Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

Fibrilación auricular en el primer nivel de atención médica / Atrial fibrillation in the first level of medical care

Introducción: La fibrilación auricular constituye un importante problema de salud, debido al aumento de su incidencia con la edad y a la asociación con otras morbilidades. Los pacientes con fibrilación auricular tienen de 4 a 5 veces mayor riesgo de accidente cerebrovascular y alrededor del doble de riesgo de mortalidad en relación con los que no sufren fibrilación auricular. Objetivo: Caracterizar a los pacientes con fibrilación auricular atendidos en el Policlínico de Guanabo. Métodos: Se realizó un estudio retrospectivo descriptivo transversal que incluyó a todos los pacientes adultos ingresados con esta arritmia en el Área Intensiva Municipal Guanabo. Se revisaron 24 meses (10 de 2017 y 2018 y primer cuatrimestre de 2019). Las variables estudiadas fueron: diagnóstico principal al ingreso, estado hemodinámico, letalidad, estrategia terapéutica y conducta final. Resultados: Al ingreso el diagnóstico principal fue fibrilación auricular (52 por ciento), además de presentar otra afección asociada. El resto de los pacientes (44) tuvo otros diagnósticos; 6,5 por ciento llegó con inestabilidad hemodinámica. Fallecieron dos casos para una letalidad de 2,2 por ciento. La cardioversión farmacológica fue usada en 68 casos (75 por ciento. Los medicamentos más usados fueron amiodarona, atenolol y digoxina. La cardioversión eléctrica se aplicó solo en cuatro casos de los seis inestables. El 58 por ciento egresó a domicilio, remitió 39 por ciento, 70 por ciento tuvo una estadía entre dos y tres horas. Conclusiones: El diagnóstico principal al ingreso correspondió a la fibrilación auricular, con estabilidad hemodinámica y letalidad baja. La estrategia terapéutica utilizada fue amiodarona, atenolol y digoxina. El servicio logra alta resolutividad. La estadía promedio fue dos a tres horas(AU)

Introduction: Atrial fibrillation is an important health concerns, due to its increasing incidence with aging and association with other diseases. Patients with atrial fibrillation have 4-5 times the risk of stroke and about twice the risk of death in relation to those without atrial fibrillation. Objective: To characterize patients with atrial fibrillation treated at Guanabo outpatient Polyclinic. Methods: A retrospective, descriptive and cross-sectional study was carried out with all the patients admitted, with the aforementioned arrhythmia, in the municipal intensive care unit of Guanabo (eastern Havana, Cuba). Twenty-four months were reviewed (10 from 2017 and 2018, and the first four-month period of 2019). The variables studied were main diagnosis at admission, hemodynamic status, lethality, therapeutic strategy, and final behavior. Results: Regarding their main diagnosis on admission, fibrillation accounted for 52 percent of cases, another entity plus electrocardiographic findings accounted for the rest; 6.5 percent arrived with hemodynamic instability. Two cases died, which resulted in a case fatality rate of 2.2 percent. Pharmacological cardioversion was used in 68 cases (75 percent). The most commonly used drugs were amiodarone, atenolol and digoxin. Electrical cardioversion was applied in only four of the six unstable cases. Fifty-eight percent were discharged home, 39 percent were remitted, and 70 percent had a stay between two and three hours. Conclusions: The main diagnosis at admission was atrial fibrillation, with hemodynamic stability and low lethality. The therapeutic strategy consisted of amiodarone, atenolol and digoxin. The service showed high solving capacity. The average length of stay was two to three hours(AU)

Statistical analysis of medication information labeling of pregnant women and lactating women in the instructions of antiarrhythmic drugs / 中国药房

OBJECTIVE To provide reference for standardizing the labeling of medication information for pregnant women and lactating women in the instructions of antiarrhythmic drugs. METHODS The instructions of antiarrhythmic drugs were collected from the terms of “medication reference ”on official website of Yimaitong Technology Co. ，Ltd. The labeling of medication information of pregnant women and lactating women were sorted out ，counted and analyzed with reference to the Detailed Rules for Specifications of Instructions of Chemical Drugs and Therapeutic Biological Products issued by the State Food and Drug Administration. RESULTS A total of 111 instructions of antiarrhythmic drugs were collected in this study ，of which 102 instructions were marked with “medication for pregnant women ”（91.89％），of which the proportion of those with medication guidance and without medication guidance were 75.68％ and 16.22％ respectively. Eighty-eight drug instructions were marked with the item “medication for lactating women ”（79.28％），of which the proportion of those with medication guidance and without medication guidance were 70.27％ and 9.01％ respectively. Among different categories of antiarrhythmic drugs ，the best labeling of “medication for pregnant women ”was class Ⅰ antiarrhythmic drugs （100％），while class Ⅲ drugs（25.00％）were most missing ； class Ⅳ antiarrhythmic drugs （94.44％）were the best labeled for “medication for lactating women ”，while class Ⅰ（26.47％）were the most missing . There were differences in the labeling contents of “medication for pregnant women ”and“medication for lactating women ”in some drug instructions of the same variety from different manufacturers. Among the 99 drug instructions of domestic pharmaceutical enterprises ， 92 listed the items of “medication for pregnant women”and“medication for lactating women ”，and the proportions of them with medication guidance were 74.75％ and 69.70％ respectively；among the 12 drug instructions of foreign pharmaceutical enterprises ，10（83.33％）listed the items of “medication for pregnant women ”and“medication for lactating women ”，and the proportion with medication guidance was 83.33％ and 75.00％ respectively. CONCLUSIONS There are some problems in the labeling content of domestic antiarrhythmic drug instructions，such as the lack of information related to “medication for pregnant women ”and“medication for lactating women ”， the confusion of guidance expression ， the inconsistent content of drug instructions of the same variety from different manufacturers，the lag of modification and update ，and the poor standardization of drug instructions. Drug supervision and administration departments and drug manufacturers should pay attention to them and constantly strengthen the management and standardization of instructions.

Prescription profile of antiarrhythmic drugs in a group of patients in Colombia / Perfil de prescripción de fármacos antiarrítmicos en un grupo de pacientes en Colombia

Abstract Objective: To determine the prescription patterns of antiarrhythmic drugs and variables associated with their use in a population of patients affiliated with the Colombian Health System. Methods: A cross-sectional study was performed on a population database with patients who received antiarrhythmics from March to May 2016. Sociodemographic, pharmacological and comedication variables were included. SPSS-24 was used for data analysis using X2 tests and multivariate analyses. Results: In total, 2772 patients were treated with antiarrhythmics in the evaluated period. The mean age was 70.1 ± 13.1 years, and 51.2% were women. In total, 79.4% used a β-blocker, 58.5% amiodarone and 2.9% a calcium channel blocker. Moreover, 1192 (43.0%) patients were prescribed a single antiarrhythmic, and 1580 (57.0%) received two or more. There were 2603 patients (93.9%) with comedication, including lipid-lowering drugs (62.6%), inhibitors of the renin angiotensin aldosterone system (62.6%) and antiplatelet drugs (42.0%). Age older than 65 years increased the probability of comedication (odds ratio [OR]: 2.48; 95% confidence interval [95% CI]: 1.59-3.85), and the risk was proportional to age. We identified 1364 patients treated with conditional risk medications for QT prolongation (49.2%), 68 with a possible risk (2.5%) and 171 (6.2%) with a known risk. Conclusion: Antiarrhythmic drugs recommended by clinical practice guidelines are mainly used; however, risk interactions interactions of QT prolongation were identified and should be taken into account by physicians to avoid adverse events or complications.

Resumen Objetivo: determinar los patrones de prescripción de fármacos antiarrítmicos y variables asociadas a su utilización en una población de pacientes afiliados al sistema de salud de Colombia. Métodos: estudio de corte transversal sobre una base de datos poblacional con pacientes que recibieron antiarrítmicos entre marzo y mayo de 2016. Se incluyeron variables sociodemográficas, farmacológicas y de comedicación. Para el análisis de datos se utilizó SPSS-24, realizando pruebas X2 y análisis multivariado. Resultados: se encontraron 2 772 pacientes en tratamiento con antiarrítmicos en el periodo evaluado, la edad promedio fue 70,1 ± 13,1 años, 51,2 % eran mujeres. El 79,4% utilizó algún β-bloqueador, 58,5% amiodarona y 2,9 % algún bloqueante de canales de calcio. Al 43 % se les prescribió un solo antiarrítmico y 57 % recibieron dos o más. El 93,9 % tenía con alguna comedicación, especialmente hipolipemiantes (62,6 %), inhibidores del sistema renina angiotensina aldosterona (62,6 %) y antiagregantes (42 %). Ser mayor de 65 años aumentó la probabilidad de comedicación (OR:2,48; IC95 %:1,59-3,85) y el riesgo fue proporcional al incremento de la edad. El 49,2 % (n=1364) estaban tratados con medicamentos de riesgo condicional de prolongación del QT, 2,5 % (n=68) con riesgo posible y 6,2% (n=171) de riesgo conocido. Conclusión: se están utilizando los mismos fármacos recomendados por las guías de práctica clínica; sin embargo, se encontraron interacciones de riesgo de prolongación del intervalo QT que deben ser tenidas en cuenta para evitar eventos o complicaciones en los pacientes.

Current status of the clinical practice and analysis on the ratioanl prescription of antiarrhythmic drugs in Chinese patients with atrial fibrillation: Results from the Chinese Atrial Fibrillation Registry (CAFR) trial / 中华心血管病杂志

Objective: To explore the practice patterns and the related factors of oral antiarrhythmic drug (AAD) treatment in Chinese patients with atrial fibrillation (AF), and to evaluate the compliance of AAD application to atrial fibrillation management guidelines. Methods: From August 2011 to August 2016, medical records from 18 014 patients with AF were analyzed based on data from the Chinese Atrial Fibrillation Registry trial. Patients were divided into AAD group (7 788 cases, 43.23%) and non-AAD group (10 226 cases, 56.77%) according to whether AAD was used at baseline or at the time of first use during follow-up. Amiodarone (4 129 cases, 53.02%) and propafenone (3 211 cases, 41.23%) were the mostly prescribed AAD and subgroup analysis was performed accordingly. Medical records were analyzed by random forest regression to evaluate the use of AAD and related factors in patients with AF, and the rationality of AAD was analyzed according to the guidelines for the management of atrial fibrillation. Result: A total of 18 014 patients were included in this study, of which 60.48% (10 895/18 014) were male patients, 22.65% (4 081/18 014) were elderly patients(≥75 years old), there were 7 788 patients (43.23%) in AAD group, and 10 226 patients(56.77%) in non-AAD group. Compared with the non-AAD group, the elderly patients (≥75 years old, 13.74%(1 070/7 788) vs. 29.44%(3 011/10 226)), persistent AF (28.95% (2 250/7 788) 45.80% (4 683/10 226)), heart failure(8.29% (646/7 788) vs. 21.95% (2 245/10 226)), stroke and (or) TIA(12.15% (946/7 788) vs. 19.95% (2 040/10 226)), renal dysfunction(16.36%(1 274/7 788) vs. 29.37% (3 003/10 226)), and high thromboembolism risk(60.17% (4 748/7 788) vs. 76.40% (7 813/10 226)) were less prevalent in the AAD subgroup (P<0.001). Multivariate analysis showed that patients in tertiary hospitals (OR=3.72, 95%CI 3.17-4.37) were more likely to use AAD, elderly patients (≥75 years old, OR=0.47, 95%CI 0.39-0.55), persistent atrial fibrillation (OR=0.66, 95%CI 0.60-0.72), and patients with heart failure (OR=0.54, 95%CI 0.47-0.63), stroke and (or) TIA (OR=0.77, 95%CI 0.68-0.87), renal dysfunction (OR=0.75, 95%CI 0.59-0.95) and high thromboembolism risk(OR=0.7, 95%CI 0.58-0.84) were more likely not to use AAD(P<0.05). In the AAD group, amiodarone and propafenone were the most commonly used AAD, accounting for 53.02% (4 129/7 788) and 41.23% (3 211/7 788), respectively. Multivariate analysis showed that patients with persistent atrial fibrillation (OR=4.57, 95%CI 3.94-5.29) and coronary heart disease (OR=4.14, 95%CI 3.03-5.64), heart failure (OR=2.07, 95%CI 1.48-2.89), non-ischemic cardiomyopathy (OR=4.84, 95%CI 2.41-9.73) were more likely to use amiodarone, and those with normal left ventricular ejection fraction (OR=0.31, 95%CI 0.15-0.65) and low thromboembolism risk (OR=0.78, 95%CI 0.63-0.97) were more likely to use propafenone (P<0.001). The overall incidence of AAD treatment, which was not indicated by the guidelines was 6.5% (480/7 340); 5.1% (212/4 129) in the amiodarone group and 8.3% (268/3 211) in the propafenone group, respectively. Compared with the rational AAD use group, the proportion of irrational drug use was higher in the elderly (≥75 years old) (20.4% (98/480) vs. 12.9% (887/6 860)), patients of high thromboembolism risk (77.1% (379/480) vs. 59.0% (4 047/6 860)), and in non-tertiary hospitals (7.1% (34/480) vs. 3.3% (299/6 860)), but lower in men(50.8% (244/480) vs. 64.5% (4 427/6 860)), P<0.001. Conclusions: The patients with paroxysmal atrial fibrillation, who were treated with AAD, were mostly patients with fewer complications, and the patients who were treated with amiodarone were mostly patients with persistent atrial fibrillation, patients were more likely to complicate with organic heart disease. The incidence of AAD that do not comply with the guidelines was low, and it was more common in non-tertiary hospitals and the elder patients with high thromboembolism risk.

Evaluación diagnóstica y manejo terapéutico farmacológico en pacientes con fibrilación auricular / Diagnostic evaluation and pharmacological therapeutic management in patients with atrial fibrillation

La fibrilación auricular (FA) es la arritmia sostenida más frecuente que puede presentarse en una amplia variedad de condiciones clínicas. A pesar de los progresos en el tratamiento de los pacientes con FA, esta arritmia sigue siendo una de las más importantes causas de accidente cerebrovascular, insuficiencia cardiaca, muerte súbita y morbilidad cardiovascular en todo el mundo. El objetivo del tratamiento con fármacos antiarrítmicos es mejorar los síntomas relacionados con la FA, y buscar un equilibrio entre la carga sintomática, la posibilidad de reacciones farmacológicas adversas y las preferencias del paciente. El control de la frecuencia cardiaca a corto y largo plazo se puede lograr con bloqueadores beta, digoxina, bloqueadores de los canales del calcio o tratamiento combinado. Si bien otros fármacos antiarrítmicos de clase III también tienen un efecto limitador de la frecuencia, solo deben emplearse para el control del ritmo cardiaco. Restaurar y mantener el ritmo sinusal también es una parte integral del tratamiento de la FA. Los fármacos antiarrítmicos de clase III duplican la tasa de pacientes en ritmo sinusal. El tratamiento para el control del ritmo está indicado para mejorar los síntomas de los pacientes con FA que siguen sintomáticos a pesar del tratamiento adecuado para el control de la frecuencia cardiaca. La combinación de antiarrítmicos que prolongan el intervalo QT no se debe emplear para el control del ritmo cardiaco en la FA(AU)

Atrial fibrillation (AF) is the most frequent sustained arrhythmia that can occur in a wide variety of clinical conditions. Despite progress in the treatment of patients with AF, this arrhythmia remains one of the most important causes of stroke, heart failure, sudden death and cardiovascular morbidity worldwide. The aim of treatment with antiarrhythmic drugs is to improve the symptoms related to AF, and to look for a balance between the symptomatic load, the possibility of adverse pharmacological reactions and the patient preferences. The short and long term heart rate control can be achieved with beta blockers, digoxin, calcium channel blockers or combination therapy. Although other class III antiarrhythmic drugs also have a frequency-limiting effect, they should only be used for the control of heart rhythm. Restoring and maintaining sinus rhythm is also an integral part of the treatment of AF. Class III antiarrhythmic drugs double the rate of patients who maintain their sinus rhythm. Treatment for rhythm control is indicated to improve the symptoms of patients with AF who remain symptomatic despite adequate treatment for heart rate control. The combination of antiarrhythmics that prolong the QT interval should not be used to control heart rhythm in AF(AU)

Interpretation of 2018 American Heart Association Focused Update on Pediatric Advanced Life Support:An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care / 中国实用儿科杂志

In November 2018,the American Heart Association(AHA) updated Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. The new guideline provided the evidence review and treatment recommendation for antiarrhythmic drug therapy in pediatric shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. The update was carried out by the Pediatrics Working Group of the International Liaison Committee on Resuscitation(ILCOR)for ongoing clinical evidence review. The update continues with the view of 2015's edition that either lidocaine or amiodarone may be used to treat pediatric patients with shock-refractory ventricular fibrillation or pulseless ventricular tachycardia. The flow chart of cardiac arrest for pediatric advanced life support was slightly adjusted.

Efecto electromecánico de los antiarrítmicos clase Ic durante el tratamiento de arritmias auriculares en cardiopatías congénitas / Electromechanical effect of Ic class antiarrhythmic drugs during the treatment of atrial arrhythmias in congenital heart diseases

Introducción: los fármacos antiarrítmicos son la primera línea de tratamiento para el control de las taquiarritmias en el paciente pediátrico. La terapéutica con drogas clase Ic en los pacientes con cardiopatías congénitas ha sido limitada, por los reportes que demostraron incremento de la mortalidad en los sujetos con cardiopatías estructurales. Objetivo: valorar el efecto de los antiarrítmicos clase Ic sobre los fenómenos electro-mecánicos cardiacos en los niños con cardiopatías congénitas con arritmias auriculares. Métodos: se realizó un estudio analítico, observacional, longitudinal y prospectivo en los pacientes con cardiopatías congénitas que desarrollaron arritmias auriculares, tratados con antiarrítmicos clase Ic en el Cardiocentro Pediátrico William Soler . Se analizaron variables electrocardiográficas, así como estimación de la función sistodiastólica mediante el ecocardiograma. Resultados: fueron evaluados 46 pacientes, 25 tratados con flecainida (grupo I) y 21 con propafenona (grupo II) durante 4,57±0,86 años. La taquicardia por reentrada intraatrial fue la arritmia de mayor incidencia (58,69 por ciento), mientras que, la tetralogía de Fallot, el defecto cardiaco más común (36,9 por ciento). Las variables electrocardiográficas no sufrieron variaciones nítidas durante el seguimiento. El análisis comparativo intragrupal demostró la preservación de la función sistólica en la totalidad de los sujetos (I, p= 0,275; II, p= 0,262). Comportamiento análogo exhibió la función diastólica, expresada en el índice de Tei (I, p= 0,244; II, p= 0,286). Conclusiones: la utilización de antiarrítmicos clase Ic en los pacientes pediátricos con cardiopatías congénitas no se asocia a largo plazo con alteraciones electrocardiográficas significativas ni compromiso de la función sistodiastólica, por lo que se recomienda su uso en esta población(AU)

Introduction: antiarrhythmic drugs are the first line of treatment for the control of tachyarrhythmias in pediatric patients. Therapy with Ic class drugs in patients with congenital heart disease has been limited, mainly due to reports that showed an increase in mortality in patients with structural heart disease. Objective: to assess the effect of Ic class antiarrhythmic drugs on cardiac electro-mechanical phenomena in children with congenital heart disease with atrial arrhythmias. Methods: an analytical, observational, longitudinal and prospective study was performed in patients with congenital heart diseases who developed atrial arrhythmias treated with Ic class antiarrhythmic drugs in William Soler Pediatric Cardiocenter. Electrocardiographic variables were analyzed, as well as the estimation of systo-diastolic function by echocardiography. Results: 46 patients were evaluated, 25 treated with flecainide (group I) and 21 with propafenone (group II) during 4.57 ± 0.86 years. The intra-atrial reentrant tachycardia was the arrhythmia with the highest incidence (58.69 percent); while tetralogy of Fallot was the most common cardiac defect (36.9 percent). The electrocardiographic variables did not undergo sharp variations during the follow-up. The intergroup comparative analysis showed the preservation of systolic function in all subjects (I, p= 0.275; II, p= 0.262). Analogous behavior showed diastolic function, that was expressed in the Tei index (I, p= 0.244; II, p= 0.286). Conclusions: the use of Ic class antiarrhythmic drugs in pediatric patients with congenital heart disease is not associated in the long term with significant electrocardiographic alterations or compromise of systo-diastolic function, so its use is recommended in this population(AU)

Antiarrhythmic drug usage and prostate cancer: A population-based cohort study / 亚洲男科学杂志(英文版)

Even though the relationship between antiarrhythmic drug usage and subsequent prostate cancer (PCa) risk has recently been highlighted, relevant findings in the previous literature are still inconsistent. In addition, very few studies have attempted to investigate the association between sodium channel blockers or potassium channel blockers for arrhythmia and the subsequent PCa risk. Therefore, this cohort study aimed to find the relationship between antiarrhythmic drug usage and the subsequent PCa risk using a population-based dataset. The data used in this study were derived from the Longitudinal Health Insurance Database 2005, Taiwan, China. We respectively identified 9988 sodium channel blocker users, 3663 potassium channel blocker users, 65 966 beta-blocker users, 23 366 calcium channel blockers users, and 7031 digoxin users as the study cohorts. The matched comparison cohorts (one comparison subject for each antiarrhythmic drug user) were selected from the same dataset. Each patient was tracked for a 5-year period to define those who were subsequently diagnosed with PCa. After adjusting for sociodemographic characteristics, comorbidities, and age, Cox proportional hazard regressions found that the hazard ratio (HR) of subsequent PCa for sodium channel blocker users was 1.12 (95% confidence interval [CI]: 0.84-1.50), for potassium channel blocker users was 0.89 (95% CI: 0.59-1.34), for beta-blocker users was 1.08 (95% CI: 0.96-1.22), for calcium channel blocker users was 1.14 (95% CI: 0.95-1.36), and for digoxin users was 0.89 (95% CI: 0.67-1.18), compared to their matched nonusers. We concluded that there were no statistical associations between different types of antiarrhythmic drug usage and subsequent PCa risk.

Clinical value and safety of antiarrhythmic drugs in the treatment of atrial fibrillation / 中国生化药物杂志

Objective To investigate the clinical value and safety of cedilanid, esmolol in the treatment of atrial fibrillation. Methods From August 2014 to August 2016 our Hospital from 117 patients with atrial fibrillation clinical data, according to the random number distribution principle, the patients were divided into observation group 59 cases and control group of 58 cases, all patients were given the treatment of primary disease, the clinical symptoms, the patients in the observation group were given oxygen, has given furosemide, cedilanid, after micro injection pump intravenous nitroglycerin, 5-20 g/min. Start after the injection of nitroglycerin, establish another vein channel, every 30 min to 0.2 mg patients, the treatment group were treated with intravenous injection of small dose esmolol. The clinical efficacy, ventricular rate, systolic blood pressure, diastolic blood pressure and adverse reactions were observed in two groups. Results The early and late effective rates of the two groups were not significantly different. The observation showed that after treatment, the ventricular rate, systolic pressure and diastolic pressure in the observation group were significantly higher than those in the control group (P<0.05), and the incidence of adverse reactions in the two groups was significantly different (P<0.05). Conclusion High dose cedilanid combined with small dose esmolol in treatment of atrial fibrillation, obvious curative effect, high safety, can choose the appropriate application.

Introduction of ICH E14 Clinical Evaluation of QT Prolongation Caused by Non-Antiarrhythmic Drug: Q&As (R3) / 药物评价研究

To detect and determine the QT interval prolongation caused by non antiarrhythmic drugs,ICH released the E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs and released E14's questions and answers (ICH E14 Q&As) in 2008 which explained some specific questions.Subsequently,This Q&As were revised third times and in June 2017 forwarded by FDA.The number of questions and answers in the revised edition doubled compared with the original.This article introduces the details of this revised edition,and hopes to be helpful to the research and supervision in China.

Estado actual de la ablación de la fibrilación auricular / Current status on atrial fibrillation ablation

La fibrilación auricular es la arritmia más común en la práctica clínica. La ablación se considera el tratamiento de elección (indicación clase I) en los pacientes sintomáticos con recurrencias a pesar del tratamiento con fármacos antiarrítmicos. El presente artículo revisa tanto los mecanismos propuestos de esta arritmia como las diferentes metodologías de ablación con catéter y sus indicaciones.

Summary Atrial fibrillation is the most common arrhythmia in clinical practice. Catheter ablation is the treatment of choice (Class I indication) for symptomatic patients with recurrences despite antiarrhythmic drugs. The present article reviews the proposed mechanisms of this arrhythmia and the different ablation methods and indications.

The Role of Antiarrhythmics in Atrial Fibrillation / 대한내과학회지

Atrial fibrillation (Afib) is the most common arrhythmia with clinical significance, and its incidence increases with advanced age. Afib is associated with a 3- to 5-fold increased risk of stroke, a 3-fold increase in the risk of heart failure, and higher mortality than without Afib. The treatment of Afib is multifold but revolves around one essential issue: whether to attempt to restore sinus rhythm or to simply control the ventricular rate. This decision depends on symptom severity, the age of the patient, underlying heart disease, and other comorbidities that may limit therapeutic options. The management of Afib with antiarrhythmic medications was reviewed.

A case report with the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration due to cancer pain

Introduction: Paroxysmal atrial fibrillation (Paf) occurred in an inpatient who has been prescribed methadone for cancer pain in our palliative care unit, but oral administration of aprindine (antiarrhythmic agent) succeeded in defibrillation and methadone administration could be continued. Case: A 75-year-old man had developed multiple bone metastases after resection of thyroid cancer. Due to refractory cancer pain, switching from oxycodone to methadone was performed. Pain relief was achieved with methadone 40 mg/day and without QT interval prolongation. After methadone administration about 9 months, there suddenly became loss of appetite in the morning of one day. ECG examination revealed Paf onset. Aprindine 20 mg was orally administered for the purpose of defibrillation. After about 2 hours sinus rhythm was gained and later without recurrence. Conclusion: This case was considered to have the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration. If administration of antiarrhythmic agents is performed in a patient whom has been prescribed methadone, it is feared to lead to result in QT interval prolongation due to drug interactions. It is important to carefully select an agent that rarely leads to QT prolongation.

Síndrome de Bayés: valor del electrocardiograma en la predicción de fibrilación auricular

El síndrome de Bayés refiere a la asociación entre el bloqueo interauricular avanzado y la fibrilación auricular (FA). Este simple parámetro electrocardiográfico, sencillo de aprender, es útil para identificar pacientes con alto riesgo de presentar una nueva FA o recurrencias luego de instaurado el tratamiento antiarrítmico (fármacos, cardioversión o ablación). Una vez detectado el patrón clásico del trastorno de la conducción interauricular, debe realizarse una pesquisa meticulosa en busca de FA. El síndrome de Bayés es un epónimo en reconocimiento al genial catalán que ha descrito la fisiopatología, las manifestaciones clínico-electrocardiográficas, la asociación con arritmias supraventriculares y los posibles tratamientos.

Electrofisiología, mecanismos moleculares y '-ómicas' de la fibrilación atrial: Bases para una medicina personalizada / Electrophysiology, molecular mechanisms and '-omics' of the atrial fibrillation: Basis for personalized medicine / Eletrofisiologia, mecanismos moleculares e '-ómicas' da fibrilação atrial: Bases para uma medicina personalizada

La fibrilación atrial (FA) es una arritmia muy frecuente, con una prevalencia que aumenta con el envejecimiento. Su perpetuación es un factor determinante en la aparición de eventos cardiovasculares, generando un mayor número de complicaciones y mortalidad. Diversas condiciones contribuyen a cambios progresivos de la electrofisiología atrial, incluyendo tres componentes: eléctricos (canales iónicos y homeostasis de Ca2+), estructurales (hipertrofia/fibrosis tisular) y uniones Gap. Éstos pueden favorecer la aparición de factores desencadenantes, así como la formación de sustratos que favorecen su perpetuación; además, condicionan un incremento en la actividad ectópica espontánea y generación de reentradas. Actualmente, estudios genómicos han identificado regiones de susceptibilidad para FA, y estudios de clivaje familiar (screening) han descubierto formas monogénicas, así como mutaciones aberrantes. En esta revisión, se explora en profundidad los mecanismos moleculares de la FA, integrando diversos aspectos clínico-epidemiológicos, su genómica y electrofisiopatología. Destacando, como enfermedades cardíacas, factores extracardíacos y una regulación génica anormal conducen a la arritmia. Concluyéndose con una discusión sobre las implicaciones terapéuticas que podrían conducir a un tratamiento personalizado en el siglo XXI.

Atrial fibrillation (AF) is a common arrhythmia, with a prevalence increases with aging. Its perpetuation is a determining factor in the occurrence of cardiovascular events, generating a great number of complications and mortality. Several conditions contribute to progressive changes of atrium electrophysiology, including three components: electrical (ion channels function, Ca2+ homeostasis), structural (hypertrophy and tissue fibrosis) and gap junctions. These may trigger events that initiate the arrhythmia, promote its perpetuation; also they determine an increase in spontaneous ectopic activity and generation of reentry. Recently, numerous genomic studies have identified hotspots with increased susceptibility to AF, and linkage analyses have uncovered unique monogenic and deleterious mutations. This review deeply focuses on the molecular mechanisms of AF; exploring the relationship between clinical-epidemiological, genomics and electropathophysiology aspects. Relevantly, how cardiac states, extracardiac factors, and abnormal gene expression result in this arrhythmia. We conclude with a discussion of the potential therapeutic repercussions that might lead to personalized treatment in the XXI century.

A fibrilação atrial (FA) é uma arritmia terra comum, com uma prevalência aumenta com a idade. Sua perpetuação é um fator determinante para a ocorrência de eventos cardiovasculares, gerando um grande número de complicações e mortalidade. Várias condições contribuem para mudanças progressistas na eletrofisiologia atrial, incluindo três componentes: elétrico (canais iônicos e homeostase do Ca2+), estruturais (hipertrofia/fibrose tecidual) e junções gap. Estes podem promover o desenvolvimento de gatilhos, e a formação de substratos que favorecem sua perpetuação; também determinam um aumento na atividade ectópica espontânea e geração de reentrada. Atualmente, estudos genômicos têm identificado regiões de suscetibilidade à FA, e estudos de clivagem familiar (screening) têm encontrado formas monogênicas e mutações aberrantes. Nesta revisão vamos explorar em profundidade os mecanismos moleculares da FA, integrando vários aspectos clínico-epidemiológicos, genômicos e eletrofisiopatológico. Destacando tais como doença cardíaca, fatores extracardíacos e alterações na expressão de genes levando a arritmia. Concluindo com uma discussão sobre as implicações terapêuticas que poderiam levar a um tratamento personalizado no século XXI.

Real-World Observations with Dronedarone Compared to Other Anti-Arrhythmic Drugs in Recurrent Atrial Fibrillaton.

Background: Many clinical trials have shown that dronedarone which is a potent ion channels blocker is effective in the prevention of atrial fibrillation (AF) relapses. Objective: The aim of this report is to evaluate the recurrence of AF and safety during therapy with dronedarone. Methods: From September 2010 to February 2013, 95 patients with recurrent AF were followed by our department. The mean age was 71. Fifty-two were male (55%). All patients were in class NHYA I-II with paroxysmal or persistent AF. Hepatic enzymes were controlled after 1, 3, and 6 months of therapy. Results: Structural heart diseases were present in 90.5% of patients; 9.5% of patients had lone AF. We observed recurrences of AF in 37.9% of patients treated with dronedarone compared with 39% of patients treated with propafenone or flecainide, 35% of patients treated with sotalol and 25% of patients treated with amiodarone. Using log-rank Mantel-Cox test there are no statistical significant differences between dronedarone and IC anti-arrhythmic drugs and sotalol (p 0.743; p 0.868). Conclusion: According to guidelines, dronedarone resulted as effective as other anti-arrhythmic drugs (except amiodarone) in the prevention of AF with the advantage that it may be safely used in a greater number of patients (including elderly patients with structural heart diseases).

EFECTO DEL FÁRMACO CLOROQUINA EN LA TERMINACIÓN DE UN ROTOR DURANTE FIBRILACIÓN AURICULAR PAROXÍSTICA. ESTUDIO DE SIMULACIÓN / CHLOROQUINE DRUG EFFECT ON A ROTOR TERMINATION DURING PAROXYSMAL ATRIAL FIBRILLATION. A SIMULATION STUDY / O EFEITO DO MEDICAMENTO CLOROQUINA NO FECHAMENTO DE UM ROTOR DURANTE FIBRILAÇÃO ATRIAL PAROXÍSTICA. SIMULAÇÃO ESTUDO

La fibrilación auricular (FA) es la arritmia más común. Algunos episodios de FA son mantenidos por rotores. La FA paroxística (FAp) se refiere a episodios recurrentes que se autolimitan. Si la FAp no se trata puede convertirse en crónica. Se ha demostrado que la inhibición de las corrientes I KACh e I K1 contribuye a la terminación de la FA. El fármaco antimalárico cloroquina, al inhibir estas corrientes podría ser un fármaco antiarrítmico eficaz en humanos. El objetivo del trabajo es simular los efectos de la cloroquina y estudiar su eficacia en la terminación de un rotor en condiciones de FAp. Para esto, se desarrolló un modelo 2D de tejido auricular en condiciones de FAp. Se implementó un modelo del efecto de la cloroquina sobre las corrientes I K1 e I KACh para estudiar su eficacia en la terminación de un rotor simulado. La cloroquina alargó el potencial de acción a medida que se incrementó su concentración. A concentraciones de 0.3 µM y superiores, finalizó la actividad del rotor. Este es el primer trabajo que ha desarrollado modelos matemáticos del fármaco cloroquina para estudiar su efecto en la terminación de un rotor. Los resultados sugieren que la cloroquina podría ser un potente agente antiarrítmico en el tratamiento de la FAp.

Atrial fibrillation (AF) is the most common arrhythmia. Some AF episodes are maintained by rotors. Paroxysmal AF (pAF) refers to self-limiting recurrent episodes. If the pAF is not treated it could become chronic. It has been demonstrated that inhibition of the I K1 and I KACh currents contributes to AF termination. Antimalarial drug chloroquine by inhibiting these currents could be an effective antiarrhythmic drug in humans. The aim of this work is to simulate the effects of chloroquine and study their effectiveness in the rotor termination in pAF conditions. For this, we developed a 2D model of atrial tissue under pAF conditions. We implemented a model of the effect of chloroquine on I K1 and I KACh currents to study its effectiveness in the termination of a simulated rotor. Chloroquine lengthened the action potential as the concentration increased. At concentrations of 0.3 µM and higher, the activity of the rotor finished. This is the first work that developed a chloroquine mathematical models to study its effect on the rotor termination. The results suggest that chloroquine could be a potent antiarrhythmic drug for the pAF treatment.

A fibrilhação auricular (FA) é a arritmia mais comum. Alguns episódios de FA são mantidos por rotores. A FA paroxística (FAp) refere-se a episódios recorrentes que são autolimitantes. Se a FAP não tem nenhum tratamento, pode se tornar crônica. Tem sido demonstrado que a inibição das correntes I KACh e I K1 contribui para o término da AF. O medeicamento antimalárico cloroquina, para inibir essas correntes poderia ser um medicamento anti-arrítmico eficaz em seres humanos. O objetivo deste trabalho é simular os efeitos da cloroquina e estudar a sua eficácia na terminação de um rotor capaz em condições FAp. Para isso, um modelo 2D foi desenvolvido de tecido auricular em condições de FAp. foi implementado um modelo do efeito da Cloroquina sobre as corrente I K1 e I KACh para estudar a sua eficácia na terminação de um rotor simulado. A Cloroquina alongou o potencial de ação na medida em que foi aumentada a sua concentração. Em concentrações de 0,3 µM e superiores, terminou a atividade do rotor. Este é o primeiro trabalho que desenvolveu modelos matemáticos do medicamento cloroquina para estudar seu efeito sobre a terminação de um rotor. Os resultados sugerem que a cloroquina poderia ser um potente agente anti-arrítmico para o tratamento de FAp.

Antidysrhythmic Effects of Gallic acid on cacl2-induced arrhythmia in rat.

In many cases, myocardial infarction leads to arrhythmia. Since antioxidant agents play an important protective role in heart disease, therefore, many of them are used as medicinal plants in traditional medicine. Gallic acid, as a potent antioxidant agent, was shown many preventive effects on diseases; therefore, the aim of this study was the evaluation of antidysrhythmic effects of gallic acid on CaCl2-induced arrhythmia in rat. Forty male Sprague-dawley rats (200-250 gr) were divided into 5 groups included: control (N/S, 1ml/kg, gavage, 10 days), GA (10, 30, 50 mg/kg, gavage, for 10 days), quinidine (50mg/kg, iv). In all chronic groups before experiments and 10 days later, lead II electrocardiogram was recorded for calculating HR. The arrhythmia was produced by i.v. injection of a solution CaCl2 (140 mg/kg) at time effect peak chemical antiarrhythmias drugs. Then percentage of Ventricular premature beats (VPB), Ventricular fibrillation (VF) and Ventricular tachycardia (V.tach) were recorded. Results were analyzed by using t-test, one-way ANOVA and FISHER exact test. P<0.05 was considered as significant level. The chronotropic effect was not significant with GA after 10 days. GA displayed antidysrhythmic effects on CaCl2-induced arrhythmia with the highest activity at the medium dose of 50 mg/kg, compared to Control group by significant reduction of VPB, VF and V.tach comparable to that of quinidine as a chemical anti arrhythmias drug. GA considered as an antiarrhythmic agent because of reduces the incidence of VPB, Vtac and VF. Results suggest a protective role of GA against heart disease.

Some clinical problems of first-aid medicines on severe cardiac arrhythemias in children / 中国小儿急救医学

Severe cardiac arrhythmias is not rare in chilaren.Because they usually induce striking disturbance of the blood dynamics,heart failure,cardiogenic shock,Adams-stokes attack or sudden death can happen in sick child,therefore they belong to pediatric emergency.Though cardioversion-defibrillation and cardiac pacemaker implantation are widely applied to clinical practice recently,antiarrhythmic drugs are still the most common treatment method at present.In this article,dose and usage,harmful reactions,indications and contraindications of common fist-aid medicines would be introduced,and some important problems in clinical use also be discussed.