Arrhythmia Agents; Amiodarone; Lidocaine; Epinephrine; Ventricular Fibrillation; Cardiopulmonary Resuscitation
PubMed: 38631795
DOI: 10.1016/j.ccl.2024.02.012 -
Cureus Mar 2024The objective of this study was to compare the impact of amiodarone and lidocaine on survival and neurological outcomes following cardiac arrest. A systematic review of... (Review)
Review
The objective of this study was to compare the impact of amiodarone and lidocaine on survival and neurological outcomes following cardiac arrest. A systematic review of randomized controlled trials (RCTs) as well as cohort and cross-sectional trials was undertaken, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Potential relevant studies were searched in databases, including PubMed, Embase, Cochrane Library, and Web of Science, from the beginning of databases to February 15, 2024. Outcomes assessed in this study were survival to hospital discharge, survival to hospital admission or 24 hours, favorable neurological outcomes, and return of spontaneous circulation (ROSC). A total of seven studies (five observational and two RCTs) were included in this meta-analysis encompassing 19,081 patients with cardiac arrest. Pooled analysis showed no difference between amiodarone and lidocaine in terms of survival to hospital discharge (odds ratio (OR): 0.88, 95% confidence interval (CI): 0.75 to 1.04), ROSC (OR: 0.94, 95% CI: 0.84 to 1.05, p-value: 0.25), favorable neurological outcomes (OR: 0.88, 95% CI: 0.66 to 1.17, p-value: 0.38), and survival to 24 hours (OR: 0.82, 95% CI: 0.55 to 1.21, p-value: 0.31). While lidocaine demonstrated a slight survival advantage, the differences were statistically insignificant. Similarly, no significant variations were observed in ROSC incidence, neurological outcomes, or survival at 24 hours. These findings align with current guidelines but underscore the necessity for further rigorous RCTs to provide conclusive recommendations.
PubMed: 38623114
DOI: 10.7759/cureus.56037 -
Pharmacological Reports : PR Jun 2024Amiodarone (AMIO) is an antiarrhythmic drug with the pKa in the physiological range. Here, we explored how mild extracellular pH (pHe) changes shape the interaction of...
BACKGROUND
Amiodarone (AMIO) is an antiarrhythmic drug with the pKa in the physiological range. Here, we explored how mild extracellular pH (pHe) changes shape the interaction of AMIO with atrial tissue and impact its pharmacological properties in the classical model of sea anemone sodium channel neurotoxin type 2 (ATX) induced late sodium current (I) and arrhythmias.
METHOD
Isolated atrial cardiomyocytes from male Wistar rats and human embryonic kidney cells expressing SCN5A Na channels were used for patch-clamp experiments. Isolated right atria (RA) and left atria (LA) tissue were used for bath organ experiments.
RESULTS
A more acidophilic pHe caused negative inotropic effects on isolated RA and LA atrial tissue, without modification of the pharmacological properties of AMIO. A pHe of 7.0 changed the sodium current (I) related components of the action potential (AP), which was enhanced in the presence of AMIO. ATXinduced arrhythmias in isolated RA and LA. Also, ATX prolonged the AP duration and enhanced repolarization dispersion in isolated cardiomyocytes in both pHe 7.4 and pHe 7.0. Pre-incubation of the isolated RA and LA and isolated atrial cardiomyocytes with AMIO prevented arrhythmias induced by ATX only at a pHe of 7.0. Moreover, AMIO was able to block I induced by ATX only at a pHe of 7.0.
CONCLUSION
The pharmacological properties of AMIO concerning healthy rat atrial tissue are not dependent on pHe. However, the prevention of arrhythmias induced by I is pHe-dependent. The development of drugs analogous to AMIO with charge stabilization may help to create more effective drugs to treat arrhythmias related to the I.
Topics: Animals; Amiodarone; Anti-Arrhythmia Agents; Male; Rats, Wistar; Humans; Rats; Myocytes, Cardiac; Action Potentials; Heart Atria; Hydrogen-Ion Concentration; Arrhythmias, Cardiac; NAV1.5 Voltage-Gated Sodium Channel; HEK293 Cells; Sodium; Patch-Clamp Techniques; Cnidarian Venoms
PubMed: 38619735
DOI: 10.1007/s43440-024-00597-2