Diagnosis of Brugada Syndrome With a Sodium-Channel-Blocker Test: Who Should Be Tested? Who Should Not?

Intravenous infusion of sodium-channel blockers (SCB) with either ajmaline, flecainide, procainamide, or pilsicainide to unmask the ECG of Brugada syndrome is the drug challenge most commonly used for diagnostic purposes when investigating cases possibly related to inherited arrhythmia syndromes. For a patient undergoing an SCB challenge, the impact of a positive result goes well beyond its diagnostic implications. It is, therefore, appropriate to question who should undergo a SCB test to diagnose or exclude Brugada syndrome and, perhaps more importantly, who should not. We present a critical review of the benefits and drawbacks of the SCB challenge when performed in cardiac arrest survivors, patients presenting with syncope, family members of probands with confirmed Brugada syndrome, and asymptomatic patients with suspicious ECG.

Treatment of lidocaine-refractory ventricular tachycardia using procainamide in an anesthetized horse.

OBJECTIVE: To highlight the use of procainamide as a potential alternative treatment modality in cases of ventricular tachycardia that are refractory to lidocaine and magnesium sulfate. ANIMAL: 1 adult horse weighing 380 kg. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: A 25-year-old Arabian gelding presented with severe colic signs. Due to persistent pain, it was elected to carry out an exploratory laparotomy. During the procedure a diagnosis of severe, unstable ventricular tachycardia was made based on the ECG findings, with an initial heart rate of 195 beats per minute and severe hypotension. TREATMENT AND OUTCOME: Initial treatment consisted of discontinuing dobutamine and the administration of a 2 mg/kg IV lidocaine bolus followed by a continuous rate infusion at 50 µg/kg/min. Twenty grams magnesium sulfate (5 mg/kg) was administered IV in 1 L of lactated Ringer solution as a slow bolus over 30 minutes. Ventricular tachycardia persisted with poor peripheral pulses, a severely dampened arterial waveform, and a MAP of 30 to 45 mm Hg. Two milligrams/kg IV procainamide was administered over 3 minutes, 3 separate times, at 5-minute intervals. Immediately following the third dose sinus rhythm was detected on the ECG, the arterial waveform improved, and MAP increased to 85 mm Hg. CLINICAL RELEVANCE: Ventricular tachycardia is a rare but potentially life-threatening complication in horses undergoing general anesthesia. The potential of this arrhythmia to progress to ventricular fibrillation is of grave concern, as the option to attempt to externally defibrillate horses back to normal sinus rhythm does not exist. This case highlights procainamide as a potential option for cases of ventricular tachycardia that are refractory to more standard treatment modalities.

ACOX1 deficiency-induced lipid metabolic disorder facilitates chronic interstitial fibrosis development in renal allografts.

Chronic interstitial fibrosis presents a significant challenge to the long-term survival of transplanted kidneys. Our research has shown that reduced expression of acyl-coenzyme A oxidase 1 (ACOX1), which is the rate-limiting enzyme in the peroxisomal fatty acid ß-oxidation pathway, contributes to the development of fibrosis in renal allografts. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), which mediate epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) reorganization respectively, thus causing fibrosis in renal allografts. Furthermore, activation of Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) signaling induced ACOX1 downregulation in a DNA methyltransferase 1 (DNMT1)-dependent manner. Overconsumption of PUFA resulted in endoplasmic reticulum (ER) stress, which played a vital role in facilitating ECM reorganization. Supplementation with PUFAs contributed to delayed fibrosis in a rat model of renal transplantation. The study provides a novel therapeutic approach that can delay chronic interstitial fibrosis in renal allografts by targeting the disorder of lipid metabolism.

Development and validation of online SPE purification coupled to HILIC-fluorescence-MS analysis for the characterization of N-glycans.

N-glycans of therapeutic glycoproteins is a critical quality attribute to be addressed. We developed a sensitive method for N-glycan characterization using procainamide (ProcA) labelling and online solid phase extraction (online SPE). N-glycans were enzymatically released, then labeled with ProcA and cleaned up via the online SPE using HILIC chemistry (online HILIC SPE). Two preparation protocols were optimized: a short one (1 h 30) and a long one (18 h). Furthermore, the developed approach was compared to RapiFluor-MS (RFMS) kit (from Waters) and to InstantPC kit (from Agilent) which both include a classical HILIC µElution plate SPE purification. Samples were analyzed using HILIC separation coupled to fluorescence and MS detection (HILIC-FLD-MS) with or without the online HILIC SPE. During the validation, repeatability, intermediate precision, stability, response function and injection volume were tested. Human IgG mix (Multigam®) and NIST mAb standard were used as references as their glycoprofiles are well described. A comparison of three batches of a rituximab biosimilar (Truxima®) and one batch of its originator (MabThera®) was also performed. Online HILIC SPE sample cleanup shows a higher sensitivity and repeatability compared to the classical HILIC µElution SPE. Our online HILIC SPE approach also offers the highest MS signal compared to both commercial kits. However, InstantPC shows the highest FLD signal. The analyses of rituximab samples were in line with the literature showing the efficiency of the method for N-glycan monitoring of biotherapeutics. In conclusion, the results demonstrated the usefulness and ease of application of the developed protocol with the online HILIC SPE purification.

Synthesis and evaluation of 18F-labeled procainamide as a PET imaging agent for malignant melanoma.

Malignant melanoma has an aggressive nature and a high metastatic propensity resulting in the highest mortality rate of any skin cancer. In this study, we synthesized 18F-labeled procainamide (PCA) for detection of melanoma using positron emission tomography (PET), and evaluated its biological characteristics. The non-decay-corrected radiochemical yield of 18F-PCA was 10-15% and its in vitro stability was over 98% for 2 h. At 1 h, cellular uptake of 18F-PCA was 3.8-fold higher in a group with the presence of l-tyrosine than in a non-l-tyrosine-treated group. Furthermore, 18F-PCA permitted visualization of B16F10 (mouse melanoma) xenografts on microPET after intravenous injection, and was retained in the tumor for 60 min, with a high tumor-to-liver uptake ratio. 18F-PCA showed specific melanoma uptake in primary lesions with a high melanin targeting ability in small animal models. 18F-PCA may have potential as a PET imaging agent for direct melanoma detection.

Combination Therapy of Ivabradine with Procainamide for the Management of Pediatric Postoperative Junctional Ectopic Tachycardia.

Pediatric postoperative junctional ectopic tachycardia (JET), although usually self-limited, may lead to significant morbidity and mortality. Anti-arrhythmic medications are often necessary to restore atrioventricular synchrony when non-pharmacological measures fail. Multiple drugs have been described for the management of postoperative JET, with enteral ivabradine being the latest addition. While safe administration of ivabradine has been described in combination with other anti-arrhythmics (amiodarone, flecainide), no study has described the use of ivabradine in conjunction with intravenous procainamide for the management of postoperative JET. Our case report describes the safe use of ivabradine and procainamide combination therapy in a young patient.

Procainamide-Provoked Brugada Pattern in a Patient Presenting with New-Onset Atrial Fibrillation or Flutter: When Does it Matter?

BACKGROUND: Brugada syndrome (BrS) is an inherited disease that can lead to sudden cardiac death. Medications, such as antidysrhythmics, and fevers can unmask or induce the Brugada pattern on an electrocardiogram (ECG). This case report highlights a patient who developed drug-induced Brugada type I pattern after a procainamide infusion for the treatment of new-onset atrial fibrillation (AF) or flutter and discusses the implications for this incidental but potentially lethal finding. CASE REPORT: We report a case of a young man who presented to the emergency department (ED) with new-onset AF with rapid ventricular response that began within 12 h of presentation. ED treatments included a crystalloid IV fluid bolus, diltiazem pushes, synchronized electrical cardioversion, and a procainamide infusion. After the procainamide infusion, the patient developed ECG findings consistent with Brugada pattern. Both the AF and Brugada pattern resolved spontaneously within 24 h. The patient was discharged without implantable cardioverter defibrillator placement due to presumed isolated procainamide-induced Brugada pattern and lack of concerning features, such as inducible dysrhythmia during electrophysiology study, family history of sudden death, and history of syncope. The patient was counseled to follow-up with genetics and avoid BrS-inducing medications. WHY SHOULD AN EMERGENCY PHYSICIANS BE AWARE OF THIS?: Procainamide, an option for the treatment of AF in the ED, can provoke Brugada pattern. If encountered, it is important to recall that some patients may not be diagnosed with BrS if determined to be low risk according to the Shanghai criteria. All patients should be referred to cardiology for further evaluation.

Light-induced synthesis of silver nanoprisms as a surface-enhanced Raman scattering substrate for N-acetyl procainamide drug quantification.

Triangle-shaped silver nanoprisms (AgNPMs) were prepared by a photo-induced method through a seed-mediated growth process and were successfully employed as an ultra-sensitive surface-enhanced Raman scattering (SERS) substrate for the detection of the chemotherapeutic N-acetyl procainamide (NAPA) compound. The transformation of the morphology of the nanoprisms substrate could be noted with a remarkable change in color, possessing an average size of 95 nm. The shape-modified AgNPMs exhibited interesting optical characteristics owing to the truncated dual edges, which led to a pronounced longitudinal localized surface plasmonic resonance (LLSPR) behavior. The nanoprisms-based SERS substrate demonstrated an outstanding sensitivity for NAPA in aqueous solutions with the lowest ever reported detection limit of 0.5 × 10-13 M corresponding to excellent recovery and stability. A steady linear response with a broad dynamic range (10-4-10-12 M) and an R2 of 0.945 was also achieved. The results proved that the NPMs demonstrated excellent efficiency, reproducibility (97%), and stability (30 days) with a superior Raman signal enhancement reaching an ultralow detection limit of 0.5 × 10-13 M compared to the nanosphere particles which could show an LOD of 0.5 × 10-9 M.

Generic detection of organophosphorus nerve agent adducts to butyrylcholinesterase in plasma using liquid chromatography-tandem mass spectrometry combined with an improved procainamide-gel separation and pepsin digestion method.

Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be applied to confirm exposure in humans. A sensitive method for generic detection of G- and V-series OPNA adducts to BChE in plasma was developed by combining an improved procainamide-gel separation (PGS) and pepsin digestion protocol with ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Residual matrix interferences from prior PGS purification of OPNA-BChE adducts from plasma were found to be a critical cause of significantly reduced UHPLC-MS/MS detection sensitivity. In our developed on-column PGS approach, the matrix interference was successfully removed by adding an appropriate concentration of NaCl to the washing buffer, and it could capture ≥92.5% of the BChE in plasma. The lower pH value and the longer digestion time in all previous pepsin digestion methods were found to be a key accelerated aging factor of several adducts such as tabun (GA)-, cyclohexylsarin (GF)-, and soman (GD)-BChE nonapeptide adducts, making them difficult to detect. The aging event of several OPNA-BChE nonapeptide adducts was so successfully addressed that the formic acid level in enzymatic buffer and digestion time were lowered to 0.05% (pH 2.67) and 0.5 h, respectively, and the post-digestion reaction was immediately terminated. The improved condition parameters were optimal for pepsin digestion of all types of OPNA-BChE adducts into their individual unaged nonapeptide adducts with the highest yields, expanding the applicability of the method. The method had a nearly one-fold decrease in sample preparation time through the reduction of digestion time and removal of ultrafiltration procedure after digestion. The limit of identification (LOI) were determined respectively as 0.13 ng mL-1, 0.28 ng mL-1, 0.50 ng mL-1, 0.41 ng mL-1 and 0.91 ng mL-1 for VX-, sarin (GB)-, GA-, GF-, and GD-exposed human plasma, being low exposure value compared to previously documented approaches. The approach was utilized to fully characterize the adducted (aged and unaged) BChE levels of five OPNAs in a series of their individual exposed concentration (1.00-400 nM) of plasma sample, and successfully detect OPNA exposure from all unknown plasma samples from OPCW's second and third biomedical proficiency tests. The OPNA-BChE adducts, their aged adducts, and unadducted BChE from OPNA-exposed plasma can simultaneously be measured using the method. The study provides a recommended diagnostic tool for generic verification of any OPNA exposure with high confidence by detecting its corresponding BChE adduct.

Synthesis of 4-Amino-N-[2 (diethylamino)Ethyl]Benzamide Tetraphenylborate Ion-Associate Complex: Characterization, Antibacterial and Computational Study.

The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2 (diethylamino) ethyl] benzamide, chloride salt, and procainamide in deionized water at room temperature through an ion-associate reaction (green chemistry) at room temperature, and characterized by several physicochemical methods. The formation of ion-associate complex between bio-active molecules and/or organic molecules is crucial to comprehending the relationships between bioactive molecules and receptor interactions. The solid complex was characterized by infrared spectra, NMR, elemental analysis, and mass spectrometry, indicating the formation of ion-associate or ion-pair complex. The complex under study was examined for antibacterial activity. The ground state electronic characteristics of the S1 and S2 complex configurations were computed using the density functional theory (DFT) approach, using B3LYP level 6-311 G(d,p) basis sets. R2 = 0.9765 and 0.9556, respectively, indicate a strong correlation between the observed and theoretical 1H-NMR, and the relative error of vibrational frequencies for both configurations was acceptable, as well. HOMO and LUMO frontier molecular orbitals and molecular electrostatics using the optimized were used to obtain a potential map of the chemical. The n → π* UV absorption peak of the UV cutoff edge was detected for both configurations of the complex. Spectroscopic methods were structures used to characterize the structure (FT-IR and 1HNMR). In the ground state, DFT/B3LYP/6-311G(d,p) basis sets were used to determine the electrical and geometric properties of the S1 and S2 configurations of the title complex. Comparing the observed and calculated values for the S1 and S2 forms, the HOMO-LUMO energy gap of compounds was 3182 and 3231 eV, respectively. The small energy gap between HOMO and LUMO indicated that the compound was stable. In addition, the MEP reveals that positive potential sites were around the PR molecule, whereas negative potential sites were surrounding the TPB site of atoms. The UV absorption of both arrangements is comparable to the experimental UV spectrum.

Green Alternatives in Pharmaceutical and Bioanalytical Analysis of TDM Required Drugs: Procainamide.

INTRODUCTION: In drug analysis, using non-hazardous solvents instead of the ones harmful to humans and the environment is a green strategy to protect analysts and environmental health. OBJECTIVE: Procainamide (PCA) is an antiarrhythmic drug requiring therapeutic drug monitoring (TDM) because of its narrow therapeutic window and serious side effects. AIM: The aim of this study is to develop validated green HPLC methods to be used in drug quality control and TDM analysis for PCA, thus indicating the further applicability in the analysis of TDM-required drugs, such as immunosuppressants, anti-cancer drugs, and psychiatric drugs. METHODS: Human-friendly ethanol was selected as an organic solvent in the mobile phase. PCA was eluted from NUCLEODUR 100-5 C8 ec (5 µm, 150 x 4.6 mm) column by a mobile phase containing ethanol and 50 mM NaH2PO4 buffer (5:95, v/v). The mobile phase flow rate was 1.0 ml min-1, the column temperature was 35 °C, and the wavelength at the PDA detector was 278 nm. RESULTS: Retention time for PCA was 5.0 min and 7.7 min for paracetamol as an internal standard (IS). In the green HPLC method for pharmaceutical analysis, the highest relative standard deviation (RSD) and mean recovery values were 1.32% and 98.89%, respectively. In the analysis of plasma, the sample preparation step was only smooth protein precipitation by ethanol. Thus, the bioanalytical method was fully green having a limit of detection (LOD) of 0.3 µg ml-1 and a limit of quantification (LOQ) of 0.8 µg ml-1. The therapeutic plasma concentration for PCA was reported in the range of 4-12 µg ml-1. CONCLUSION: As a result, the green HPLC methods developed and validated in this study were selective, accurate, precise, reproducible, and trustable and have the quality for the application in pharmaceutical and TDM analysis of PCA, thus encouraging green HPLC analysis of other TDM required drugs.

Inhibition of Leishmania infantum Trypanothione Reductase by New Aminopropanone Derivatives Interacting with the NADPH Binding Site.

BACKGROUND: As a result of the paucity of treatment, Leishmaniasis continues to provoke about 60,000 deaths every year worldwide. New molecules are needed, and drug discovery research is oriented toward targeting proteins crucial for parasite survival. Among them, trypanothione reductase (TR) is of remarkable interest owing to its vital role in Leishmania species protozoan parasite life. Our previously identified compound 1 is a novel chemotype endowed with a unique mode of TR inhibition thanks to its binding to a formerly unknown but druggable site at the entrance of the NADPH binding cavity, absent in human glutathione reductase (hGR). METHODS: We designed and synthesized new 3-amino-1-arylpropan-1-one derivatives structurally related to compound 1 and evaluated their potential inhibition activity on TR from Leishmania infantum (LiTR). Cluster docking was performed to assess the binding poses of the compounds. RESULTS: The newly synthesized compounds were screened at a concentration of 100 µM in in vitro assays and all of them proved to be active with residual activity percentages lower than 75%. CONCLUSIONS: Compounds 2a and 2b were the most potent inhibitors found, suggesting that an additional aromatic ring might be promising for enzymatic inhibition. Further structure-activity relationships are needed to optimize our compounds activity.

Procainamide pharmacokinetics during extracorporeal membrane oxygenation.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

Molecular basis of the different effects of procainamide and N-acetylprocainamide on the maximum upstroke velocity and half-decay time of the cardiac action potential in guinea pig papillary muscle

Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA antiarrhythmic, it has been reported that NAPA is a pure class III antiarrhythmic that affects only the repolarizing phase of the cardiac action potential. This last concept, observed exclusively in dogs, gained wide acceptance, appearing in classic pharmacology textbooks. However, evidence in species such as mice and rats indicates that NAPA can affect cardiac Na+ channels, which is unexpected for a pure class III antiarrhythmic drug. To further clarify this issue, the effects of PA (used as a reference drug) and NAPA on the maximum upstroke velocity (Vmax) and half-decay time (HDT) of the cardiac action potential were examined in the isolated right papillaris magnus of the guinea pig heart. Both PA and NAPA affected Vmax at lower concentrations than required to affect HDT, and NAPA had weaker effects on both variables. Thus, NAPA displayed typical class IA antiarrhythmic behavior. Therefore, the concept that NAPA is a pure class III antiarrhythmic drug is more species-dependent than previously envisioned. In addition, we demonstrated that the differential pharmacology of PA and NAPA is explainable, in molecular terms, by steric hindrance of the effects of NAPA and the greater number of potent aromatic-aromatic and cation π interactions with Na+ or K+ cardiac channels for PA.

Workup for Suspected Brugada Syndrome: Two Case Reports for the General Practitioner.

While a large proportion of ST-segment elevation on EKG is related to myocardial ischemia, the differential diagnosis must include pericarditis, channelopathies, and various genetic conditions. Identifying and working up such abnormalities present a challenge to primary care providers (PCPs). We present two clinical cases of young male patients with ST-segment elevation in anteroseptal leads suspicious for Brugada syndrome and show how to risk stratify and manage them. Our first case presents a 23-year-old male with no past medical history with acute onset substernal chest pain, shortness of breath, and palpitations. Initial workup revealed negative serial troponins and normal B-type natriuretic peptide (BNP). The EKG revealed ST elevation in lead V2. An evaluation for Brugada syndrome was pursued. Upon completion of a procainamide challenge, it was determined that he did not have Brugada syndrome and was shortly discharged. Our second case presents a 33-year-old male with no pertinent cardiac medical history who presented to an outpatient cardiology clinic after discovering an incidental ST elevation in V2 on EKG. His family history was negative for early atherosclerotic cardiovascular events or sudden cardiac death. The patient's initial workup was negative. Suspicion for Brugada syndrome leads to performing a procainamide challenge, which was significant for ST changes in the anterolateral leads. He was asymptomatic during the challenge and initial presentation, and no further intervention was indicated. He was advised to avoid sodium channel blocking medications and treat any fevers and was sent for genetic testing. These cases illustrate the importance of maintaining an appropriate suspicion for Brugada syndrome in young patients with minimal ischemic risk factors. We discuss a guideline-directed algorithmic workup for PCPs in suspicious individuals. Stratifying patients based on the presence of symptoms, history of tachyarrhythmias, and EKG findings before and after drug challenge allows physicians to guide further management of these patients.

Procainamide for shockable rhythm cardiac arrest in the Resuscitation Outcome Consortium.

BACKGROUND: With recent negative studies of amiodarone and lidocaine for cardiac arrest, research into other antiarrhythmics is warranted. Literature on procainamide in cardiac arrest is limited. We evaluated procainamide for out-of-hospital cardiac arrests (OHCA) from the Resuscitation Outcomes Consortium (ROC). METHODS: We included all ROC Epistry 3 OHCAs with an initial shockable rhythm that received an antiarrhythmic. We stratified cases by antiarrhythmic: procainamide, amiodarone, or lidocaine. The outcomes were prehospital return of spontaneous circulation (ROSC), ROSC in the ED, and survival to hospital discharge. We defined propensity scores based on possible confounders utilizing 1:1 propensity score matching to compare procainamide to amiodarone and lidocaine. We analyzed the matched data using logistic regression. We also used multivariable logistic regression to evaluate the association between antiarrhythmic and outcomes. RESULTS: 3087 subjects met inclusion criteria; 51 patients received only procainamide, 1776 received amiodarone, and 1418 received lidocaine. On propensity score analysis and compared to procainamide, amiodarone had similar prehospital ROSC (OR 0.7, 95% CI 0.3-1.8), ED ROSC (OR 0.6, 95% CI 0.3-1.3), and survival (OR 1.0, 95% CI 0.3-3.1). Lidocaine also had a similar prehospital ROSC (OR 0.9, 95% CI 0.4-2.2), ED ROSC (OR 1.2, 95% CI 0.5-2.7), and survival (OR 1.4, 95% CI 0.5-4.0). However, using multivariable regression, amiodarone had lower prehospital ROSC than procainamide (aOR 0.3, 95% CI 0.1-0.6). CONCLUSIONS: While associated with increased prehospital ROSC when compared with amiodarone using multivariable regression, procainamide otherwise had similar prehospital ROSC, ED ROSC, and survival. The role of procainamide in OHCA remains unclear.

Comparison of denaturing agent effects in enzymatic N-glycan release for human plasma N-glycan analysis.

Glycosylation is an essential posttranslational modification observed in the living proteome. Glycosylation profiles in glycoproteins can change in commonly observed diseases such as cancer. Identifying these changes is crucial in discovering new biomarkers for the early diagnosis of cancer. One of the main steps of N-glycan analysis is to release N-glycans from glycoproteins by specific enzymes. The study compares common denaturing agent combinations used in N-glycan release methods. In the study, human plasma was used to test the release methods of N-glycans containing different detergent combinations. The released N-glycans were labeled with the procainamide tag, purified using cellulose-containing solid-phase extraction cartridges, and analyzed by high-performance liquid chromatography-hydrophilic interaction liquid chromatography equipped with fluorescence detection (HPLC-HILIC-FLD). The results showed that the sodium dodecyl sulfate and sodium deoxycholate (SDS + SDC) detergent combination provided the highest average FLD signal areas and intensities in the N-glycan analysis. The protocol with SDS resulted in more reproducible average FLD signal areas and intensities. It was also found that the average signal FLD signal areas and intensities of the detected N-glycans were reduced when SDS and SDC were used with 1,4-dithiothreitol (DTT) reducing agents. In addition, deglycosylation of glycoproteins with various denaturing agents resulted in relatively minor variation in human plasma N-glycosylation profiles.

Ventricular fibrillation arrest due to Brugada syndrome in a coronavirus disease 2019 patient with negative procainamide challenge: a case report.

BACKGROUND: Pharmacologic challenge test is often used to diagnose Brugada syndrome (BrS) when spontaneous electrocardiograms (ECG) do not show type I Brugada pattern but reported sensitivity varies. The role of the exercise stress test in diagnosing Brugada syndrome is not well-established. CASE SUMMARY: A patient had a type I Brugada pattern ECG during the recovery phase of exercise stress test but had a negative procainamide challenge test. He had a loop recorder implanted and later survived a ventricular fibrillation (VF) arrest provoked by coronavirus disease 2019 (COVID-19). Electrocardiogram on arrival showed type 1 Brugada pattern. He was discharged after implantable cardioverter-defibrillator implantation. He later underwent genetic testing and was found to be heterozygous for c.844C>G (p.Arg282Gly) mutation in the SCN5A gene. DISCUSSION: Type 1 Brugada pattern ECG may be unmasked by ST-segment augmentation during recovery from exercise. Exercise stress test may play a role in the diagnosis of Brugada syndrome when suspicion for Brugada syndrome remains after a negative procainamide challenge test or if the patient has exercise-related symptoms. COVID-19 can unmask BrS and trigger a VF cardiac arrest.

The clinical utility of procainamide-induced late potentials on the signal averaged ECG.

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.

Effects of 1α,25-Dihydroxyvitamin D3 on the Pharmacokinetics of Procainamide and Its Metabolite N-Acetylprocainamide, Organic Cation Transporter Substrates, in Rats with PBPK Modeling Approach.

In this study, possible changes in the expression of rat organic cationic transporters (rOCTs) and rat multidrug and toxin extrusion proteins (rMATEs) following treatment with 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) were investigated. Rats received intraperitoneal administrations of 1,25(OH)2D3 for four consecutive days, and the tissues of interest were collected. The mRNA expression of rOCT1 in the kidneys was significantly increased in 1,25(OH)2D3-treated rats compared with the control rats, while the mRNA expressions of rOCT2 and rMATE1 in the kidneys, rOCT1 and N-acetyltransferase-II (NAT-II) in the liver, and rOCT3 in the heart were significantly decreased. Changes in the protein expression of hepatic rOCT1 and renal rOCT2 and rMATE1 were confirmed by western blot analysis. We further evaluated the pharmacokinetics of procainamide (PA) hydrochloride and its major metabolite N-acetyl procainamide (NAPA) in the presence of 1,25(OH)2D3. When PA hydrochloride was administered intravenously at a dose 10 mg/kg to 1,25(OH)2D3-treated rats, a significant decrease in renal and/or non-renal clearance of PA and NAPA was observed. A physiological model for the pharmacokinetics of PA and NAPA in rats was useful for linking changes in the transcriptional and translational expressions of rOCTs and rMATE1 transporters to the altered pharmacokinetics of the drugs.