Posicionamento de cabo-eletrodo de ventrículo esquerdo na ressincronização cardíaca guiado pela cintilografia miocárdica gated-SPECT* / Positioning of left ventricular lead in cardiac resynchronization guided by gated-SPECT myocardial scintigraphy

A terapia de ressincronização cardíaca representa importante modalidade terapêutica, principalmente para pacientes com insuficiência cardíaca e distúrbios de condução pelo ramo esquerdo. No entanto, a resposta a essa terapia é heterogênea, em virtude dos vários fatores que implicam a dissincronia eletromecânica. O presente relato aborda um caso de sucesso com super-resposta à terapia de ressincronização, na qual o cabo-eletrodo de ventrículo esquerdo foi posicionado de acordo com o sítio de maior retardo determinado pela cintilografia miocárdica com análise de fase gated-SPECT

Cardiac resynchronization therapy represents an important therapeutic modality mainly for patients with heart failure and left bundle branch conduction disorders. However, the response to this therapy is heterogeneous because of the various factors involved in electromechanical dyssynchrony. The present report addresses a successful case with super-response to resynchronization therapy in which the left ventricle electrode was positioned according to the site of greatest delay determined by myocardial scintigraphy with gated-SPECT phase analysis

Comparison of Two Central Venous Pressure Control Strategies to Prevent Atrial Fibrillation After Coronary Artery Bypass Grafting / Comparação de Duas Estratégias de Controle de Pressão Venosa Central na Prevenção de Fibrilação Atrial em Pós-Operatório de Revascularização do Miocárdio

Abstract Background: Atrial fibrillation (AF) takes place in 10-40% of patients undergoing coronary artery bypass grafting (CABG), and increases cardiovascular mortality. Enlargement of atrial chambers is associated with increased AF incidence, so patients with higher central venous pressure (CVP) are expected to have larger atrial distension, which increases AF incidence. Objective: To compare post-CABG AF incidence, following two CVP control strategies. Methods: Interventional, randomized, controlled clinical study. The sample comprised 140 patients undergoing CABG between 2011 and 2015. They were randomized into two groups, G15 and G20, with CVP maintained ≤ 15 cmH2O and ≤ 20 cmH2O, respectively. Results: 70 patients were included in each group. The AF incidence in G15 was 8.57%, and in G20, 22.86%, with absolute risk reduction of 14.28%, and number needed to treat (NNT) of 7 (p = 0.03). Mortality (G15 = 5.71%; G20 = 11.42%; p = 0.07), hospital length of stay (G15 = 7.14 days; G20 = 8.21 days; p = 0.36), number of grafts (median: G15 = 3, G2 = 2; p = 0.22) and cardiopulmonary bypass use (G15 = 67.10%; G20 = 55.70%; p = 0.22) were statistically similar. Age (p = 0.04) and hospital length of stay (p = 0.001) were significantly higher in patients who developed AF in both groups. Conclusion: Keeping CVP low in the first 72 post-CABG hours reduces the relative risk of AF, and may be useful to prevent AF after CABG.

Resumo Fundamento: A fibrilação atrial (FA) ocorre em 10-40% dos pacientes submetidos a cirurgia de revascularização miocárdica (RM), e eleva a mortalidade cardiovascular. Como o aumento dos átrios está associado ao aumento da incidência de FA, espera-se que pacientes com pressão venosa central (PVC) mais alta tenham maior distensão atrial, o que eleva a incidência dessa arritmia. Objetivo: Comparar a incidência de FA em pós-operatório de RM, seguindo duas estratégias de controle de PVC. Métodos: Estudo clínico randomizado controlado intervencionista. A amostra foi composta por 140 pacientes submetidos a RM entre 2011 e 2015. Os pacientes foram randomizados em dois grupos, G15 e G20, mantidos com PVC máxima de 15 cmH2O e 20 cmH2O, respectivamente. Resultados: Foram incluídos 70 pacientes em cada grupo. A incidência da arritmia em G15 foi de 8,57% e, no G20, de 22,86%, com redução de risco absoluto de 14,28% e número necessário para tratar (NNT) de 7 (p = 0,03). Mortalidade (G15 = 5,71%; G20 = 11,42%; p = 0,07), tempo de internamento (G15 = 7,14 dias; G20 = 8,21 dias; p = 0,36), número de enxertos (medianas: G15 = 3, G2 = 2; p = 0,22) e uso de circulação extracorpórea (G15 = 67,10%; G20 = 55,70%; p = 0,22) mostraram-se estatisticamente semelhantes. A idade (p = 0,04) e o tempo de internamento (p = 0,001) foram significativamente maiores nos pacientes que desenvolveram FA nos dois grupos. Conclusão: Manter a PVC com valores mais baixos nas primeiras 72h após a cirurgia de RM reduz o risco relativo de FA e pode ser uma ferramenta útil na prevenção da FA após RM.

Cardiomiopatia Chagásica crônica - diagnóstico e tratamento / Chronic Chagas Cardiomyopathy - diagnosis and treatment

O diagnóstico de cardiomiopatia chagásica crônica deve ser considerado em todo paciente proveniente de áreas endêmicas, que apresente história de doença cardíaca e anormalidades no exame cardiológico, na vigência de duas reações sorológicas positivas (ELISA, imunofluorescência indireta ou hemaglutinação indireta). O ECG convencional e o ecocardiograma transtorácico são fundamentais para revelar a presença de cardiomiopatia subjacente. O tratamento da cardiomiopatia da doença de Chagas deve contemplar as diferentes formas de apresentação da moléstia ­ dor precordial, tromboembolismo, arritmias cardíacas, morte súbita e insuficiência cardíaca crônica (ICC). A dor precordial deve ser tratada com betabloqueadores, antagonistas do cálcio ou nitratos. O tratamento do tromboembolismo deve ser oferecido para os pacientes com alto risco de desenvolver o fenômeno, ou seja, que apresentam fibrilação atrial, trombose mural, tromboembolismo prévio e aqueles com o aneurisma de ponta do VE. Pacientes com taquicardia ventricular sustentada e aqueles recuperados de morte súbita devem receber implante de desfibrilador-cardioversor para a prevenção secundária de morte súbita cardíaca. O tratamento da ICC deve ser semelhante ao preconizado para a ICC de etiologia não chagásica, visto que a fisiopatologia é semelhante, contemplando-se o uso de mineralocorticoides, betabloqueadores, antagonistas da enzima conversora de angiotensinogênio em angiotensina e diuréticos. A digoxina deve ser usada com cautela nesses pacientes, preferencialmente com monitoração de níveis séricos. A terapia de ressincronização cardíaca parece ser promissora nos pacientes com tratamento medicamentoso otimizado. Na ICC terminal, o transplante cardíaco é opção terapêutica segura, tendo em vista os resultados, no mínimo, semelhantes aos observados em pacientes não chagásicos

The diagnosis of chronic Chagas cardiomyopathy should be considered in all patients from endemic areas, presenting history of heart disease and abnormalities in the cardiac examination, in the presence of two positive serologic reactions (ELISA, indirect immunofluorescence, or indirect hemagglutination). The conventional ECG and the transthoracic echocardiography are crucial to reveal the presence of underlying cardiomyopathy. The treatment of Chagas cardiomyopathy should address the different forms of the disease ­ precordial chest pain, thromboembolism, cardiac arrhythmias, sudden death, and chronic heart failure (CHF). Precordial chest pain should be treated with beta-blockers, calcium antagonists, or nitrates. The treatment of thromboembolism should be given to patients at high risk of developing the condition, i.e., that have atrial fibrillation, mural thrombosis, previous thromboembolism, and left ventricular apical aneurysm. Patients with sustained ventricular tachycardia and those with previous cardiac arrest should receive implantable cardioverter-defibrillator for secondary prevention of sudden cardiac death. The treatment of CHF is similar to that recommended to non-Chagas disease heart failure, inasmuch as the pathophysiology is similar, consisting of mineralocorticoids, beta-blockers, angiotensin converting enzyme inhibitors, and diuretics. Digoxin should be used with caution in such patients, preferentially with monitoring of serum levels. Cardiac resynchronization therapy seems promising in patients on optimized medical therapy. In end-stage CHF, heart transplantation is a safe therapeutic option, as the results are at least similar to those found in non-Chagas disease patients

Diuretic effect of alkaloids fraction extracted from Selaginella lepidophylla (Hook. et Grev.) Spring / Efecto diurético de la fracción con contenido de alcaloides extraída deSelaginella lepidophylla (Hook. et Grev.) Spring

The aerial parts of Selaginella lepidophylla (Hook. et Grev.) Spring, are used in Mexican folk medicine to treat renal diseases. The aim of this study was to measure the diuretic response of an aqueous extract (200 mg/kg) and alkaloids fraction at different doses (10, 40 y 100 mg/kg) of this plant and compare it with that induced by furosemide (4 mg/kg). Extract, alkaloids fraction, furosemide and vehicle were administered orally to adult rats and the effects in sodium, potassium and water balance were measured. The extract, the alkaloids fraction and the furosemide produced important and significant increments in urinary excretion of sodium, potassium and water with respect to control group. This increment was dose dependent of the alkaloids fraction, the highest dose produced a major effect. Potassium excretion increased but it was less than the one induced by furosemide. These results suggest that the aqueous extract and rich fraction in alkaloids from S. lepidophylla induce diuretic response.

Las partes aéreas de Selaginella lepidophylla (Hook. et Grev.) Spring, son usadas en la medicina tradicional mexicana para tratar enfermedades renales. El objetivo del estudio fue medir la respuesta diurética de un extracto acuoso (200 mg/kg) y de diferentes dosis de la fracción de alcaloides (10, 40 y 100 mg/kg) de esta planta y compararla con la inducida por furosemida (4 mg/kg). El extracto, la fracción de alcaloides, la furosemida y el vehículo fueron administrados por vía oral a ratas adultas y se midieron los efectos en el balance de sodio, potasio e hídrico. El extracto, la fracción de alcaloides y la furosemida produjeron importantes y significativos incrementos en la excreción urinaria de sodio, potasio y agua con respecto al grupo testigo. Este incremento fue dependiente de la dosis de la fracción de alcaloides, la dosis más alta produjo el mayor efecto. El incremento en la excreción de potasio fue menor al de furosemida. Los resultados sugieren que el extracto acuoso y la fracción rica en alcaloides de S. lepidophylla inducen una respuesta diurética.

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

[ effect of concomitant administration of furosemide and salbutamol on spirometry parameters in persistent asthma]

Considering the effectiveness of nebulized furosemide in asthma crisis that were non-responsive to the inhalational beta-agonists, this study aimed to examine the effect of concomitant administration of furosemide [10 mg] and nebulized salbutamol [2.5 mg] on spirometry parameters in persistent asthma. In this clinical trial, 53 patients [age, 18-75 years] with a 6-months history of persistent asthma were randomly allocated to two groups, the salbutamol [n=27] and salbutamol + furosemide [n=26] groups. Participants in each group were classified into the mild, moderate and severe persistent asthma on the basis of FEV1. Participants were administered salbutamol or salbutamol + furosemide, and then the spirometry parameters were recorded 15 minutes after the completion of nebulization treatment. Before and after the treatment, mean and standard deviation of the spirometry parameters and their changes were calculated. Results showed no significant difference regarding the mean percentage change for FEV1 in the salbutamol [27.5%] and salbutamol + furosemide groups [25.83%] after the treatment [P=0.72]. Moreover, no significant difference was seen between the two groups regarding the mean percentage changes in other parameters after the treatment [FVC, FEV1, PEF, MMEF, FEV1/FVC, P>0.25]. Concomitant administration of furosemide and salbutamol has no advantage over salbutamol in normalizing the spirometry parameters of persistent asthma

Resolution of Macular Edema after Systemic Treatment with Furosemide

We report two cases of macular edema treated with the oral administration of furosemide. The first case presented here was a 78-year-old male patient with visual disturbance of the left eye. He had been taking an oral agent for diabetes and had chronic renal failure for 7 years. From 10 days prior to the visit, he had visual disturbance of the left eye accompanied by systemic edema. There were no specific findings in the anterior segment, but sub-retinal fluid was observed in the left fundus. Macular edema was observed on fluorescein angiography and optical coherence tomography; therefore, the oral administration of furosemide was initiated. After seven days, the sub-retinal fluid disappeared. The second case was a 43-year-old female patient with visual disturbance of the left eye who had been taking hypoglycemic agents for diabetes for 13 years. There were no specific findings in the anterior segment, but flame-shaped retinal hemorrhages were scattered over both posterior poles, neovascularization was observed in the left eye, and, of particular note, sub-retinal fluid was detected in the macula of the left eye. Macular edema was also observed on fluorescein angiography and optical coherence tomography, and oral administration of furosemide was initiated. After 3 weeks, the macular edema had significantly decreased.

Efeito da associação de furosemida e fenilbutazona sobre variáveis hidroeletrolíticas de cavalos antes e após a corrida / The effect of furosemide and phenylbutazone association on the fluid and electrolyte characteristics of horses before and after a race

Verificaram-se os efeitos da associação de furosemida e fenilbutazona sobre variáveis hidroeletrolíticas de cavalos antes e após a corrida. Dezenove equinos foram distribuídos em três grupos, de acordo com os protocolos de tratamento. O primeiro grupo, de cinco animais, não recebeu medicação (grupo-controle); o segundo grupo, de sete animais, foi tratado com furosemida, na dose de 1mg/kg, por via intramuscular, até quatro horas antes do páreo; o terceiro, de sete animais, recebeu furosemida, por via intramuscular, e fenilbutazona, por via intravenosa, nas doses de 1,0 e 4,4mg/kg, respectivamente, até quatro horas antes da corrida. Amostras de sangue foram colhidas antes, imediatamente após e duas horas após o páreo, para avaliação da osmolalidade plasmática e das concentrações plasmáticas de sódio, potássio e cloreto. A utilização de furosemida e da associação furosemida e fenilbutazona até 4h antes dos páreos nas dosagens descritas alterou (P<0,05) a osmolalidade plasmática dos equinos, mas não alterou (P>0,05) as concentrações de sódio, potássio e cloreto. Os páreos alteraram de forma fisiológica a osmolalidade plasmática e a concentração sanguínea de K+ devido ao exercício de alta intensidade.

The objective of this study was to verify the effects of furosemide and phenylbutazone association on fluid and electrolyte balance characteristics of horses before and after a race. Nineteen horses were divided into three groups according to treatment protocols. The first group (five animals - control) was not medicated. A second group (seven animals) was treated with furosemide (1mg/kg, intramuscular up to four hours before the race). A third group (seven animals) received furosemide (1mg/kg) and phenylbutazone (4.4mg/kg), both intramuscular, up to four hours before race. Blood samples were collected before, immediately after and two hours after a race to evaluate the plasma osmolality and sodium, potassium and chloride concentrations. The use of furosemide and furosemide plus phenylbutazone up to four hours before the race altered (P<0.05) the plasma osmolality but did not change (P>0.05) the sodium, potassium and chloride concentrations. It was not possible to determine an antagonist effect of phenylbutazone on furosemide, based on fluid and electrolyte balance. Due to the high intensity exercise, the increase in plasma osmolality and potassium concentration was attributed to the race effect.

Avaliação do efeito da partição de comprimidos de furosemida sobre a uniformidade da dose / Influence of tablet splitting on dose uniformity

Buscando avaliar a uniformidade da dose unitária de comprimidos submetidos ao procedimento de partição, este trabalho avaliou a dureza, friabilidade, variação de peso e uniformidade de conteúdo em quatro amostras de comprimidos de furosemida de 40 mg, obtidas de diferentes fornecedores. Todas as amostras estudadas atendiam às especificações oficiais antes de serem submetidas ao procedimento de partição; porém, após serem partidas, o teor de fármaco nas metades apresentou excessiva variação, mostrando que esse procedimento pode ser terapeuticamente desaconselhável.

In order to assess the uniformity of the dose of active ingredient in the halves of tablets subjected to splitting, the hardness, friability, weight variability and uniformity of content were studied in four samples of 40 mg tablets of furosemide obtained on the Brazilian market, both whole and split into two parts. All the tablets complied with the official specifications before splitting, but, after this procedure, the drug content in the halves showed excessive variation, indicating that this procedure is inadvisable.

A comparison between sphygmomanometer-based and ambulatory blood pressure monitoring in acute salt loading and depletion protocol

INTRODUCTION: Ambulatory blood pressure monitors have been used in salt loading and depletion protocols. However, the agreement between measurements made using ambulatory blood pressure monitors and those made with the sphygmomanometer has not been evaluated. OBJECTIVE: The objective of this study was to compare the concordance of the two methods of blood pressure measurements in protocols of acute salt loading and depletion. METHOD: Systolic blood pressure was measured using a sphygmomanometer at the completion of salt infusion (2 L NaCl 0.9 percent, 4 h) and salt depletion (furosemide, 120mg/day, p.o.) in 18 volunteers. Using the Pearson correlation coefficient (ρ), these readings were compared with the mean systolic blood pressure measured using the ambulatory blood pressure monitoring device during the following periods: 4 h of saline infusion and 12 h of salt depletion; 4 h of saline infusion and the last 6 h of salt depletion; 12 h of salt loading and the last 6 h of depletion; 12 h of salt loading and 12 h of depletion. Salt sensitivity was defined by a difference in the systolic blood pressure between salt loading and salt depletion greater than 10 mmHg when measured with the sphygmomanometer, and the Kappa analysis of concordance (K) was used with a significance level of P<0.05. RESULTS: Only the blood pressure readings obtained using the ambulatory blood pressure device during 4 h of intravenous NaCl and during 12 h of salt depletion showed a high correlation with the variation in the systolic blood pressure measured by the sphygmomanometer, with a full agreement with the salt sensitivity classification (p = 0.71; P = 0.001 and K=1). CONCLUSION: In acute salt loading and depletion protocols, an ambulatory blood pressure monitoring device should be used to record the blood pressure during the 4-h interval of salt infusion and 12-h interval of salt depletion.

Alteración del sodio y potasio en pacientes hospitalizados por insuficiencia cardíaca / Alteration of sodium and potassium levels in patients hospitalized for heart failure

La insuficiencia cardíaca es un síndrome ocasionado por múltiples factores y va produciendo un proceso de remodelado ventricular. Es un verdadero problema de salud pública que incrementa el número de hospitalizaciones. Los diuréticos siguen siendo útiles en el tratamiento, aún así se producen alteraciones de los electrólitos que pueden ocasionar arritmias, empeoramiento de la insuficiencia cardíaca y disminución de la fracción de eyección. Este trabajo evalúa la alteración del sodio y potasio en pacientes hospitalizados por este síndrome. Se revisaron las historias de pacientes con insuficiencia cardíaca ingresados al servicio de Cardiología, registrando datos en base a un protocolo. Se revisaron 33 historias de las cuales 11 pacientes eran mujeres y 22 eran hombres, con un promedio de edad de 72,64 y 71,52 años respectivamente. Días de hospitalización promedio de 14,91 días. Todos los pacientes tenían dieta hiposódica excepto uno debido a diarrea. El 57,6% tenían una sola patología y el resto dos o tres. La hipertensión arterial es la patología más frecuente en un 81,8%, seguido de cardiopatía isquémica en un 30,3%. Recibieron tres diuréticos (furosemida, espirolactona, hidroclorotiazida) el 48,5% de los pacientes y dos diuréticos el 48,5%. El 51,5% de los pacientes tenían potasio bajo y el 57,6% sodio bajo. En un 50% de los pacientes se encuentra que el potasio y sodio están bajos que se relaciona con el uso de diuréticos y una dieta hiposódica. Habría que considerar el uso de suplemento de potasio en estos casos.

Heart failure a syndrome caused by multiple factors engenders a process of ventricular remodeling. It is an enormous public health problem, with an increasing number of hospitalizations. Diuretics, still useful for treatment, produce electrolyte abnormalities can cause arrhythmias, worsening heart failure and larger reduction in the ejection fraction. This study evaluated the alteration of sodium and potassium levels in patients hospitalized with this syndrome. We reviewed the charts of patients with heart failure admitted to the cardiology service, recording data with the use of a standardized form. We reviewed 33 records for 11 women and 22 men with a mean age of 72.64 and 71.52 years respectively. The average number of days of hospitalization was 14.91 days. All patients had a low sodium diet except one because of diarrhea. A single pathology was present in 57.6% with the rest having two or three. Hypertensión was the most frequent pathology in 81.8% , followed by ischemic heart disease in 30.3%. Three diuretics (furosemide, spironolactone, hydrochlorothiazide) were used in 48.5% of patients and two diuretics in 48.5%. In 51.5 of patients there was low potassium and in 57.6% low sodium. Potassium and sodium were low in 50% of patients, which was associated with the use of diuretics and a low salt diet. Potassium supplements should be considered in these cases.

Influência do veículo na eficácia da reposição de potássio em ratos hipocalêmicos / Vehicle influence on potassium replacement effectiveness in hypokalemic rats

INTRODUÇÃO: Pacientes após cirurgia cardíaca são comumente tratados com diuréticos para controle de volume plasmático. A preocupação de distúrbios hipocalêmicos em adultos antes, durante ou após a cirurgia já foi ressaltada anteriormente, visto o risco de arritmias cardíacas. Clinicamente, a diluição da solução de potássio (K+) para administração por via intravenosa, em situações que requerem a sua reposição é realizada utilizando-se soro fisiológico (SF) ao invés de soro glicosado 5 por cento (SG5 por cento), possivelmente em vista de poder ocorrer estimulação da secreção de insulina, que interferiria sobre a qualidade da reposição de K+. Porém, não está comprovado experimentalmente se o SF e SG5 por cento poderiam realmente interferir na qualidade da reposição de potássio em ratos com hipocalemia. OBJETIVO: Analisar a influência da reposição de K+ diluído em diferentes veículos sobre as concentrações plasmáticas de K+([K+]p) em ratos submetidos a hipocalemia induzida por furosemida. MÉTODOS: Ratos Wistar adultos foram divididos em quatro grupos: K++SF, K++SG, SF e SG. Foi realizada a canulação da veia jugular para reposição e da veia femoral para coleta de sangue. O diurético furosemida na dose de 50mg/kg foi usado para induzir hipocalemia, foi analisado nível plasmático de potássio 24 h antes da injeção de furosemida, 24 h pós-indução e 30 minutos pós-reposição. RESULTADOS: Os níveis da [K+] pós-injeção de furosemida sofreram redução, comparado aos valores basais (pré-furosemida) em todos os grupos. Entretanto, os níveis [K+] retornaram aos valores basais tanto nos grupos que receberam K++SF ou K++SG, o que não foi observado nos grupos que receberam apenas SF e SG. Quanto ao Na+ plasmático, somente o grupo K+SF apresentou aumento após reposição. CONCLUSÃO: A reposição de K+ diluído tanto em SF quanto SG parece não afetar a qualidade da reposição de K+ plasmático em ratos

INTRODUCTION: Patients who undergo cardiac surgery are commonly treated with diuretic therapy for the management of volume overload. The concern of hypokalemia important in the adult population submitted to cardiac surgery has been described. Intravenous potassium (K+) replacement dilution is only recommended with sodium chloride 0.9 percent solution (SF0.9 percent), likely due to the putative effects of glucose solution 5 percent (SG5 percent) on insulin secretion, which influence K+ replacement quality. However, it is not yet experimentally proved the influence of SF0.9 percent and SG5 percent on K+ replacement quality. Objectives: To evaluate the effects of different vehicles of K+ replacement on blood K+ levels in furosemide hypokalemic rats. METHODS: Male Wistar rats divided into four groups: K+SF, K+SG, SF and SG. Jugular vein cannulation for K+ replacement and femoral vein cannulation for blood analysis. Furosemide (50mg/kg) to induce hypokalemia. We prepared the following solutions: vehicle 1.6mL (SF0.9 percent or SG5 percent) + 0.4 mL de K+ (19.1 percent) and for control groups only vehicle 2 mL. Furosemide (50 mg/kg) was used to induce hypokalaemia, it was analyzed potassium plasmatic levels 24 hours before furosemide injection, 24 hours after furosemide injection and 30 minutes after post-replacement. RESULTS: There was no significative difference in blood K+ levels before furosemide administration, after hypokalemic induction and after K+ replacement among all groups. Only SF+K presented blood Na+ levels increaseafter K+ replacement (P<0.05). CONCLUSION: K+ replacement in different vehicles did not affect blood K+ levels in rats

Influência da terapia com espironolactona sobre níveis sangüíneos de tiamina em pacientes com insuficiência cardíaca / Influence of spironolactone therapy on thiamine blood levels in patients with heart failure

FUNDAMENTO: Estudos do manejo não-farmacológico da insuficiência cardíaca (IC) têm sido muito escassos. A importância de micronutrientes como tiamina há muito é conhecida, uma vez que sua deficiência está associada com o desenvolvimento de IC de alto débito. OBJETIVO: Nós estudamos a relação entre adicionar à inibição da ECA uma supressão adicional da aldosterona com espironolactona e níveis sangüíneos de tiamina (pmol/ml). MÉTODOS: Um total de 22 pacientes (pc) com IC (classes III/IV da NYHA) foi dividido em dois grupos [grupo I - espironolactona 25mg/dia (n=11) e grupo II - sem espironolactona (n=11)]. Determinamos os níveis de tiamina pelo uso da atividade da transcetolase eritrocitária. Os grupos foram comparados com relação à ingesta alimentar, demografia, doses de furosemida e níveis sangüíneos de tiamina, usando os testes de Mann-Whitney e t de Student. Analisamos as proporções com testes de qui-quadrado e de Kruskal-Wallis para associarmos a tiamina com fatores demográficos e usamos as doses de furosemida como variáveis dependentes. RESULTADOS: Os grupos I e II eram similares em relação à ingesta alimentar, doses diárias de furosemida (110,9±30,2 e 105,5±26,9 mg, respectivamente; p>0,05), demografia (etiologia, idade, hipertensão, diabete, tabagismo, abuso de álcool, dislipidemia e tratamento adjuvante da IC com drogas). Os pacientes do grupo I mostraram níveis de tiamina significativamente superiores, comparados com aqueles do grupo II (277,2±89,8 e 154,7±35,7, respectivamente) (p<0,001). Nenhuma das variáveis dependentes citadas acima estava associada com a tiamina. CONCLUSÃO: Em uma coorte de pacientes ambulatoriais com IC tratados com alta dose de diuréticos de alça, o uso de espironolactona está associado com níveis sangüíneos superiores de tiamina. A importância deste achado ainda deverá ser estabelecida por estudos futuros com desenho prospectivo e amostras maiores.

BACKGROUND: The nonpharmacological management of heart failure (HF) has been understudied. The importance of micronutrients such as thiamine has long been known since its deficiency is associated with the development of high-output HF. OBJECTIVE: We studied the relationship between adding to ACE inhibition further aldosterone suppression with spironolactone and thiamine blood levels (pmol/ml). METHODS: A total of 22 patients (pts) with HF (NYHA III/IV) were divided in two groups [group I-spironolactone 25mg/qd (n=11) and group II - no spironolactone (n=11)]. Thiamine levels were determined using the erythrocyte transketolase activity. The groups were compared regarding food intake, demographics, furosemide doses and thiamine blood levels using Mann-Whitney and student's T-test. The proportions were analyzed with Chi-square and Kruskal-Wallis tests to associate thiamine with demographics and furosemide doses as dependent variables. RESULTS: Group I and II were similar regarding food intake, daily furosemide doses (110.9±30.2 and 105.5±26.9 mg, respectively; p>0.05), demographics (etiology, age, hypertension, diabetes, smoking, alcohol abuse, dyslipidemia and adjuvant drug HF treatment). Pts in group I showed significantly higher thiamine levels when compared to pts in group II (277.2±89.8 and 154.7±35.7, respectively) (p<0.001). None of the dependent variables cited above were associated with thiamine. CONCLUSION: In a cohort of ambulatory HF patients on high dose of loop diuretics, the use of spironolactone is associated with higher thiamine blood levels. The significance of this finding remains to be established by future studies with prospective design and larger sample sizes.

Influência da terapia com diuréticos nos níveis séricos de tiamina em pacientes com insuficiência cardíaca / Influence of diuretic therapy on thiamin blood levels in patients with heart failure

Fundamento - A importância de micronutrientes como tiamina há muito é conhecida, visto que sua deficiência associa-se com insuficiência cardíaca (IC) de alto débito. Vários trabalhos mostram a influência dos diuréticos nos níveis de tiamina. Objetivos - Avaliar se o uso de furosemida isolada ou associada a espironolactona (espiro) determina níveis de tiamina diferentes em pacientes (pc) com IC. Verificar se a tiamina é influenciada por fatores nutricionais, comorbidades e outros fármacos. Métodos - Estudo em duas etapas: Estudo 1 - análise transversal (uso prévio de furosemida isoladamente ou em associação com espiro) de 22 pc com IC (classes III/IV da NYHA) divididos em: grupo I - com epiro (n=11) e grupo II - sem espiro (n=11); Estudo 2 - ensaio clínico randomizado, aberto, com três grupos paralelos de 53 pc com IC divididos em grupo "sem diuréticos" (n=15), "com diurético" (n=15) (uso de furosemida até o dia 90 e depois associar espiro até o dia 180) e "com espiro" (n=23) (usar furosemida e espiro desde a visita inicial até o dia 180). Os pc realizaram três visitas: inicial, em 90 dias e 180 dias, sendo coletadas amostras de sangue para tiamina e outros exames, assim como análise clínica. Determinamos os níveis de tiamina por recombinação de apoenzima e por cromatografia líquida de alta performance. Utilizamos testes t de Student, qui-quadrado, Mann-Whitney, Kruskal-Wallis, Spearman e como a variância foi cerca de três vezes maior que a estimada, usamos a simulação robusta de Monte Carlo. Resultados: no estudo 1, os grupos I e II eram similares em relação à ingesta alimentar, doses diárias de furosemida (I=110,9 +- 30,2 vs II=105,5 +-26,9mg; p>0,05) e dados demográficos. Os pacientes do grupo I mostraram níveis maiores de tiamina (277,2+-89,8), comparados aos do grupo II (154,7+-35,7) (p<0,001). Nenhuma outra variável esteve associada com a tiamina. No estudo 2, os grupos também eram semelhantes quanto às características clínicas e laboratoriais...

Background: The importance of micronutrients such as thiamine known since its deficiency is associated with the development of high-output heart failure (HF). Several studies show the influence of diuretic therapy in thiamine blood levels. Objectives: assess whether the use of furosemide alone or in combination with spironolactone (spiro) can determine different thiamine blood levels in patients (pt) with HF. To determinat whether thiamine blood levels were influenced by nutritional factors, comorbidities and other drugs. Methods: Study 1 - cross-sectional analysis (previous use of furosemide alone or with spiro) of 22 HF pt (NYha class III/IV) divided in two groups: I - with spiro (n=11) and II - without spiro (n=11); Study 2 - randomized, open-label, with three parallel groups of 53 HF pt divided into group "without diuretics" (n=15), "with diuretic" (n=15) (use of furosemide until day 90 and then adding spiro from day 90 until day 180) and "with spiro" (n=23) (using furosemide and spiro through all study). Patients were scheduled to three visits: day 0, day 90 and day 180, and blood samples were collected for thiamine and other tests, as well as clinical analysis. Thiamine levels were determined using an apoenzyme recombination method and high-performance liquid chromatography. The tests used were t-Student, chi-square, Mann-Whitney, Kruskal-Wallis, Spearman correlation, and as the variance was about three times higher than estimated, we used a robust Monte Carlo simulation. Results: in study 1, group I and II were similar regarding food intake, daily furosemide doses (I=110.9+-30.2 vs II=105.5+-26.9 mg; p>0.05) and demographics. Pts in group I (277.2+-89.8) showed significantly higher thiamine levels when compared to pts in group II (154.7+-35.7) (p<0.001). No other variables were associated with thiamine. In study 2, the groups were also similar regarding clinical and laboratory assessments. We found no statistical differences in thiamin blood levels...

Technological development of 40mg furosemide tablets: equivalence and bioavaibility study in dogs

Furosemide (40mg) was administered to 20 street dogs, 10 males and 10 females, in two different pharmaceutical forms: (1) compressed furosemide 40mg formulated at the Federal University of Pernambuco (UFPE-tablet), and (2) a commercial formulation with equal bioequivalence produced by the Laboratory for Pharmaceutical Technology of Pernambuco State (LAFEPE), the LAFEPE-furosemide. The study aimed to evaluate the kinetics of dissolution of the UFPE-tablet in order to analyze the behavior of bioavailability of the best formulation for veterinary use. The plasmatic concentrations of furosemide for the determination of parameters of pharmacological kinetics were analyzed by high-performance liquid chromatographic method (HPLC). The in vitro study accomplished through physiochemical analyses demonstrated that the formulas of the furosemide tablets attained the pharmaceutical requirements in agreement with USP 23 and the Brazilian Pharmacopoeia. The evaluation accomplished in dogs with UFPE-tablets given in only dose demonstrated uniformity in blood levels indicating stability in maintenance of the pharmaceutical formulation and efficiency in absorption of the active compound. These values are not significantly different in relation to the 5 percent confidence limit. Regarding maximum concentration (Tmax) time and global bioavaibility assessed by AUC means, there were no considerable differences as well. UFPE-furosemide displayed 743.492µg/mL.h as AUC average value whereas LAFEPE-furosemide had an average of 537.284µg/mL.h.

Furosemida (40mg) foi administrada a 20 cães de rua (cães SRD), 10 machos e 10 fêmeas, em duas formas farmacêuicas distintas: (1) furosemida comprimido 40mg formulada na Universidade Federal de Pernambuco (UFPE-comprimido) e (2) uma formulação comercial bioequivalente produzida pelo Laboratório de Tecnologia Farmacêutica do Estado de Pernambuco (LAFEPE-furosemida). O estudo objetivou avaliar a cinética de dissolução do UFPE-comprimido para analisar o comportamento da liodisponibilidade dos comprimidos buscando a melhor formulação para uso veterinário. As concentrações plasmáticas de furosemida para determinação de parâmetros farmacocinéticos, foram analisadas por cromatografia líquida de alto desempenho (HPLC). O estudo in vitro realizado através de análises físico-químicas demonstrou que as fórmulas dos comprimidos de furosemida preencheram os requisitos farmacêuticos de acordo com USP 23 e a Farmacopéia Brasileira. Avaliações realizadas em cães da formulação UFPE-comprimidos administrados em dose única, demonstrou uma uniformidade nos níveis sangüíneos indicando estabilidade na manutenção da forma farmacêutica e eficiência na absorção do princípio ativo. Estes valores não são significativamente diferentes em relação ao limite de confiança de 5 por cento. Em relação a concentração de máximo (Tmax) e ao tempo de biodisponibilidade global avaliados por meios de AUC, não houve nenhuma diferença considerável. O comprimido UFPE-furosemide exibiu AUC de 743.492µg/mL.h e o LAFEPE-furosemide teve uma média de 537.284µg/mL.h.