Protective Effect of Combined Metoprolol and Atractylenolide I in Rats with Acute Myocardial Infarction via Modulation of the SIRT3/ß-CATENIN/PPAR-γ Signaling Pathway

ABSTRACT Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/ß-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, ß-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, ß-catenin, and PPAR-γ

Evaluation of anticholinergic burden in elderly outpatients and the risk factors / 中南大学学报(医学版)

OBJECTIVES@#The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs.@*METHODS@#A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia.@*RESULTS@#A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine).@*CONCLUSIONS@#There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Quality control and drug-drug interactions between commercially available Metoprolol and Glimepiride tablets

Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.

Segurança, Eficácia e Protocolo de Dose de Metoprolol para Redução de Frequência Cardíaca em Pacientes Pediátricos Externos que Passaram por Angiografia Cardíaca por TC / Safety, Efficacy, and Dose Protocol of Metoprolol for Heart Rate Reduction in Pediatric Outpatients Undergoing Cardiac CT Angiography

Resumo Fundamento Qualidade de imagem e dose de radiação são otimizadas com uma frequência cardíaca (FC) lenta e estável na realização de imagens de artérias coronárias durante a angiografia cardíaca por tomografia computadorizada (CCTA, do inglês cardiac computed tomography angiography) A segurança, a eficácia e o protocolo para a redução da FC com medicamento betabloqueador ainda não foi bem descrita em uma população de pacientes pediátricos. Objetivo Oferecer um protocolo de dose de metoprolol eficiente a ser usado em pacientes pediátricos externos durante a CCTA. Métodos Realizamos uma revisão retrospectiva de todos os pacientes pediátricos externos que receberam o metoprolol durante a CCTA. As características demográficas e clínicas foram resumidas e a redução média em FC foi estimada utilizando-se um modelo de regressão linear multivariada. As imagens foram avaliadas em uma escala de 1 a 4 (1= ideal). Resultados Um total de 78 pacientes externos passaram a uma CCTA com o uso de metoprolol. A média de idade foi de 13 anos, a média de peso foi de 46 kg, e 36 pacientes (46%) eram do sexo masculino. As doses médias de metoprolol foram 1,5 (IQR 1,1; 1,8) mg/kg, e 0,4 (IQR 0,2; 0,7) mg/kg para administrações orais e intravenosas, respectivamente. O produto dose-comprimento por exame foi de 57 (IQR 30, 119) mGy*cm. A redução média da FC foi 19 (IQR 12, 26) batimentos por minuto, ou 23%. Não foram relatadas complicações ou eventos adversos. Conclusão O uso de metoprolol num cenário de pacientes pediátricos externos para redução da FC antes de uma CCTA é seguro e eficiente. Pode-se reproduzir um protocolo de dose de metoprolol quando for necessário atingir uma FC mais lenta, garantindo tempos de aquisição mais rápidos, imagens mais claras e redução na exposição à radiação nessa população. (Arq Bras Cardiol. 2021; 116(1):100-105)

Abstract Background Image quality and radiation dose are optimized with a slow, steady heart rate (HR) when imaging the coronary arteries during cardiac computed tomography angiography (CCTA). The safety, efficacy, and protocol for HR reduction with beta blocker medication is not well described in a pediatric patient population. Objective Provide a safe and efficient metoprolol dose protocol to be used in pediatric outpatients undergoing CCTA. Methods We conducted a retrospective review of all pediatric outpatients who received metoprolol during CCTA. Demographic and clinical characteristics were summarized and the average reduction in HR was estimated using a multivariate linear regression model. Images were evaluated on a 1-4 scale (1= optimal). Results Seventy-eight pediatric outpatients underwent a CCTA scan with the use of metoprolol. The median age was 13 years, median weight of 46 kg, and 36 (46%) were male. The median doses of metoprolol were 1.5 (IQR 1.1, 1.8) mg/kg and 0.4 (IQR 0.2, 0.7) mg/kg for oral and intravenous administrations, respectively. Procedural dose-length product was 57 (IQR 30, 119) mGy*cm. The average reduction in HR was 19 (IQR 12, 26) beats per minute, or 23%. No complications or adverse events were reported. Conclusion Use of metoprolol in a pediatric outpatient setting for HR reduction prior to CCTA is safe and effective. A metoprolol dose protocol can be reproduced when a slower HR is needed, ensuring faster acquisition times, clear images, and associated reduction in radiation exposure in this population. (Arq Bras Cardiol. 2021; 116(1):100-105)

Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy / 中华医学杂志(英文版)

BACKGROUND@#Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.@*METHODS@#This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of  0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013).@*CONCLUSIONS@#Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.

Análise da Segurança e Exequibilidade do Ecocardiograma sob Estresse com Dobutamina em Dez Mil e Seis Exames de uma População Geral / Analysis of the Safety and Feasibility of Dobutamine Stress Echocardiography in Ten Thousand and Six Tests of a General Population

Fundamento: Durante o ecocardiograma sob estresse com dobutamina, podem ocorrer efeitos adversos e exames inconclusivos. Objetivo: Avaliar em uma grande população geral a segurança e a exequibilidade do ecocardiograma sob estresse com dobutamina. Métodos: Estudo de 10.006 ecocardiogramas sob estresse com dobutamina realizados no período de julho de 1996 a setembro de 2007. A dobutamina foi administrada em quatro estágios (10, 20, 30 e 40 µcg.kg-1.min-1) para pesquisa de isquemia miocárdica e iniciada com 5 µcg.kg- ¹.min-1 apenas na análise de viabilidade miocárdica. A atropina foi iniciada conforme os protocolos vigentes. Foram verificados dados clínicos, hemodinâmicos e efeitos adversos associados ao ecocardiograma sob estresse com dobutamina. Resultados: Durante os ecocardiogramas sob estresse com dobutamina, ocorreu angina típica (8,9%), pico hipertensivo (1,7%), ectopias ventriculares isoladas (31%), taquiarritmia supraventricular (1,89%), fibrilação atrial (0,76%) e taquicardia ventricular não sustentada (0,6%). Os efeitos adversos citados foram mais frequentes nos pacientes com ecocardiogramas sob estresse com dobutamina positivos para isquemia. A desaceleração sinusal paradoxal (0,16%) não ocorreu em ecocardiogramas sob estresse com dobutamina positivo. As três complicações graves ocorreram em ecocardiogramas sob estresse com dobutamina positivos para isquemia. Foram dois casos (0,02%) com fibrilação ventricular e um caso de síndrome coronariana aguda (0,01%). Não houve caso de taquicardia ventricular sustentada, ruptura cardíaca, assistolia ou óbito. Comparados aos exames concluídos, nos inconclusivos, os pacientes usaram menos atropina (81,5% versus 49,9%; p< 0,001) e mais betabloqueador (4,7% versus 19%; p< 0,001), apresentando mais pico hipertensivo (1,1% versus 14,2%; p = 0,0001) e taquicardia ventricular não sustentada (0,5% versus 2,2%; p< 0,001). Conclusão: O ecocardiograma sob estresse com dobutamina realizado de forma apropriada é seguro e apresenta elevada exequibilidade.

Background: Adverse effects and inconclusive results may occur on dobutamine stress echocardiography. Objective: To assess the safety and feasibility of dobutamine stress echocardiography in a large general population. Methods: A total of 10,006 dobutamine stress echocardiographies were performed between July 1996 and September 2007. Dobutamine was administered in four stages (10, 20, 30, and 40 µcg·kg-1·min-1) to research myocardial ischemia starting with 5 µcg·kg- ¹·min-1 to analyze myocardial viability. Atropine administration was initiated according to current protocols. Clinical, hemodynamic, and adverse effect data associated with dobutamine stress echocardiography findings were verified. Results: Typical angina (8.9%), hypertensive peak (1.7%), isolated ventricular ectopias (31%), supraventricular tachyarrhythmia (1.89%), atrial

Effects of CYP2D610 on plasma trough concentration of metoprolol in patients with coronary artery disease / 南方医科大学学报

OBJECTIVE@#To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease.@*METHODS@#The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes.@*RESULTS@#In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them.@*CONCLUSIONS@#CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.

Metoprolol treatment of dual cocaine and bupropion cardiovascular and central nervous system toxicity

Cardiovascular and central nervous system (CNS) toxicity, including tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion use. We report acute toxicity from the concomitant use of cocaine and bupropion in a 25-year-old female. She arrived agitated and uncooperative, with a history of possible antecedent cocaine use. Her electrocardiogram demonstrated tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses of 5 mg intravenous metoprolol were administered, which resolved the agitation, tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive toxicology screen returned positive for both cocaine and bupropion. We believe clinicians should be aware of the potential for synergistic cardiovascular and CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent an effective initial treatment. Unlike benzodiazepines, metoprolol directly counters the pharmacologic effects of stimulants without respiratory depression, sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has good penetration of the CNS and can counter stimulant-induced agitation.

Taquicardia ventricular idiopática em portador de miocárdio não compactado / Idiopathic ventricular tachycardia in patient with noncompacted myocardium

Relatamos o caso de paciente do sexo masculino, com 23 anos de idade, portador de miocárdio não compactado e taquicardia ventricular monomórfica sustentada. O paciente foi submetido a implante de cardiodesfibrilador implantável após diagnóstico confirmado por meio de ressonância nuclear magnética cardíaca e mantido em tratamento clínico com medicação antiarrítmica, sem recorrência de arritmia ventricular no acompanhamento ambulatorial

We report the case of a 23-year-old male patient with noncompacted myocardium and sustained monomorphic ventricular tachycardia. The patient was submitted to mplantable cardioverter defibrillator after diagnosis confirmed by cardiac magnetic resonance imaging and was kept on clinical treatment with antiarrhythmic medication without the recurrence of ventricular arrhythmia in the outpatient follow-up

TeleCondutas: hipertireoidismo / TeleGuides: hyperthyroidism

Hipertireoidismo é o excesso de função da glândula tireoide. É a principal causa de tireotoxicose, que, por sua vez, é a manifestação clínica do excesso de hormônios tireoidianos. O hipertireoidismo é mais comum em mulheres do que em homens (razão de 5:1), tendo como principais causas a Doença de Graves (60 % a 80% dos casos), etiologia típica em mulheres jovens com idade entre 20 a 40 anos, e o bócio multinodular tóxico (10 % a 30% dos casos), mais frequente em idosos. O adenoma tóxico e as tireoidites são menos comuns (1%). Hipertireoidismo e tireotoxicose também podem ser induzidos por medicamentos como amiodarona, interferon, levotiroxina e lítio. A doença deve ser investigada em pacientes com manifestações clínicas, não havendo recomendação para rastreamento populacional. Informações sobre tireotoxicose induzida por levotiroxina (TSH reduzido em paciente que faz uso de levotiroxina) podem ser obtidas no material TeleCondutas Hipotireoidismo. Esta guia apresenta informação que orienta a conduta para casos de hipertiroidismo no contexto da Atenção Primária à Saúde, incluindo: sinais e sintomas, diagnóstico do hipertireoidismo, tratamento do hipertireoidismo, tratamento do hipertireoidismo subclínico, hipertireoidismo na gestação, encaminhamento para serviço especializado.

Desenvolvimento de sistemas multiparticulados de liberação imediata e modificada para associação de fármacos anti-hipertensivos / Development of immediate and modified release multiparticulate systems for antihypertensive drugs association

Os sistemas multiparticulados são aqueles nos quais a dose do fármaco está dividida em pequenas unidades funcionais, tendo assim, uma série de vantagens sobre os sistemas monolíticos convencionais. Este trabalho teve por objetivo desenvolver formulações multiparticuladas de uso oral para fármacos anti-hipertensivos que serão utilizados na composição de associações. O material está dividido em seis capítulos, sendo inicialmente apresentada uma revisão da literatura a respeito da caracterização física destas pequenas unidades. Ensaios como análise granulométrica, morfologia, densidade, porosidade, avaliação de resistência mecânica e desintegração são os mais empregados para esta finalidade, possibilitando ao formulador conhecer os fatores de maior impacto relacionados às matérias primas e ao processo de fabricação no comportamento das formulações produzidas. Os demais capítulos seguem com o desenvolvimento dos sistemas multiparticulados, que foram embasados em diferentes delineamentos experimentais, seja pela utilização de planejamento fatorial fracionado ou projeto de mistura. Para o metoprolol, fármaco de alta solubilidade, foram produzidas formulações de liberação controlada, sendo a estratégia dividida em três etapas: (I) Produção de minicomprimidos revestidos, nos quais foram avaliadas diferentes combinações do polímero modulador de liberação; (II) otimização do perfil de liberação do fármaco, com avaliação de misturas das formulações produzidas na primeira etapa; (III) Processo de extrusão a quente, no qual diferentes proporções de fármaco e polímero hidrofóbico foram avaliadas. Para os fármacos hidroclorotiazida e olmesartana medoxomila, ambos de baixa solubilidade, a estratégia adotada foi a incorporação de uma dispersão dos fármacos e agentes solubilizantes em grânulos inertes obtidos por extrusão/revestimento. Adicionalmente, também foram produzidas formulações por extrusão a quente de diferentes proporções destes fármacos em polímero hidrofílico. De acordo com os resultados obtidos, foi possível obter formulações de minicomprimidos e grânulos com perfil de dissolução satisfatório, semelhantes aos apresentados pelos medicamentos adotados como referência. Em relação à extrusão a quente foi possível avaliar a influência do processo e polímeros empregados no perfil de dissolução dos grânulos produzidos

Multiparticulate systems are dosage forms in which dose is divided into small functional units presenting some advantages over monolithic conventional systems. The objective of this work was developing multiparticulate formulations for oral use containing antihypertensive drugs to be used in association. The thesis is divided into six issues, been first presented a literature review about physical characterization of multiparticulate systems. Granulometric analysis, morphology, density, porosity, mechanical strength and disintegration are the most used physical characterization tests, enabling formulator knowing the major impact factors related to raw materials and manufacturing process in the performance of the produced formulations. The other issues present the development of the multiparticulate systems based on different statistical experimental design, as fractional factorial design or mixture project. For metoprolol, a highly soluble drug, controlled release formulations were obtained, and the strategy was divided into three steps: (I) coated minitablets production, where different combinations of the controlled release polymer were analyzed; (II) drug release profile optimization, evaluating formulations mixtures produced in the first step; (III) hot melt extrusion process, where different drug: hydrophobic polymer ratios were evaluated. For hydrochlorothiazide and olmesartan medoxomil, both low soluble drugs, the strategy was incorporating a dispersion containing the drugs and solubilizing agents in inert granules obtained by extrusion/coating processes. Additionally, formulations containing different ratios of these drugs and hydrophilic polymers were produced by hot melt extrusion. According to the results, it was possible to obtain minitablets and granules with good dissolution profile, similar to the reference products. Regarding to hot melt extrusion, it was possible to evaluate the influence of process and polymers used in the dissolution profile of the produced granules

An extremely rare case of primary aorto-enteric fistula in a Filipino patient

INTRODUCTION: An  aorto-enteric  fistula  is  a  fistulous communication  between  the  duodenum  and  the  aorta. The  non-traumatic  form,  or  primary  aorto-enteric  fistula (PAEF), is rare and fatal if untreated.  This is a case of PAEF in a Filipino patient who presented with upper gastrointestinal bleeding (UGIB).CLINICAL PRESENTATION: A  62-year-old  Filipino  sought consult  for  hematemesis  and  melena.  He  had  just  been discharged the previous day and sent home on empiric H. pylori eradication therapy after a week of workup, which included an unremarkable esophagogastroduodenoscopy (EGD). He claimed to be hypertensive but was not taking any maintenance anti-hypertensive medication. PHYSICAL FINDINGS: Blood  pressure  was  80/50  mmHg,and  cardiac  rate  of  94  bpm.  He  had  pale  palpebral  conjunctivae,  and  pale  nailbeds.Abdominal  exam  was  unremarkable.  Rest  of  physical  exam  was  normal.  Stat hemoglobin was 63 g/dL. RESULTS: Exploratory  laparotomy  revealed  the  primary aortoduodenal  fistula  at  the  anterolateral  aspect  of  the fourth  segment  of  the  duodenum  (PADF).  Patient  was  started  on  metoprolol  and  atorvastatin.  Axillary  femoro-femoral  bypass,  ligation  of  aorta,  wedge  resection  of  aortoduodenal fistula, duodenorrhaphy, tube jejunostomy completed  was  done.  Post-operative  course  was  complicated by peritonitis and sepsis, and eventually went into arrest on his third week.SIGNIFICANCE: This is the first case of PAEF in our institution,and possibly in the country. It is an extremely rare condition that has an annual incidence of 0.007 per million. Since its description in 1843, only 250 cases have been reported in literature.RECOMMENDATIONS: A  high  index  of  suspicion  is  key  to  its diagnosis  and  management.Massive  UGIB,  a  negative  endoscopy, and known aortic aneurysm should raise the suspicion  for  PAEF,  as  prompt  surgical  intervention  is  the only chance for survival among these patients.

Lidocaine alleviates propofol related pain much better than metoprolol and nitroglycerin / Lidocaína é mais eficaz do que metoprolol e nitroglicerina para o alívio da dor relacionada à injeção de propofol

ABSTRACTBACKGROUND AND OBJECTIVES: Injection pain after propofol administration is common and maydisturb patients' comfort. The aim of this study was to compare effectiveness of intravenous(iv) nitroglycerin, lidocaine and metoprolol applied through the veins on the dorsum of hand orantecubital vein on eliminating propofol injection pain.METHOD: There were 147 patients and they were grouped according to the analgesic adminis-tered. Metoprolol (n = 31, Group M), lidocaine (n = 32, Group L) and nitroglycerin (n = 29, GroupN) were applied through iv catheter at dorsum hand vein or antecubital vein. Pain was evalu-ated by 4 point scale (0 - no pain, 1 --- light pain, 2 --- mild pain, 3 --- severe pain) in 5, 10, 15and 20th seconds. ASA, BMI, patient demographics, education level and the effect of pathwaysfor injection and location of operations were analyzed for their effect on total pain score.RESULTS: There were no differences between the groups in terms of total pain score (p = 0.981).There were no differences in terms of total pain score depending on ASA, education level,location of operation. However, lidocaine was more effective when compared with metoprolol(p = 0.015) and nitroglycerin (p = 0.001) among groups. Although neither lidocaine nor metopro-lol had any difference on pain management when applied from antecubital or dorsal hand vein(p > 0.05), nitroglycerin injection from antecubital vein had demonstrated statistically lowerpain scores (p = 0.001).CONCLUSION: We found lidocaine to be the most effective analgesic in decreasing propofolrelated pain. We therefore suggest iv lidocaine for alleviating propofol related pain at operations.

RESUMOJUSTIFICATIVA E OBJETIVOS: A dor no local da injeção após a administração de propofol é comum e pode causar desconforto nos pacientes. O objetivo deste estudo foi comparar a eficácia de nitroglicerina, lidocaína e metoprolol, aplicados intravenosamente através de veias do dorso das mãos ou antecubitais, para eliminar a dor causada pela injeção de propofol.MÉTODOS: Foram alocados em grupos 147 pacientes de acordo com o analgésico administrado: metoprolol (n = 31, Grupo M), lidocaína (n = 32, Grupo L) e nitroglicerina (n = 29, Grupo N). Os analgésicos foram aplicados via cateter intravenoso em veia do dorso da mão ou antecubital. A dor foi avaliada com uma escala de quatro pontos (0 = sem dor, 1 = dor leve, 2 = dor moderada, 3 = dor intensa) nos segundos cinco, 10, 15 e 20. Os dados demográficos dos pacientes, estado físico ASA, IMC, nível de escolaridade, efeito das vias de injeção e local das cirurgias foram analisados quanto a seus efeitos no escore total de dor.RESULTADOS: Não houve diferença entre os grupos em relação ao escore total de dor (p = 0,981). Não houve diferença no escore total de dor em relação ao estado físico ASA, escolaridade e local da cirurgia. No entanto, lidocaína foi mais eficaz em comparação com metoprolol (p = 0,015) e nitroglicerina (p = 0,001), na comparação entre os grupos. Embora lidocaína e metoprolol não tenham apresentado diferença no tratamento da dor quando aplicados em veia antecubital ou do dorso da mão (p > 0,05), a injeção de nitroglicerina em veia antecubital apresentou escores de dor estatisticamente menores (p = 0,001).CONCLUSÃO: Lidocaína mostrou-se como analgésico mais eficaz para diminuir a dor relacionada à injeção de propofol. Sugerimos, portanto, lidocaína IV para aliviar a dor relacionada à injeção de propofol em operações.

Efeito aditivo do transplante de células-troncos adultas sobre a perfusão cardíaca pós-infarto em porcos tratados com beta-bloqueador e inibidor da enzima conversora de angiotensiva / Additive effect of transplantation of adult stem cells post-infarction on the cardiac perfusion in pigs treated with beta-blocker and angiotensin-converting enzyme inhibitor

Os efeitos benéficos associados à injeção intramiocárdica de células-tronco adultas, obtidos em roedores, não tem sido reproduzidos de modo consistente em modelos animais de grande porte e seres humanos. Neste trabalho testamos a hipótese que o transplante de células-tronco mesenquimais derivadas do tecido adiposo de porcos (pASC) aumenta a perfusão tecidual cardíaca em animais infartados e humanizados pelo tratamento com um inibidor da enzima conversora de angiotensina (iECA) e um ?-bloqueador. Os animais foram submetidos a oclusão da artéria coronária circunflexa esquerda (ACX) e 4 semanas após o IM, 4 grupos foram randomizados para receber injeção intramiocárdica de pASC nas doses de 1, 2 ou 4x10 ...

The beneficial effects associated with intramyocardial injection of adult stem cells in rodents have not been consistently reproduced in larger animals and humans. We evaluated the dose of porcine adipose-tissue derived mesenchymal stem cells (pASC) to increase cardiac tissue perfusion in pigs treated with ace-inhibitors and ?-blockers to mimic human management post-MI. Animals were subjected to LCx occlusion and 4 weeks after MI blinded randomized in 4 groups to receive intramyocardial injection of pASC (1, 2 and 4x10 ...

Nebivolol in preventing atrial fibrillation following coronary surgery in patients over 60 years of age / Nebivolol na prevenção da fibrilação atrial após a cirurgia coronária em pacientes acima de 60 anos de idade

Objective: Postoperative atrial fibrillation is a common complication after cardiac surgery, with an incidence as high as 20-50%. Increased age is associated with a significant increase in postoperative atrial fibrillation risk. This common complication is associated with higher morbidity and mortality rates. The aim of this study was to assess the efficacy of nebivolol in preventing atrial fibrillation following coronary artery bypass surgery in patients over 60 years of age. Methods: In this prospective randomized study, 200 patients who were candidates for elective coronary artery bypass surgery were divided into two groups. The first group was administered with nebivolol and the second group was administered with metoprolol. Treatment was initiated four days prior to surgery, and patients were monitored for atrial fibrillation until discharge. Forty-one patients recieved 50 mg metoprolol succinate daily, which was initiated minimum 4 days before surgery. Results: Demographic data were similar in both groups. The incidence of postoperative atrial fibrillation in both groups was similar, with no significant difference being identified [n=20 (20%); n=18 (18%), P=0.718; respectively]. There were not any mortality at both groups during study. Inotropic agent requirement at ICU was similar for both groups [n=12 (12%), n=18 (18%), P=0.32]. Conclusion: We compared the effectiveness of nebivolol and metoprolol in decreasing the incidence of postoperative atrial fibrillation, and determined that nebivolol was as effective as metoprolol in preventing postoperative atrial fibrillation at patients. Nebivolol may be the drug of choice due to its effects, especially after elective coronary artery bypass surgery. .

Objetivo: Pós-operatório fibrilação atrial é uma complicação comum após a cirurgia cardíaca, com uma incidência tão elevada quanto 20-50%. O aumento da idade está associado com elevação significativa no risco de pós-operatório da fibrilação atrial. Esta complicação comum é associada com taxas de morbidade e mortalidade. O objetivo deste estudo foi avaliar a eficácia do nebivolol na prevenção da fibrilação atrial após cirurgia de revascularização do miocárdio de pacientes acima de 60 anos de idade. Métodos: Neste estudo prospectivo e randomizado, duzentos pacientes candidatos à cirurgia de revascularização do miocárdio foram divididos em dois grupos. O primeiro grupo foi administrado com nebivolol e o segundo grupo, com metoprolol. O tratamento foi iniciado quatro dias antes da cirurgia, e os pacientes foram monitorados para fibrilação atrial até a alta. Quarenta e um pacientes receberam 50 mg de sucinato de metoprolol diário, que foi iniciado, no mínimo, 4 dias antes da cirurgia. Resultados: Os dados demográficos foram semelhantes nos dois grupos. A incidência de fibrilação atrial pós-operatória em ambos os grupos foi semelhante, com nenhuma diferença significativa sendo identificado [n=20 (20%); n=18 (18%), P=0,718; respectivamente]. Não houve mortalidade em ambos os grupos durante o estudo. A necessidade de agente inotrópico em UTI foi semelhante nos dois grupos [n=12 pessoas (12%), n=18 (18%), P=0,32]. Conclusão: Nós comparamos a eficácia do nebivolol e metoprolol na diminuição da incidência de fibrilação atrial no pós-operatório, e verificamos que nebivolol foi tão eficaz como metoprolol na prevenção de fibrilação atrial no pós-operatório em pacientes. Nebivolol pode ser a droga de escolha devido aos seus efeitos, especialmente depois da cirurgia revascularização do miocárdio. .

Efectividad y seguridad del metoprolol succinato en pacientes con taquiarritmias supraventriculares / Effectiveness and safety of metoprolol succinate in patients with supraventricular tachyarrhythmias

Introducción: Se define como arritmia cardiaca a cualquier ritmo diferente al sinusal en presencia de un sistema de conducción atrioventricular normal y como taquiarritmia, a los ritmos cardiacos anormales con frecuencia ventricular mayor a 100 por minuto. Las taquiarritmias supraventriculares (TSV) son aquellas cuyo sitio de formación del impulso se origina por encima de la bifurcación del haz de His; pueden ser repetitivas, persistentes y algunas veces poner en riesgo la vida. Objetivo: Evaluar la evidencia científica sobre los beneficios y riesgos del uso de metoprolol succinato en el tratamiento de pacientes con TSV como uno de los criterios para informar la toma de decisiones relacionada con la posible inclusión de tecnologías en el Plan Obligatorio de Salud, en el marco de su actualización ordinaria para el año 2015. Metodología: Se buscaron revisiones sistemáticas y estudios primarios en los que se hubiera evaluado el uso de metoprolol succinato para evitar episodios de una TSV o para controlar la frecuencia ventricular en el caso de la fibrilación y el flutter auricular. El comparador podía ser placebo, cualquier otro betabloqueador (incluso el metoprolol tartrato) o calcioantagonistas no dihidropiridínicos (verapamilo o diltiazem). No se restringió por fecha de publicación y se buscaron estudios en inglés o español. Resultados: No se encontraron revisiones sistemáticas ni estudios primarios de buena calidad diseñados específicamente para evaluar el impacto del metoprolol succinato sobre los desenlaces clínicamente importantes en pacientes con TSV. Evidencia de baja calidad demostró que en pacientes con FA y falla cardiaca sistólica el uso de metoprolol succinato no disminuye la mortalidad ni las hospitalizaciones y tampoco mejora la calidad de vida. En pacientes con falla cardiaca sistólica en ritmo sinusal, el uso del medicamento succinato se asoció con una disminución en la incidencia de FA. Evidencia de moderada calidad demostró que en pacientes con FA persistente el uso de metoprolol succinato retrasa el tiempo hasta la recaída después de una cardioversión exitosa. Evidencia de muy baja calidad demostró que en pacientes con taquicardia sinusal inapropiada el metoprolol succinato es tan efectivo como la ivabradina para disminuir la frecuencia cardiaca en reposo. Conclusiones: Se necesitan estudios de buena calidad metodológica diseñados específicamente para evaluar la efectividad del metoprolol succinato sobre desenlaces clínicamente importantes en pacientes con TSV.(AU)

Efeitos do metoprolol em modelo experimental de choque séptico / Effects of metoprolol in experimental model of septic shock

O uso de fármacos cardiovasculares tem aumentado consideravelmente nos últimos anos, incluindo o uso de beta-bloqueadores como o metoprolol. E embora estudos experimentais e clínicos tenham demonstrado benefícios na utilização desta classe de fármacos em pacientes sépticos, o bloqueio de receptores beta-adrenérgicos continua sendo contraditório, especialmente no choque séptico. Vinte fêmeas suínas nas quais o choque séptico foi induzido através da infusão intravenosa de Escherichia coli (6x109 UFC/kg em duas horas), foram randomicamente distribuídas (n=10 por grupo) em um grupo Metoprolol (GM; 214.2 ?g/kg de metoprol infundido em 45 minutos) ou grupo Controle (GC), o qual recebeu um volume correspondente de solução salina. Os parâmetros hemodinâmicos e de oxigenação foram avaliados no momento basal (TB), T30, T60, T120, T240 e T360 minutos. Amostras de sangue foram colhidas ainda em TB, T120 e T360 e armazenadas para posterior mensuração da concentração sérica de citocinas e marcadores cardíacos. Durante este período utilizou-se um protocolo de ressuscitação com Ringer lactato, norepinefrina (NE) e dobutamina para manutenção da pressão arterial média (PAM) > 65 mmHg, da pressão venosa central (PVC) em 8-12 mmHg e da saturação venosa mista de oxigênio (SvO2) > 65%. Os dados paramétricos foram analisados utilizando ANOVA de duas vias para medidas repetidas, seguidas por Tukey quando necessário, enquanto para os dados não paramétricos utilizaram-se os testes de Kruskall-Wallis e Mann-Whitney. A quantidade de fluido, NE e dobutamina foi analisada pelo teste t de Student, e a análise de sobrevivência foi realizada utilizando o Kaplan-Meier log-rank test. Exceto por um valor mais elevado do índice de resistência vascular sistêmica (IRVS) em T240 (p=0,02) nos animais tratados com metoprolol, todos os parâmetros analisados neste estudo apresentaram um comportamento similar em ambos os grupos. Nenhuma diferença foi observada também em relação ao volume total de fluido...

The use of cardiovascular drugs considerably increased in recent years, including the use of ?-blockers, such as metoprolol. And although experimental and clinical studies had demonstrated benefits on the administration of these drugs in septic patients, the ?-blockade is still contradictory, especially in the septic shock. Twenty female pigs in which septic shock was induced through intravenous E. coli infusion (6x109 c.f.u/kg in 2h) were randomly assigned (n=10 per group) to the Metoprolol group (214.2 ?g kg-1 of metoprol infused in 45 minutes) or Control group, which received a correspondent volume of normal saline. Hemodynamic and oxygenation parameters were then evaluated at baseline (TB), T30, T60, T120, T240 and T360 minutes. Blood samples were collected at TB, T120 and T360 for posterior mensuration of serum cytokines and cardiac markers. During this period, a resuscitation protocol with lactated Ringer's solution, norepinephrine and dobutamine was used to maintain the mean arterial pressure (MAP) > 65 mmHg, the central venous pressure (CVP) between 8-12 mmHg and the mixed venous oxygen saturation (SvO2) > 65%. Parametric data were compared using the two-way repeated measures ANOVA, followed by the Tukey test when necessary, while the nonparametric data were analyzed with the Kruskall-Wallis and the Mann-Whitney test. The total volume of fluid and total amount of norepinephrine and dobutamine infused were analyzed by the Student's t-test. Survival analysis was performed using Kaplan-Meier log-rank test. Except for the higher values of systemic vascular resistance index (SVRI) at T240 (p=0.02) in the animals that received metoprolol, all the parameters analyzed in this study showed a similar behavior in both groups. No difference was also observed between groups in relation to the total volume of fluid (p=0.914), the total amount of norepinephrine (p=0.069) and dobutamine (p=0.560) infused, and related to the survival rate. Although...

Prognostic analysis of orthostatic intolerance using survival model in children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Orthostatic intolerance (OI) is a common disease at pediatric period which has a serious impact on physical and mental health of children. The purpose of this study was to investigate the effect of related factors on the prognosis of children with OI.</p><p><b>METHODS</b>The subjects were 170 children with OI, including 71 males (41.8%) and 99 females (58.2%) with age from 6 to 17 (12.0±2.6) years. The effect of related factors on the prognosis of children was studied by using univariate analysis. Then, the impact of children's age, symptom score, duration, disease subtype, and treatment on patient's prognosis was studied via analysis of COX proportional conversion model.</p><p><b>RESULTS</b>Among 170 cases, 48 were diagnosed with vasovagal syncope, including 28 cases of vasoinhibitory type, 16 cases of mixed type, and 4 cases of cardioinhibitory type; 115 cases were diagnosed with postural tachycardia syndrome and 7 cases with orthostatic hypotension. By using univariate analysis of Cox regression, the results showed that symptom score had a marked impact on the time of symptoms improvement of children after taking medication (P < 0.05), while other univariates had no impact (P > 0.05). Multivariate analysis using Cox proportional hazards regression model showed that the symptom score at diagnosis had a significant effect on holding time of symptoms improvement of children after taking medication (P < 0.05). Kaplan-Meier curve showed that symptom-free survival was higher in children with symptom score equal to 1 than children with symptom score equal to or greater than 2 during follow-up (P < 0.05).</p><p><b>CONCLUSION</b>Symptom score is an important factor affecting the time of symptom improvement after treatment for children with OI.</p>