-
CJEM Jan 2021
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans
PubMed: 33683610
DOI: 10.1007/s43678-020-00019-1 -
Heart Rhythm O2 Dec 2021Antiarrhythmic therapy for recurrent ventricular arrhythmias in patients who have undergone catheter ablation, and in whom amiodarone and/or beta-blockers were...
BACKGROUND
Antiarrhythmic therapy for recurrent ventricular arrhythmias in patients who have undergone catheter ablation, and in whom amiodarone and/or beta-blockers were ineffective or contraindicated, is a controversial issue.
OBJECTIVE
The present study sought to evaluate the efficacy and tolerability of oral procainamide in patients with recurrent ventricular arrhythmias when the standard therapy strategy had failed.
METHODS
All patients treated with procainamide for recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) in our institution between January 2010 and May 2019 were enrolled. The primary endpoint was the total number of implantable cardioverter-defibrillator (ICD) interventions after the beginning of procainamide therapy. Secondary endpoints were the total number of VTs and VFs recorded on the ICDs' controls and discontinuation of therapy. The events occurring during procainamide treatment were compared with a matched-duration period before the initiation of therapy with procainamide. Patients therefore served as self-controls.
RESULTS
A total of 34 consecutive patients (32 male, 94.1%; mean age 74.4 ± 9.7 years) were included in the retrospective analysis. The mean time of procainamide treatment was 12.9 ± 13.7 months (median 9 [2-20] months). The mean dose of procainamide was 1207 ± 487 mg/day. Procainamide therapy significantly decreased ICD interventions (median 5 [0-22.5] vs 15.5 [3-32.25], < .05). Procainamide also decreased the total number of VT/VF episodes (median 5.5 [0.75-30] vs 19 [7.5-30], < .05). Only 3 patients (8.8%) presented severe side effects (dyspnea or hypotension), requiring discontinuation of therapy.
CONCLUSION
Oral procainamide was associated with a significant decrease in ICD therapies and ventricular arrhythmias, showing an acceptable profile of tolerability.
PubMed: 34988535
DOI: 10.1016/j.hroo.2021.10.002 -
Journal of Chromatography. B,... Jan 2023N-glycans in glycoproteins can affect physicochemical properties of proteins; however, some reported N-glycan structures are inconsistent depending on the type of...
Peptide-N-glycosidase F or A treatment and procainamide-labeling for identification and quantification of N-glycans in two types of mammalian glycoproteins using UPLC and LC-MS/MS.
BACKGROUND
N-glycans in glycoproteins can affect physicochemical properties of proteins; however, some reported N-glycan structures are inconsistent depending on the type of glycoprotein or the preparation methods.
OBJECTIVE
To obtain consistent results for qualitative and quantitative analyses of N-glycans, N-glycans obtained by different preparation methods were compared for two types of mammalian glycoproteins.
METHODS
N-glycans are released by peptide-N-glycosidase F (PF) or A (PA) from two model mammalian glycoproteins, bovine fetuin (with three glycosylation sites) and human IgG (with a single glycosylation site), and labeled with a fluorescent tag [2-aminobenzamide (AB) or procainamide (ProA)]. The structure and quantity of each N-glycan were determined using UPLC and LC-MS/MS.
RESULTS
The 21 N-glycans in fetuin and another 21 N-glycans in IgG by either PF-ProA or PA-ProA were identified using LC-MS/MS. The N-glycans in fetuin (8-13 N-glycans were previously reported) and in IgG (19 N-glycans were previously reported), which could not be identified by using the widely used PF-AB, were all identified by using PF-ProA or PA-ProA. The quantities (%) of the N-glycans (>0.1 %) relative to the total amount of N-glycans (100 %) obtained by AB- and ProA-labeling using LC-MS/MS had a similar tendency. However, the absolute quantities (pmol) of the N-glycans estimated using UPLC and LC-MS/MS were more efficiently determined with ProA-labeling than with AB-labeling. Thus, PF-ProA or PA-ProA allows for more effective identification and quantification of N-glycans than PF-AB in glycoprotein, particularly bovine fetuin. This study is the first comparative analysis for the identification and relative and absolute quantification of N-glycans in glycoproteins with PF-ProA and PA-ProA using UPLC and LC-MS/MS.
Topics: Animals; Cattle; Humans; Chromatography, Liquid; Glycoproteins; Immunoglobulin G; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; Peptides; Polysaccharides; Procainamide; Tandem Mass Spectrometry
PubMed: 36493594
DOI: 10.1016/j.jchromb.2022.123538 -
Pacing and Clinical Electrophysiology :... Dec 2021Late potentials (LPs) identified on the signal averaged electrocardiogram (SAECG) are a marker for an increased risk of arrhythmias in Brugada syndrome (BrS)....
BACKGROUND
Late potentials (LPs) identified on the signal averaged electrocardiogram (SAECG) are a marker for an increased risk of arrhythmias in Brugada syndrome (BrS). Procainamide is a sodium channel blocker used to diagnose BrS. The effects of Procainamide on the SAECG in those with BrS and the significance of Procainamide-induced LPs are unknown.
METHODS
Procainamide provocation was performed for suspected BrS with 12-lead and SAECG pre- and post-infusion. Filtered QRS duration (fQRSd), duration of low amplitude signals <40 μV (LAS40) and root-mean-square voltage in the terminal 40 ms (RMS40) were determined.
RESULTS
Data from 150 patients were included in the analysis (mean age 44.5 years, 109 males). Procainamide increased fQRSd (Pre 118.8 ± 10.5 ms, post 121.2 ± 10.2 ms, p < 0.001) and LAS40 (Pre 38.7 ± 9.8 ms, post 40.2 ± 10.5 ms, p = 0.005) and decreased RMS40 (Pre 24.6 ± 12 ms, post 22.8 ± 12 ms, p = 0.002). LPs were present in 68/150 (45%) at baseline. Fifteen patients with negative baseline SAECGs had LPs unmasked by Procainamide, but six patients had LPs at baseline that were no longer present following Procainamide. Comparing those with normal hearts (n = 48) to those with a final diagnosis of BrS (n = 38), Procainamide prolonged fQRSd to a greater extent in those with BrS. Comparing those with Procainamide-induced LPs to those with no LPs at any time did not highlight any aspect of phenotype and did not correlate with a history of ventricular arrhythmias.
CONCLUSIONS
Procainamide influences the SAECG, provoking LPs in a small proportion of patients. However, there is no evidence that Procainamide-induced LPs provide additional diagnostic information or aid risk stratification.
Topics: Adult; Brugada Syndrome; Electrocardiography; Female; Humans; Male; Middle Aged; Procainamide; Voltage-Gated Sodium Channel Blockers
PubMed: 34648655
DOI: 10.1111/pace.14379 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2017Aconite poisoning is relatively rare but is frequently complicated by ventricular dysrhythmias, which may be fatal. Molecular basis of aconite alkaloid ventricular... (Review)
Review
INTRODUCTION
Aconite poisoning is relatively rare but is frequently complicated by ventricular dysrhythmias, which may be fatal. Molecular basis of aconite alkaloid ventricular arrhythmogenicity: Aconite exerts its toxic effects due to the presence of an admixture of alkaloids present in all parts of the plant. The major target of these aconite alkaloids is the fast voltage-gates sodium channel, where they cause persistent activation. This blockade of the channel in the activated state promotes automaticity within the ventricular myocardium and the generation of ventricular arrhythmias. Aconitine-induced arrhythmias: Aconite alkaloids are known to cause many different types of disturbance of heart rhythm. However, this focused review specifically looks at ventricular rhythm disturbances, namely ventricular ectopy, ventricular tachycardia, torsades des pointes and ventricular fibrillation.
OBJECTIVE
The objective of this review was to identify the outcome of anti-dysrhythmic strategies from animal studies and case reports in humans in order to guide the management of ventricular dysrhythmias in aconite poisoning in humans.
METHODS
A review of the literature in English was conducted in PubMed and Google Scholar from 1966 to July 2016 using the search terms "aconite/aconitine"; "aconite/aconitine + poisoning" and "aconite/aconitine + dysrhythmia". 168 human case-reports and case-series were identified by these searches, of which 103 were rejected if exposure to aconite did not result in ventricular dysrhythmias, if it was uncertain as to whether aconite had been ingested, if other agents were co-ingested, if there was insufficient information to determine the type of treatments administered or if there was insufficient information to determine outcome. Thus, 65 case reports of probable aconite poisoning that resulted in ventricular dysrhythmias were identified. Toxicokinetic data in aconite poisoning: Data were only available in three papers; the presence of ventricular rhythm disturbances directly correlated with the concentration of aconite alkaloids in the plasma.
MANAGEMENT
54 of 65 cases developed ventricular tachycardia, six developed torsades des pointes, 15 patients developed ventricular fibrillation, 10 developed ventricular ectopics and one developed a broad complex tachycardia not otherwise specified; each dysrhythmia was regarded as separate and patients may have had more than one dysrhythmia. 10 patients died, giving a mortality of 15%. In total, 147 treatments were administered to 65 patients. 46 of the interventions were assessed by the authors as having been associated with successful restoration of sinus rhythm. Flecainide administration was accompanied by dysrhythmia termination in six of seven cases. Mexiletine was connected with correcting dysrhythmias in 3 of 3 cases. Procainamide administration was associated with return to sinus rhythm in 2 of 2 cases. Prolonged cardio-pulmonary resuscitation was administered to 15 patients where it was associated with a return to sinus rhythm in nine of these. Amiodarone was linked to success in correcting dysrhythmias in 11 of 20 cases. Cardiopulmonary bypass use was associated with a return to sinus rhythm in four out of six cases. Epinephrine was documented as being employed on four occasions, and was associated with a restoration of sinus rhythm on two of these. Magnesium sulphate administration was accompanied by dysrhythmia termination in two of nine cases. Direct cardioversion was associated with a return of sinus rhythm in 5 of 30 cases. However, it is not certain whether the drug treatment influenced the course of the dysrhythmia.
CONCLUSIONS
Based on the evidence available from human case reports, flecainaide or amiodarone appear to be more associated with a return to sinus rhythm than lidocaine and/or cardioversion, although it is not established whether the administration of treatment caused reversion to normal sinus rhythm. The potential beneficial effects of amiodarone were not observed in animal studies. This may be due to intra-species differences between ion channels or relate to the wider cardiovascular toxicity of aconite that extends beyond arrhythmias. Prolonged cardiopulmonary resuscitation and cardiopulmonary bypass should be considered as an integral part of good clinical care as "time-buying" strategies to allow the body to excrete the toxic alkaloids. There may also be a role for mexiletine, procainamide and magnesium sulphate.
Topics: Aconitum; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium; Cardiopulmonary Bypass; Cardiopulmonary Resuscitation; Databases, Factual; Disease Models, Animal; Electric Countershock; Heart Conduction System; Humans; Neurons; Poisoning; Sodium; Sodium Channels; Toxicokinetics; Ventricular Fibrillation
PubMed: 28421842
DOI: 10.1080/15563650.2017.1291944 -
Frontiers in Medicine 2015The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin... (Review)
Review
The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders.
PubMed: 25688346
DOI: 10.3389/fmed.2015.00003 -
Analytical Chemistry Mar 2022Mass spectrometry-based shotgun glycomics (MS-SG) is a rapid, sensitive, label-, and immobilization-free approach for the discovery of natural ligands of glycan-binding...
Mass spectrometry-based shotgun glycomics (MS-SG) is a rapid, sensitive, label-, and immobilization-free approach for the discovery of natural ligands of glycan-binding proteins (GBPs). To perform MS-SG, natural libraries of glycans derived from glycoconjugates in cells or tissues are screened against a target GBP using catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS). Because glycan concentrations are challenging to determine, ligand affinities cannot be directly measured. In principle, relative affinities can be ranked by combining CaR-ESI-MS data with relative concentrations established by hydrophilic interaction liquid chromatography (HILIC) performed on the fluorophore-labeled glycan library. To validate this approach, as well as the feasibility of performing CaR-ESI-MS directly on labeled glycans, libraries of labeled -glycans extracted from the human monocytic U937 cells or intestinal tissues were labeled with 2-aminobenzamide (2-AB), 2-aminobenzoic acid (2-AA), or procainamide (proA). The libraries were screened against plant and human GBPs with known specificities for α2-3- and α2-6-linked sialosides and quantified by HILIC. Dramatic differences, in some cases, were found for affinity rankings obtained with libraries labeled with different fluorophores, as well as those produced using the combined unlabeled/labeled library approach. The origin of these differences could be explained by differential glycan labeling efficiencies, the impact of specific labels on glycan affinities for the GBPs, and the relative efficiency of release of ligands from GBPs in CaR-ESI-MS. Overall, the results of this study suggest that the 2-AB(CaR-ESI-MS)/2-AB(HILIC) combination provides the most reliable description of the binding specificities of GBPs for -glycans and is recommended for MS-SG applications.
Topics: Carrier Proteins; Chromatography, Liquid; Fluorescent Dyes; Glycomics; Humans; Ligands; Polysaccharides; Proteins; Spectrometry, Mass, Electrospray Ionization
PubMed: 35302744
DOI: 10.1021/acs.analchem.1c04779 -
Molecules (Basel, Switzerland) Nov 2018Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source...
Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source is demonstrated as a simple, facile and clean approach for the synthesis of substituted anilines and selected pharmaceutically relevant compounds. The scope of mechanochemical CTH is broad, as the reduction conditions tolerate various functionalities, for example nitro, amino, hydroxy, carbonyl, amide, urea, amino acid and heterocyclic. The presented methodology was also successfully integrated with other types of chemical reactions previously carried out mechanochemically, such as amide bond formation by coupling amines with acyl chlorides or anhydrides and click-type coupling reactions between amines and iso(thio)cyanates. In this way, we showed that active pharmaceutical ingredients Procainamide and Paracetamol could be synthesized from the respective nitro-precursors on milligram and gram scale in excellent isolated yields.
Topics: Aniline Compounds; Catalysis; Hydrocarbons, Aromatic; Hydrogenation; Nitro Compounds; Spectroscopy, Fourier Transform Infrared
PubMed: 30513686
DOI: 10.3390/molecules23123163 -
JACC. Clinical Electrophysiology Feb 2019This study sought to compare the differences between procainamide and flecainide to stress the His-Purkinje system during electrophysiological study (EPS) in patients...
OBJECTIVES
This study sought to compare the differences between procainamide and flecainide to stress the His-Purkinje system during electrophysiological study (EPS) in patients with syncope and bundle branch block (BBB).
BACKGROUND
Patients with syncope and BBB are at risk of developing atrioventricular block. EPS is recommended including class I drug challenge to unmask His-Purkinje disease in cases with baseline normal His-ventricular interval. There is little data on differences between different class I drugs.
METHODS
This was a prospective study of all consecutive patients undergoing EPS for syncope and BBB at a single center (January 1, 2012 to June 30, 2017). Of those patients with negative baseline EPS, 2 cohorts were compared: group A (historical cohort: procainamide) and group B (flecainide).
RESULTS
During the study, 271 patients (age 73.9 ± 12.1 years, 64.9% male, QRS duration: 139.4 ± 13.9 ms) underwent EPS. In 166, baseline EPS was negative and class I drug challenge was performed (90 procainamide, 76 flecainide). The final value and percentage increase in the His-ventricular interval (76 ± 16 ms vs. 64 ± 10 ms and 22.5 ± 6.2% vs. 11.8 ± 5.3%; p < 0.001) and diagnostic yield (14.5% vs. 7.8%, p = 0.04) were higher with flecainide. No differences were found in baseline characteristics. During follow-up (25.8 ± 6.3 months), 39 patients (24.8%) with negative EPS (19.2% with flecainide vs. 30.1% with procainamide: relative risk: 5.1; 95% confidence interval: 2.6 to 10.2; p < 0. 001) received a pacemaker.
CONCLUSIONS
Flecainide has a higher diagnostic yield than does procainamide in patients with BBB, syncope, and negative baseline EPS due to a greater increase of the His-ventricular interval. Additionally, there is a lesser need for pacemaker implantation in patients in whom the class I drug test using flecainide was negative.
Topics: Aged; Aged, 80 and over; Bundle-Branch Block; Electrocardiography; Electrophysiologic Techniques, Cardiac; Female; Flecainide; Heart Conduction System; Humans; Male; Middle Aged; Procainamide; Syncope
PubMed: 30784693
DOI: 10.1016/j.jacep.2018.09.015 -
Hospital Pharmacy Nov 2017The objective of this study was to evaluate the chemical stability of procainamide hydrochloride, 100 mg/mL, when repackaged in clear glass vials or diluted to 3 mg/mL...
OBJECTIVES
The objective of this study was to evaluate the chemical stability of procainamide hydrochloride, 100 mg/mL, when repackaged in clear glass vials or diluted to 3 mg/mL with normal saline and packaged in polyvinyl chloride (PVC) bags when stored at either 23°C and exposed to light (ETL) or 5°C and protected from light (PFL).
METHODS
Solutions were assayed using a stability-indicating high-performance liquid chromatography method. Samples (5 mL) were collected from triplicate containers on days 0, 7, 14, 21, 28, 56, 91, and 193. Color/clarity and pH changes were also monitored at each time interval.
RESULTS
During the study, all samples remained clear and there was only a slight pH change. The color of the solutions stored at 23°C intensified but did not correlate with a significant decrease in concentration, while solutions stored at 5°C remained unchanged. Solutions repackaged in glass vials were stable for 193 days when stored at 23ºC and ETL or 5ºC and PFL. When further diluted to 3 mg/mL with normal saline and packaged in PVC bags, procainamide was also stable for 193 days at either 23ºC and ETL or 5°C and PFL.
CONCLUSIONS
The stability of procainamide, 100 mg/mL, repackaged in clear glass vials was 193 days when stored at either 23ºC and ETL or 5ºC or PFL. If diluted further to 3 mg/mL with normal saline and packaged in PVC bags, the drug was also stable for 193 days at either 23ºC and ETL or 5°C and PFL.
PubMed: 29276243
DOI: 10.1177/0018578717724896