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[PMID]:29215340
[Au] Autor:Yakut K; Erdogan I; Varan B; Atar I
[Ad] Endereço:Department of Pediatric Cardiology, Baskent University Ankara Hospital, Ankara, Turkey.
[Ti] Título:A Report of Brugada Syndrome Presenting with Cardiac Arrest Triggered by Verapamil Intoxication.
[So] Source:Balkan Med J;34(6):576-579, 2017 12 01.
[Is] ISSN:2146-3131
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Brugada syndrome is a disease characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death. We present this case with the updated literature to emphasise the need to consider the diagnosis of Brugada syndrome in patients admitted to the emergency ward with sudden cardiac arrest. CASE REPORT: A 16-year-old female patient was admitted to the emergency ward with complaints of weakness and abdominal pain, and she had four cardiac arrests during her evaluation period. She was referred to our clinic for permanent pacemaker implantation. She was on a temporary pace maker after having had C-reactive protein. Her physical exam was normal except for bilaterally decreased lung sounds. Lung x-ray and computed tomography, which were performed by another institution, revealed minimal pleural effusion and nothing else of significance. Blood and peritoneal fluid samples were sterile. Echocardiographic exam and cardiac enzymes were also in the normal ranges. Electrocardiographic showed incomplete right branch block in leads V1 and V2. An ajmaline test revealed specific electrocardiographic findings of the type I Brugada pattern. We proposed implanting an implantable cardioverter defibrillator to the patient as there were positive findings on the ajmaline test as well as a history of sudden cardiac arrest. After this treatment proposal, the patient's family admitted that she had taken a high dose of verapamil and thus, the encountered bradycardia was associated with verapamil overuse. The ajmaline test was repeated as it was contemplated that the previous positive ajmaline test had been associated with verapamil overuse. Implantable cardioverter defibrillator implantation was proposed again as there was a history of sudden cardiac arrest; however, the family did not consent to implantable cardioverter defibrillator, and the patient was discharged and followed up. CONCLUSION: Brugada syndrome should be considered for patients who are admitted to the emergency ward with sudden cardiac arrest though surface electrocardiographic is normal. If there is a suspicion of Brugada syndrome, repeated electrocardiographic should be performed on different occasions. Diagnosis can be clarified by upper costal electrocardiographic or by administering Na channel blockers during electrocardiographic performance.
[Mh] Termos MeSH primário: Antiarrítmicos/envenenamento
Síndrome de Brugada/induzido quimicamente
Parada Cardíaca/induzido quimicamente
Verapamil/envenenamento
[Mh] Termos MeSH secundário: Adolescente
Ajmalina/farmacologia
Síndrome de Brugada/diagnóstico
Síndrome de Brugada/fisiopatologia
Diagnóstico Diferencial
Eletrocardiografia
Feminino
Testes Genéticos
Parada Cardíaca/fisiopatologia
Seres Humanos
Fatores Desencadeantes
Bloqueadores dos Canais de Sódio/administração & dosagem
Tentativa de Suicídio
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Sodium Channel Blockers); 1PON08459R (Ajmaline); CJ0O37KU29 (Verapamil)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.4274/balkanmedj.2016.1301


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[PMID]:29038102
[Au] Autor:Leong KMW; Ng FS; Yao C; Roney C; Taraborrelli P; Linton NWF; Whinnett ZI; Lefroy DC; Davies DW; Boon Lim P; Harding SE; Peters NS; Kanagaratnam P; Varnava AM
[Ad] Endereço:From the National Heart and Lung Institute, Imperial College London, United Kingdom (K.M.W.L., F.S.N., C.R., N.W.F.L., Z.I.W., P.B.L., S.E.H., N.S.P., P.K.); Imperial College Healthcare NHS Trust, London, United Kingdom (K.M.W.L., F.S.N., P.T., N.W.F.L., Z.I.W., D.C.L., D.W.D., P.B.L., N.S.P., P.K.,
[Ti] Título:ST-Elevation Magnitude Correlates With Right Ventricular Outflow Tract Conduction Delay in Type I Brugada ECG.
[So] Source:Circ Arrhythm Electrophysiol;10(10), 2017 Oct.
[Is] ISSN:1941-3084
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The substrate location and underlying electrophysiological mechanisms that contribute to the characteristic ECG pattern of Brugada syndrome (BrS) are still debated. Using noninvasive electrocardiographical imaging, we studied whole heart conduction and repolarization patterns during ajmaline challenge in BrS individuals. METHODS AND RESULTS: A total of 13 participants (mean age, 44±12 years; 8 men), 11 concealed patients with type I BrS and 2 healthy controls, underwent an ajmaline infusion with electrocardiographical imaging and ECG recordings. Electrocardiographical imaging activation recovery intervals and activation timings across the right ventricle (RV) body, outflow tract (RVOT), and left ventricle were calculated and analyzed at baseline and when type I BrS pattern manifested after ajmaline infusion. Peak J-ST point elevation was calculated from the surface ECG and compared with the electrocardiographical imaging-derived parameters at the same time point. After ajmaline infusion, the RVOT had the greatest increase in conduction delay (5.4±2.8 versus 2.0±2.8 versus 1.1±1.6 ms; =0.007) and activation recovery intervals prolongation (69±32 versus 39±29 versus 21±12 ms; =0.0005) compared with RV or left ventricle. In controls, there was minimal change in J-ST point elevation, conduction delay, or activation recovery intervals at all sites with ajmaline. In patients with BrS, conduction delay in RVOT, but not RV or left ventricle, correlated to the degree of J-ST point elevation (Pearson , 0.81; <0.001). No correlation was found between J-ST point elevation and activation recovery intervals prolongation in the RVOT, RV, or left ventricle. CONCLUSIONS: Magnitude of ST (J point) elevation in the type I BrS pattern is attributed to degree of conduction delay in the RVOT and not prolongation in repolarization time.
[Mh] Termos MeSH primário: Potenciais de Ação
Mapeamento Potencial de Superfície Corporal
Síndrome de Brugada/diagnóstico
Eletrocardiografia
Sistema de Condução Cardíaco/fisiopatologia
Frequência Cardíaca
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Adulto
Ajmalina/administração & dosagem
Antiarrítmicos/administração & dosagem
Síndrome de Brugada/fisiopatologia
Estudos de Casos e Controles
Feminino
Sistema de Condução Cardíaco/efeitos dos fármacos
Frequência Cardíaca/efeitos dos fármacos
Seres Humanos
Masculino
Meia-Idade
Valor Preditivo dos Testes
Período Refratário Eletrofisiológico
Processamento de Sinais Assistido por Computador
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 1PON08459R (Ajmaline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE


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[PMID]:28500178
[Au] Autor:Pappone C; Brugada J; Vicedomini G; Ciconte G; Manguso F; Saviano M; Vitale R; Cuko A; Giannelli L; Calovic Z; Conti M; Pozzi P; Natalizia A; Crisà S; Borrelli V; Brugada R; Sarquella-Brugada G; Guazzi M; Frigiola A; Menicanti L; Santinelli V
[Ad] Endereço:From the Arrhythmology Department (C.P., G.V., G.C., F.M., M.S., R.V., A.C., L.G., Z.C., M.C., A.N., S.C., V.B., V.S.) and Cardiac Surgery Department (A.F., L.M.), IRCCS Policlinico San Donato, San Donato Milanese, Italy; Cardiology Department, Cardiovascular Institute, Hospital Clinic and IDIBAPS,
[Ti] Título:Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome.
[So] Source:Circ Arrhythm Electrophysiol;10(5):e005053, 2017 May.
[Is] ISSN:1941-3084
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome. METHODS AND RESULTS: A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right ventricle epicardium, which were wider in group 1 ( =0.007). AES increased after ajmaline in both groups ( <0.001) and was larger in men ( =0.008). The increase of type-1 ST-segment elevation correlated with AES expansion ( =0.682, <0.001). Radiofrequency ablation eliminated AES leading to ECG normalization and VT/VF noninducibility in all patients. During a median follow-up of 10 months, the ECG remained normal even after ajmaline in all except 2 patients who underwent a repeated effective procedure for recurrent VF. CONCLUSIONS: In Brugada syndrome, AES is commonly located in the right ventricle epicardium and ajmaline exposes its extent and distribution, which is correlated with the degree of coved ST-elevation. AES elimination by radiofrequency ablation results in ECG normalization and VT/VF noninducibility. Substrate-based ablation is effective in potentially eliminating the arrhythmic consequences of this genetic disease. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02641431.
[Mh] Termos MeSH primário: Síndrome de Brugada/cirurgia
Ablação por Cateter
Taquicardia Ventricular/prevenção & controle
Fibrilação Ventricular/prevenção & controle
[Mh] Termos MeSH secundário: Potenciais de Ação
Adolescente
Adulto
Idoso
Ajmalina/administração & dosagem
Antiarrítmicos/administração & dosagem
Síndrome de Brugada/complicações
Síndrome de Brugada/diagnóstico
Síndrome de Brugada/fisiopatologia
Morte Súbita Cardíaca/etiologia
Morte Súbita Cardíaca/prevenção & controle
Desfibriladores Implantáveis
Cardioversão Elétrica/instrumentação
Eletrocardiografia
Técnicas Eletrofisiológicas Cardíacas
Feminino
Frequência Cardíaca
Seres Humanos
Masculino
Meia-Idade
Valor Preditivo dos Testes
Estudos Prospectivos
Taquicardia Ventricular/diagnóstico
Taquicardia Ventricular/etiologia
Taquicardia Ventricular/fisiopatologia
Resultado do Tratamento
Fibrilação Ventricular/diagnóstico
Fibrilação Ventricular/etiologia
Fibrilação Ventricular/fisiopatologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 1PON08459R (Ajmaline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170514
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCEP.117.005053


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[PMID]:27829006
[Au] Autor:El-Battrawy I; Lang S; Zhao Z; Akin I; Yücel G; Meister S; Patocskai B; Behnes M; Rudic B; Tülümen E; Liebe V; Tiburcy M; Dworacek J; Zimmermann WH; Utikal J; Wieland T; Borggrefe M; Zhou XB
[Ad] Endereço:First Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
[Ti] Título:Hyperthermia Influences the Effects of Sodium Channel Blocking Drugs in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
[So] Source:PLoS One;11(11):e0166143, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Fever can increase the susceptibility to supraventricular and ventricular arrhythmias, in which sodium channel dysfunction has been implicated. Whether fever influences the efficacy of sodium channel blocking drugs is unknown. The current study was designed to investigate the temperature dependent effects of distinct sodium channel blocking drugs on the sodium currents in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). METHODS AND RESULTS: hiPSC-CMs were generated from human skin fibroblasts of a healthy donor. The peak and late sodium currents (INa), steady-state activation, inactivation and recovery from inactivation of INa in hiPSC-CMs were analyzed using the whole-cell patch clamp technique. The effects of different concentrations of the antiarrhythmic drugs flecainide, lidocaine, ajmaline and the antianginal drug ranolazine on INa were tested at 36°C and 40°C. Increasing the temperature of the bath solution from 36°C to 40°C enhanced the inhibition of peak INa but reduced the inhibition of late INa by flecainide and lidocaine. By contrast, increasing the temperature reduced the effect of ajmaline and ranolazine on the peak INa but not late INa. None of the tested drugs showed temperature-dependent effects on the steady-state activation and inactivation as well as on the recovery from inactivation of INa in hiPSC-CMs. CONCLUSIONS: Temperature variation from the physiological to the febrile range apparently influences the effects of sodium channel blockers on the sodium currents. This may influence their antiarrhythmic efficacy in patients suffering from fever.
[Mh] Termos MeSH primário: Temperatura Alta/efeitos adversos
Miócitos Cardíacos/efeitos dos fármacos
Células-Tronco Pluripotentes/efeitos dos fármacos
Bloqueadores dos Canais de Sódio/farmacologia
Canais de Sódio/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ajmalina/farmacologia
Flecainida/farmacologia
Seres Humanos
Lidocaína/farmacologia
Técnicas de Patch-Clamp
Reação em Cadeia da Polimerase
Ranolazina/farmacologia
Canais de Sódio/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sodium Channel Blockers); 0 (Sodium Channels); 1PON08459R (Ajmaline); 98PI200987 (Lidocaine); A6IEZ5M406 (Ranolazine); K94FTS1806 (Flecainide)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161110
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0166143


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[PMID]:27255966
[Au] Autor:Mellor G; Nelson CP; Robb C; Raju H; Wijeyeratne Y; Hengstenberg C; Reinhard W; Papadakis M; Sharma S; Samani NJ; Behr ER
[Ad] Endereço:From the Cardiac Research Centre, St. George's University of London, London, United Kingdom (G.M., C.R., H.R., Y.W., M.P., S.S., E.R.B.); Department of Cardiovascular Sciences, University of Leicester & National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Lei
[Ti] Título:The Prevalence and Significance of the Early Repolarization Pattern in Sudden Arrhythmic Death Syndrome Families.
[So] Source:Circ Arrhythm Electrophysiol;9(6), 2016 Jun.
[Is] ISSN:1941-3084
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear. METHODS AND RESULTS: We analyzed 12-lead ECGs of 401 first-degree relatives of individuals who had died from SADS. The prevalence of ER patterns was compared with family-clustered controls. ER was more common in SADS family members than in controls (21% versus 8%; odds ratio: 5.14; 95% confidence interval, 3.37-7.84) independent of the presence of a familial cardiac diagnosis. Both ascending and horizontal ER patterns were more common. In addition, ER was investigated for associations with findings from ajmaline provocation (n=332), exercise ECG (n=304), and signal-averaged ECG (n=118) when performed. ER was associated with a trend toward late depolarization, in general was suppressed with exercise and was unaffected by ajmaline. Inferior and horizontal patterns were, however, more likely to persist during exercise. Augmentation of ER with ajmaline was rare. CONCLUSIONS: The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness. The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology. The differing response of ER subtypes to exercise and ajmaline provocation suggests underlying mechanisms of both abnormal repolarization and depolarization.
[Mh] Termos MeSH primário: Arritmias Cardíacas/genética
Arritmias Cardíacas/fisiopatologia
Morte Súbita Cardíaca
Morte Súbita
[Mh] Termos MeSH secundário: Adulto
Ajmalina
Estudos de Casos e Controles
Eletrocardiografia
Feminino
Seres Humanos
Masculino
Prevalência
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
1PON08459R (Ajmaline)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170614
[Lr] Data última revisão:
170614
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160604
[St] Status:MEDLINE


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[PMID]:27122470
[Au] Autor:Cázares-Flores P; Levac D; De Luca V
[Ad] Endereço:Department of Biological Sciences, Brock University, 1812 Sir Isaac Brock Way, St Catharines, L2S 3A1, Canada.
[Ti] Título:Rauvolfia serpentina N-methyltransferases involved in ajmaline and Nß -methylajmaline biosynthesis belong to a gene family derived from γ-tocopherol C-methyltransferase.
[So] Source:Plant J;87(4):335-42, 2016 Aug.
[Is] ISSN:1365-313X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ajmaline biosynthesis in Rauvolfia serpentina has been one of the most studied monoterpenoid indole alkaloid (MIA) pathways within the plant family Apocynaceae. Detailed molecular and biochemical information on most of the steps involved in the pathway has been generated over the last 30 years. Here we report the identification, molecular cloning and functional expression in Escherichia coli of two R. serpentinacDNAs that are part of a recently discovered γ-tocopherol-like N-methyltransferase (γ-TLMT) family and are involved in indole and side-chain N-methylation of ajmaline. Recombinant proteins showed remarkable substrate specificity for molecules with an ajmalan-type backbone and strict regiospecific N-methylation. Furthermore, N-methyltransferase gene transcripts and enzyme activity were enriched in R. serpentina roots which correlated with accumulation of ajmaline alkaloid. This study elucidates the final step in the ajmaline biosynthetic pathway and describes the enzyme responsible for the formation of Nß -methylajmaline, an unusual charged MIA found in R. serpentina.
[Mh] Termos MeSH primário: Ajmalina/biossíntese
Metiltransferases/metabolismo
Rauwolfia/enzimologia
Alcaloides de Triptamina e Secologanina/metabolismo
[Mh] Termos MeSH secundário: Ajmalina/química
Vias Biossintéticas
Clonagem Molecular
Biologia Computacional
Metiltransferases/genética
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Raízes de Plantas/química
Raízes de Plantas/enzimologia
Raízes de Plantas/genética
Rauwolfia/química
Rauwolfia/genética
Proteínas Recombinantes
Alcaloides de Triptamina e Secologanina/química
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Proteins); 0 (Recombinant Proteins); 0 (Secologanin Tryptamine Alkaloids); 1PON08459R (Ajmaline); EC 2.1.1.- (Methyltransferases); EC 2.1.1.95 (gamma-tocopherol methyltransferase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160429
[St] Status:MEDLINE
[do] DOI:10.1111/tpj.13186


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[PMID]:27032887
[Au] Autor:Bürkle G; Schäfer H; Marschall C; Brugada P; Ehrlich JR
[Ad] Endereço:Cardiology, St Josefs-Hospital, Wiesbaden, Germany.
[Ti] Título:Pharmacological Provocation of Outflow-Tract Tachycardia in a Patient With Brugada Syndrome.
[So] Source:Can J Cardiol;32(12):1577.e5-1577.e7, 2016 Dec.
[Is] ISSN:1916-7075
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We present a case of a symptomatic patient with Brugada syndrome, who had sustained right ventricular outflow tract tachycardia after pronounced exercise-induced ST segment elevation in V and V . In electrophysiological study he developed right ventricular outflow tract tachycardia provoked by combined infusion of ajmaline and orciprenaline. After ablation no further arrhythmia was provoked by pharmacological stimulation.
[Mh] Termos MeSH primário: Síndrome de Brugada
Ablação por Cateter/métodos
Taquicardia Ventricular
[Mh] Termos MeSH secundário: Ajmalina/administração & dosagem
Ajmalina/efeitos adversos
Antiarrítmicos/administração & dosagem
Antiarrítmicos/efeitos adversos
Síndrome de Brugada/diagnóstico
Síndrome de Brugada/fisiopatologia
Síndrome de Brugada/terapia
Eletrocardiografia/métodos
Sistema de Condução Cardíaco/efeitos dos fármacos
Sistema de Condução Cardíaco/fisiopatologia
Seres Humanos
Masculino
Metaproterenol/administração & dosagem
Metaproterenol/efeitos adversos
Meia-Idade
Estimulação Química
Taquicardia Ventricular/induzido quimicamente
Taquicardia Ventricular/fisiopatologia
Taquicardia Ventricular/prevenção & controle
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 1PON08459R (Ajmaline); 53QOG569E0 (Metaproterenol)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170720
[Lr] Data última revisão:
170720
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160402
[St] Status:MEDLINE


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[PMID]:26941343
[Au] Autor:Dobbels B; De Cleen D; Ector J
[Ad] Endereço:Department of Internal Medicine, University of Leuven, Leuven, Belgium bieke.dobbels@student.kuleuven.be.
[Ti] Título:Ventricular arrhythmia during ajmaline challenge for the Brugada syndrome.
[So] Source:Europace;18(10):1501-1506, 2016 Oct.
[Is] ISSN:1532-2092
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Brugada syndrome is a genetic disease characterized by an abnormal electrocardiogram (ECG) and an elevated risk of sudden cardiac death. Sodium channel blockers (SCBs), such as ajmaline, are used to unmask the characteristic type 1 Brugada electrocardiographic pattern. We review the literature on the incidence of ventricular arrhythmia (VA) during SCB challenge. We evaluate the clinical and electrocardiographic characteristics of these patients as well as their prognosis. All articles published from January 2000 until August 2015, in which the incidence and predictors of VAs during SCB challenge were reported, are reviewed. The occurrence of VA during SCB challenge ranges from 0 to 17.8%. The weighted average for induction of any VA during sodium blocking challenge is 2.4%; for non-sustained ventricular tachycardia (VT), it is 0.34% and for sustained VT 0.59%. No fatal cases were reported. Predictors may be young age, conduction disturbance at baseline ECG, and mutations in the SCN5A gene. All other clinical and electrocardiographic characteristics failed to be consistent predictors. Life-threatening arrhythmias during SCB challenge are not an exceptional event. Therefore, provocation testing must necessarily be performed in an appropriate environment in which advanced life support facilities are present. Patients who have a higher risk for induced arrhythmias might be those who display a conduction disturbance at baseline ECG or have certain SCN5A mutations or are of a younger age. However, survivors of these induced arrhythmias do not seem to suffer from a worse prognosis.
[Mh] Termos MeSH primário: Ajmalina/administração & dosagem
Síndrome de Brugada/complicações
Síndrome de Brugada/tratamento farmacológico
Taquicardia Ventricular/epidemiologia
Bloqueadores do Canal de Sódio Disparado por Voltagem/administração & dosagem
[Mh] Termos MeSH secundário: Síndrome de Brugada/genética
Morte Súbita Cardíaca
Eletrocardiografia
Seres Humanos
Incidência
Mutação
Canal de Sódio Disparado por Voltagem NAV1.5/genética
Fatores de Risco
Taquicardia Ventricular/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (NAV1.5 Voltage-Gated Sodium Channel); 0 (SCN5A protein, human); 0 (Voltage-Gated Sodium Channel Blockers); 1PON08459R (Ajmaline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160305
[St] Status:MEDLINE


  9 / 799 MEDLINE  
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[PMID]:26827883
[Au] Autor:Namjoshi OA; Cook JM
[Ad] Endereço:RTI International, Center for Drug Discovery, Research Triangle Park, NC, USA.
[Ti] Título:Sarpagine and Related Alkaloids.
[So] Source:Alkaloids Chem Biol;76:63-169, 2016.
[Is] ISSN:1099-4831
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The sarpagine-related macroline and ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the family Apocynaceae. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine-related alkaloids and the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists. A total of 115 newly isolated sarpagine-related macroline and ajmaline alkaloids, along with their physicochemical properties have been included in this chapter. A general and efficient strategy for the synthesis of these monomeric alkaloids, as well as bisindoles, has been presented, which involves application of the asymmetric Pictet-Spengler reaction (>98% ee) as a key step because of the ease of scale up of the tetracyclic template. Also included in this chapter are the syntheses of the sarpagine-related alkaloids, published since 2000.
[Mh] Termos MeSH primário: Alcaloides de Indol/metabolismo
Alcaloides de Triptamina e Secologanina/metabolismo
[Mh] Termos MeSH secundário: Ajmalina/biossíntese
Ajmalina/química
Alcaloides de Indol/química
Espectroscopia de Ressonância Magnética
Alcaloides de Triptamina e Secologanina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; REVIEW
[Nm] Nome de substância:
0 (Indole Alkaloids); 0 (Secologanin Tryptamine Alkaloids); 1PON08459R (Ajmaline); XD54MPV6VQ (sarpagine)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160202
[St] Status:MEDLINE


  10 / 799 MEDLINE  
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[PMID]:26827882
[Au] Autor:Wu F; Kercmar P; Zhang C; Stöckigt J
[Ad] Endereço:Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan, P.R. China; Department of Pharmacology, Baylor College of Medicine, Houston, TX, USA.
[Ti] Título:Sarpagan-Ajmalan-Type Indoles: Biosynthesis, Structural Biology, and Chemo-Enzymatic Significance.
[So] Source:Alkaloids Chem Biol;76:1-61, 2016.
[Is] ISSN:1099-4831
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The biosynthetic pathway of the monoterpenoid indole alkaloid ajmaline in the genus Rauvolfia, in particular Rauvolfia serpentina Benth. ex Kurz, is one of the few pathways that have been comprehensively uncovered. Every step in the progress of plant alkaloid biosynthesis research is due to the endeavors of several generations of scientists and the advancement of technologies. The tissue and cell suspension cultures developed in the 1970s by M.H. Zenk enabled the extraction of alkaloids and crude enzymes for use as experimental materials, thus establishing the foundation for further research on enzymatic reaction networks. In vivo NMR technology was first used in biosynthetic investigations in the 1990s following the invention of high-field cryo-NMR, which allowed the rapid and reliable detection of bioconversion processes within living plant cells. Shortly before, in 1988, a milestone was reached with the heterologous expression of the strictosidine synthase cDNA, which paved the way for the application of "reverse genetics" and "macromolecular crystallography." Both methods allowed the structural analysis of several Rauvolfia enzymes involved in ajmaline biosynthesis and expanded our knowledge of the enzyme mechanisms, substrate specificities, and structure-activity relationships. It also opened the door for rational enzyme engineering and metabolic steering. Today, the research focus of ajmaline biosynthesis is shifting from "delineation" to "utilization." The Pictet-Spenglerase strictosidine synthase, strictosidine glucosidase, together with raucaffricine glucosidase, as pioneers in this area, have become useful tools to generate "privileged structures" and "diversity oriented" syntheses, which may help to construct novel scaffolds and to set up libraries of sarpagan-ajmalan-type alkaloids in chemo-enzymatic approaches.
[Mh] Termos MeSH primário: Ajmalina/biossíntese
Alcaloides de Indol/metabolismo
[Mh] Termos MeSH secundário: Ajmalina/química
Glucosidases/metabolismo
Alcaloides de Indol/química
Espectroscopia de Ressonância Magnética
Alcaloides de Triptamina e Secologanina/química
Alcaloides de Triptamina e Secologanina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Indole Alkaloids); 0 (Secologanin Tryptamine Alkaloids); 1PON08459R (Ajmaline); EC 3.2.1.- (Glucosidases); XD54MPV6VQ (sarpagine)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160201
[Lr] Data última revisão:
160201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160202
[St] Status:MEDLINE



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