Inhibition of diabetes mellitus-induced knee joint injury in rats by a combination of metformin and captopril / Inhibición de la lesión de la articulación de la rodilla inducida por diabetes mellitus en ratas mediante una combinación de metformina y captopril

SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee joint articular cartilage associated with the inhibition of glycemia, dyslipidemia, and inflammation has not been investigated before. Therefore, we induced diabetes in rats using high carbohydrate and fat diets and a single injection of streptozotocin (50 mg/kg). The protective group of rats was pre-treated with combined daily doses of metformin (Met; 200 mg/kg body weight) and captopril (Cap; 150 mg/kg body weight) for 14 days before diabetic induction and continued on metformin and resveratrol until the end of the experiment at week 12. Harvested tissues obtained from knee joints were prepared for basic histology staining with haematoxylin and eosin (H&E) and examined under light microscopy. Representative H&E images showed that OA was developed in the diabetic rats as demonstrated by a profound damage to the knee joints such as irregular eroded and a sharp decrease in the thickness of the articular cartilage surface and abnormal remodeling of the subchondral bone that were substantially ameliorated by Met+Cap. Met+Cap also significantly (p< 0.05) reduced blood levels of glucose, glycated hemoglobin (HbA1c), dyslipidemia, and the inflammatory biomarkers, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) induced by diabetes. In addition, a significant (p≤ 0.0014) correlation between the articular cartilage thickness and the blood levels of glucose, HbA1c, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), and hs-CRP were observed. Thus, we demonstrate that Met+Cap effectively protect the knee joint against injuries induced secondary to diabetes in rats, possibly due to the inhibition of glycemia, dyslipidemia, and biomarkers of inflammation.

RESUMEN: La osteoartritis (OA) es una enfermedad inflamatoria que daña las articulaciones y afecta a millones de per- sonas en todo el mundo. No se han investigado los posibles efectos inhibidores del fármaco antidiabético metformina combinado con captopril, el inhibidor de la enzima convertidora de angiotensina, sobre el daño inducido por la diabetes en el cartílago articular de la articulación de la rodilla asociado con la inhibición de la glucemia, dislipidemia e inflamación. En este estudio fue inducida la diabetes en ratas con dietas altas en carbohidratos y grasas y una sola inyección de estreptozotocina (50 mg / kg). El grupo protector de ratas se pretrató con dosis diarias combinadas de metformina (Met; 200 mg / kg de peso corporal) y captopril (Cap; 150 mg / kg de peso corporal) durante 14 días antes de la inducción diabética. El tratamiento se continuó con metformina y resveratrol hasta el final del experimento en la semana 12. Los tejidos obtenidos de las articulaciones de la rodilla se prepararon para la tinción de histología básica con hematoxilina y eosina (H&E) y se examinaron con microscopía óptica. Imágenes representativas de H&E mostraron que la OA se desarrolló en las ratas diabéticas, como lo evidencia un daño profundo en las articulaciones de la rodilla, como la erosión irregular y una fuerte disminución en el grosor de la superficie del cartílago articular y remodelación anor- mal del hueso subcondral que fueron mejorados sustancialmente por Met + Cap. Met + Cap. También redujo significativamente (p <0.05) los niveles sanguíneos de glucosa, hemoglobina glicosilada (HbA1c), dislipidemia y los biomarcadores inflamatorios, proteína C reactiva de alta sensibilidad (hs-CRP), interleucina-6 (IL-6), y factor de necrosis tumoral alfa (TNF-α) inducido por diabetes. Además, una correlación significativa (p≤ 0,0014) entre el grosor del cartílago articular y los niveles sanguíneos de glucosa, HbA1c, triglicéridos (TG), lipoproteínas-colesterol de baja densidad (LDL- C), lipoproteínas de alta densidad-colesterol (HDL-C) ) y hs-CRP. Así, demostramos que Met + Cap protege eficazmente la articulación de la rodilla contra lesiones inducidas por diabetes en ratas, posiblemente debido a la inhibición de la glicemia, dislipidemia y biomarcadores de inflamación.

Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation

Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.

Consumo y costo de antihipertensivos en Cuba en el período 2003-2013 / Consumption and cost of antihypertensive drugs in Cuba in the 2003-2013 period

Objetivo: describir el patrón de utilización de medicamentos antihipertensivos y su costo entre 2003 y 2013. Método: la información sobre el consumo se obtuvo de la base COMEDICS perteneciente a BIOCUBAFARMA, que contiene las especialidades farmacéuticas facturadas al Sistema Nacional de Salud. El consumo se expresó en dosis diarias definidas (DDD) por 1 000 habitantes y día (DHD). Para el cálculo del costo se utilizó el precio de venta a la población en CUP, vigente en las farmacias comunitarias del país. Resultados: el consumo de antihipertensivos en Cuba muestra un marcado incremento en los últimos 10 años, pasó de 100,2 a 268,0 DHD (167,5 por ciento). Para el conjunto de los antihipertensivos, los costos pasaron de 42,9 a 136,3 millones de CUP, para un incremento de 93 millones (217 por ciento). Para el 2013 los IECA representaron el 53 por ciento del consumo total y el 71 por ciento de los costos. Los diuréticos fue el grupo que mostró una mejor relación entre el consumo y los costos; con 28 por ciento del consumo representaron sólo el 9 por ciento de los costos. La introducción del amlodipino, contrario a lo esperado, no generó una disminución del consumo de la nifedipina. Conclusiones: se produjo en el periodo un cambio del patrón de consumo, que se desplazó hacia medicamentos más costosos como el enalapril, el captopril y el amlodipino, con un aumento del costo del tratamiento de la hipertensión(AU)

Objectives: to describe the pattern of use and the cost of antihypertensive drugs in Cuba from 2003 to 2013. Method: information on drug utilization was obtained from the COMEDICS database of the BIOCUBAFARMA which records the number of packages charged to the National Health System. Consumption data were expressed in defined daily dose (DDD) per 1000 inhabitants per day (DHD). For estimation of costs, the sale price in Cuban pesos for the population in the community pharmacies of the country was used. Results: the consumption of antihypertensive drugs in Cuba has increased remarkably in the last 10 years, from 100.2 to 268.0 DHD (167,5 percent). Overall costs increased from 42,9 to 136,3 million CUP, accounting for 217 percent increase. In 2013, IECA accounted for 71 percent of the costs and 53 percent of the consumption. The diuretics were the group that showed a better relationship between the consumption and the costs, with 28 percent of the consumption, they just represented 9 percent of the costs. Contrary to expectations, the introduction of amlodipine did not generate a decrease in the consumption of the nifedipine. Conclusions: in the period, the consumption patterns changed and moved toward more expensive medications as enalapril, captopril and amlodipine, which means that the cost of hypertension treatment increased(AU)

Avaliação do uso do captopril na fibrose peritoneal induzida em ratos pelo uso de solução de glicose a 4,25% / Evaluation of the use of captopril on peritoneal fibrosis induced in rats by the use of glucose solution 4.25%

INTRODUÇÃO: A Insuficiência Renal Crônica (IRC) tem incidência alarmante neste século. A diálise peritoneal, uma das modalidades de terapia renal pode ter complicações, e entre estas a fibrose peritoneal, que ocorre com o decorrer dos anos nestes pacientes. Sua forma mais grave é a chamada peritonite esclerosante encapsulante, levando à mudança de terapia dialítica. OBJETIVO: Estudar a influência do uso do captopril na fibrose peritoneal induzida em ratos pelo uso de solução de glicose a 4,25 %. MÉTODOS: Estudo prospectivo controlado, em ratos Wistar não urêmicos. Foram estudados 20 animais. Os animais foram submetidos diariamente à punção abdominal, sendo infundida solução de diálise peritoneal com glicose a 4,25% na dose de 10 ml/100 g de peso. Os animais foram divididos em 2 grupos: experimental e controle. O grupo experimental recebeu captopril na dose de 30 mg/kg/dia por gavagem. O grupo controle não recebeu nenhuma droga. Foram acompanhados por 21 e 49 dias. Ao final do período foram submetidos à procedimento cirúrgico para retirada de peritônio parietal e visceral. As amostras obtidas foram analisadas histologicamente, usando-se coloração Hematoxilina - Eosina e Sirius Red, para avaliação do grau de fibrose. RESULTADOS: A análise mostrou que a intensidade da fibrose, a espessura do peritônio e o número de células não atingiram diferença estatisticamente significante entre os grupos experimental e controle. CONCLUSÃO: O estudo mostrou que o uso do captopril não foi capaz de alterar a intensidade da fibrose peritoneal induzida pelo uso de solução de diálise em ratos.

INTRODUCTION: Chronic renal failure has alarming incidence all over the world in this century. Among the modalities of dialytic treatment, peritoneal dialysis has a major spot. This method of dialytictreatment may present complications, and among those is peritoneal fibrosis. It occurs in patients submitted to peritoneal dialysis along years. It's most dangerous form is sclerosing encapsulant peritonitis, wich leads to a need of change in modality and many times lead to death. OBJECTIVE: Study the influence of using captopril on the peritoneal fibrosis induced in rats using solution with glucoses 4.25%. METHODS: Prospective controlled study in 20 non-uremic Wistar rats. The animals received a peritoneal infusion of 10 ml/100g of peritoneal dialysis solution glucose 4.25% on a daily basis. The animals were divided in two groups: experimental and control. The experimental group received captopril 30 mg/kg/d, by a gastric tube. The control group did not receive any drug. The follow-up was 21 and 49 days. At the end, one surgical procedure was performed to get histological samples of visceral and parietal peritoneum. The samples were analyzed using Hematoxylin Eosin and Sirius Red, to evaluate the severity of the fibrosis. RESULTS: The analysis showed that the intensity of the fibrosis, the peritoneal thickness and the cell number in experimental and control groups were not statistically significant different in experimental and control groups. CONCLUSION: Our findings indicate that captopril do not decrease the intensity of fibrosis on the peritoneal membrane that happens on rats on peritoneal dialysis.

Eficacia de la microdosis de captopril en el tratamiento de la hipertensión arterial esencial / Effectiveness of captopril microdosing in the treatment of essential arterial hypertension

Introducción: prescribir una terapéutica adecuada siempre es complejo, más aun cuando los índices de control y la seguridad de los medicamentos no satisfacen los objetivos esperados, la microdosis pudiera convertirse en una alternativa eficaz. Objetivo: evaluar la eficacia de la microdosis de captopril en el tratamiento de la hipertensión arterial esencial. Métodos: se realizó un ensayo clínico fase III, unicéntrico, aleatorizado y controlado, en el Hospital Universitario Manuel Ascunce Domenech, de Camagüey, entre enero de 2007 y diciembre de 2009. Se creó un formulario con las variables: control clinico, grupos etarios, grado hipertensivo, grado de riesgo cardiovascular, dosis mínima necesaria para control. La información obtenida fue sometida a un procesamiento estadístico de análisis en el programa SPSS versión 15.0. Se utilizaron técnicas estadísticas para hallar diferencias entre variables. Resultados: la microdosis de captopril resultó ser más eficaz que las tabletas en el tratamiento a largo plazo de la hipertensión arterial, en particular en pacientes con 60 años y más de edad, en los hipertensos grados II y III y con más alto riesgo, aún con el uso de una dosis menor. Conclusiones: la microdosis de captopril fue eficaz en el tratamiento de la hipertensión arterial esencial, al permitir mejor control clínico con una menor dosis de medicamento

Introduction: prescribing the appropriate therapeutic treatment is always a complex task, particularly when drug control and safety indices do not accomplish the expected goals. In such a context, microdosing could be an effective alternative. Objective: evaluate the effectiveness of captopril microdosing in the treatment of essential arterial hypertension. Methods: aunicenter controlled randomized phase III clinical trial was conducted at Manuel Ascunce Domenech University Hospital in the province of Camagüey from January 2007 to December 2009. A form was prepared which included the following variables: clinical control, age group, hypertension grade, cardiovascular risk grade, minimum dose required for control. The information collected was subjected to statistical processing and analysis with the software SPSS versión 15.0. Statistical techniques were used to find differences between the variables. Results: captopril microdosing was more effective than tablets for the long-term treatment of arterial hypertension, particularly in patients aged 60 and over, grade II and III hypertensives, and higher risk patients, even with the use of a smaller dose. Conclusions: captopril microdosing was found to be effective for the treatment of essential arterial hypertension, allowing a better clinical control with a smaller dose of the medication

Glomerular filtration rate measured by 51Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis (51Cr-EDTA) and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m² in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m² in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m², p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m², p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did...

Left ventricular noncompaction: A cardiomyopathy often mistaken.

Left ventricular noncompaction (LVNC) is a rare genetic cardiomyopathy postulated to be a defect in endomyocardial morphogenesis due to the embryonic arrest of the compaction of myocardial fibers. It could be isolated, without other structural heart defects; or associated with congenital heart defects. It is characterized by prominent ventricular myocardial trabeculations and deep intertrabecular recesses. The clinical manifestations, i.e., heart failure, arrhythmias or thromboembolism, overlap with those of other cardiac disorders. It is often misdiagnosed as restrictive or dilated cardiomyopathy. The high mortality and morbidity associated with it and familial occurrence make diagnosis important. Only 3 pediatric cases have been reported from India. We present 2 cases, that of an 11-year-old girl (familial case) with embolism (documented but rare in children) and atrial flutter (not yet reported), with mother having asymptomatic LVNC; and that of a 4-month-old girl. Both presented with heart failure. The 11-year-old child had sudden death, known to occur in LVNC.

Avaliação do perfil lipídico de pacientes diabéticos e hipertensos tratados com captopril / Evaluation of lipid profile in diabetic and hypertensive patients treated with captopryl

INTRODUÇÃO E JUSTIFICATIVA: Doença arterial coronariana (DAC) é a principal causa mundial de morte em indivíduos adultos, e como importantes fatores de risco tratáveis envolvidos estão o diabetes mellitus (DM), as dislipidemias e a hipertensão arterial sistêmica (HAS). O tratamento com anti-hipertensivos pode provocar alterações indesejáveis no perfil lipídico, atenuando seus efeitos benéficos antiaterogênicos na redução da pressão arterial (PA). OBJETIVO: Avaliar o perfil lipídico de indivíduos diabéticos tipo 2 com hipertensão essencial tratados somente com captopril ou em combinação com outros anti-hipertensivos, procurando evidenciar a melhora no padrão lipídico destes pacientes, levando a efeito protetor. MATERIAL E MÉTODOS: Foram avaliados níveis de colesterol total (CT), colesterol da lipoproteína de alta densidade (HDL-C), colesterol da lipoproteína de baixa densidade (LDL-C) e triglicérides (TG) de 140 pacientes encaminhados ao laboratório de análises clínicas da Universidade do Oeste Paulista (UNOESTE), com idade média de 59,7 ± 10,9 anos, de ambos os sexos, portadores de diabetes tipo 2 e hipertensão. O controle glicêmico foi determinado pela dosagem de hemoglobina glicada (HG). Estes pacientes foram subdivididos de acordo com controle metabólico glicêmico (satisfatório ou comprometido) em dois grupos: tratados somente com captopril (DC) e tratados com combinação captopril e hidroclorotiazida (HCTZ). Dos pacientes com HG < 8,8 por cento (controlado), DC e HCTZ apresentaram respectivamente níveis de CT (210,2 ± 43,7 e 198,3 ± 37,5), HDL (49 ± 10,9 e 49,2 ± 8,7), LDL (126,9 ± 43,3 e 119,8 ± 23,8), TG (181,9 ± 86,4 e 161,2 ± 83,8) e G (151,3 ± 51,4 e 163 ± 66,5), não havendo diferenças significativas entre eles. Já nos pacientes com HG > 11,2 por cento (não-controlado), DC e HCTZ obtiveram respectivamente níveis de CT (214,3 ± 45,9 e 197 ± 49,5), HDL (35,3 ± 20,5 e 41,5 ± 0,7), LDL (121 ± 43,3 e 116,5 ± 38,9), TG (271,5 ± 175,2 ...

INTRODUCTION AND BACKGROUND: Coronary artery disease (CAD) is the leading cause of death in adults worldwide and its most important treatable risk factors are diabetes mellitus (DM), dyslipidemia and systemic hypertension (SH). The treatment with anti-hypertensives may cause undesirable changes in lipid profile, which diminishes its beneficial anti-atherogenic effects on the reduction of blood pressure. OBJECTIVE: To evaluate the lipid profile of type 2 diabetic subjects with essential hypertension treated only with captopryl or in combination with other anti-hypertensive drugs in order to show improvement in the lipid pattern of these patients, which leads to a protective effect. MATERIAL AND METHODS: We assessed total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C) and triglycerides (TG) levels of 140 patients, average age 59.7 ± 10.9, of both sexes, with type 2 diabetes and hypertension, referred to UNOESTE Laboratory of Clinical analysis. The glycemic control was determined by glycated hemoglobin (HG) levels. According to metabolic glycemic control (satisfactory or unsatisfactory), these patients were divided into two groups: treated only with captopril (DC); treated with a combination of hydrochlorothiazide (HCTZ) and DC. In patients with GH < 8.8 percent (controlled), DC and HCZT showed the following levels respectively: total cholesterol (210.2 ± 43.7 and 198.3 ± 37.5), HDL (49 ± 10.9 and 49.2 ± 8.7), LDL (126.9 ± 43.3 and 119.8 ± 23.8), TG (181.9 ± 86.4 and 161.2 ± 83.8) and G (151.3 ± 51.4 and 163 ± 66.5). There were no significant differences among them. In patients with GH > 11.2 percent (uncontrolled), DC and HCTZ showed the following levels respectively: total cholesterol (214.3 ± 45.9 and 197 ± 49.5), HDL (35.3 ± 20.5 and 41.5 ± 0.7), LDL (121 ± 43.3 and 116.5 ± 38.9), TG (271.5 ± 175.2 and 194 ± 49.5) and G (232.3 ± 102.9 and 272 ± 53.7). There were no significant differences, either. Nonetheless, it ...

Efecto de la inhibición de la síntesis de angiotensina II en el consumo de alcohol / Effect of angiotensin II synthesis inhibition on alcohol consumption

Background: Central reninangiotensin system modulates alcohol intake and inhibition of angiotensin converting enzyme reduces ethanol consumption in rats, and may be potentially useful in the treatment of alcoholism. Aim: To study the effect of captopríl on alcohol intake, both in humans and animals . Material and methods: In a double-blind, placebo-controlled clinical study, 15 alcoholics who met DSM-IV criíteria were randomized to receive captopril 100 mg/day or placebo for 12 weeks. In the experimental study, daily consumption of ethanol (10 percent v/v), water and solid food was assessed in 12 male Wistar rats before and after the intraperítoneal administration of captopríl 50 mg/kg/day. Results: In alcoholics, mean weekly standard alcoholic drínk consumption was not different during captopríl treatment or placebo. However, both groups had a signiñcantly lower intake than duríng baseline. Days of abstinence increased and days of drunkeness decreased in the group receiving captopril, when compared with baseline but not with placebo. Craving was significantly reduced by captopríl when compared with placebo. In rats, captopríl reduced not only alcohol consumption but also water and food intake. Conclusions: Captopríl decreases alcohol intake in rats and this effect is not speciñc for ethanol. Captopril did not alter alcohol consumption in alcoholics when compared with placebo but reduced craving.

Role of renin-angiotensin system in development of heart failure induced by myocardial infarction in rats

We investigated the morphologic and functional changes of infarcted rat hearts under a paradigm of angiotensinconverting enzyme inhibition. Myocardial infarction was induced by left coronary artery ligation and a control group (SHAM) underwent sham-operation. Infarcted rats received normal drinking water with (CAP group) or without (INF group) captopril. Functional assessment was performed by electro (ECG) and echocardiogram (ECHO) just before and 21 days after surgery. The ECG of INF and CAP showed similar values and resembled healed infarct after surgery. The most outstanding differences between INF and CAP were the prevention of the increase of P-wave and attenuation both in rightward deviation of the QRS axis and Q-wave amplitude in CAP compared with INF. The ECHO showed that captopril treatment improved the diastolic filling more than systolic performance. Cardiac dilatation and left congestive heart failure were observed only in INF. Both infarcted groups showed a scar tissue in the left ventricular wall, but the INF showed a higher scar area than CAP (49.7 ± 5.24 vs. 22.33 ± 6.19 respectively). These data suggest that the renin-angiotensin system induces morphologic and functional changes in post-infarcted rat hearts and which can be assessed by non-invasive exams.

Nós investigamos as alterações funcionais e morfológicas em corações de ratos infartados, sob o paradigma de inibição da enzima conversora de angiotensina. O infarto do miocárdio foi produzido pela ligadura da artéria coronária esquerda e um grupo falso-operado serviu de controle para o experimento. Os ratos infartados receberam água normal com (grupo CAP) ou sem (grupo INF) captopril. A avaliação funcional foi feita através de eletro (ECG) e ecocardiografia (ECO) momentos antes e 21 dias depois da cirurgia. O ECG dos grupos INF e CAP foram similares e compatíveis com infarto cicatrizado após a cirurgia. As principais diferenças entre os grupos INF e CAP foram: a prevenção do aumento da onda P e a atenuação tanto do desvio do eixo de despolarização ventricular como da amplitude da onda Q no CAP comparado com o INF. O ECO revelou que o tratamento com captopril foi mais efetivo em melhorar o enchimento diastólico do que aumentar a função sistólica. A dilatação e a falência cardíaca congestiva foram observadas apenas no INF. Ambos os grupos infartados exibiram um tecido cicatricial no ventrículo esquerdo, mas no INF esta se mostrou maior do que no CAP (49.7 ±5.24 vs. 22.33 ±6.19 respectivamente). Estes dados sugerem que o sistema renina angiotensina produz alterações morfológicas e funcionais em corações de ratos infartados e que estas podem ser detectadas por exames não invasivos.

Curso de Atualização em emergências médicas: aula 2: Urgências e emregências hipertensivas / Medical emergencies actualization course: class 2: hypertensive urgencies and emergencies

A hipertensão arterial é uma condição clínica com alta prevalência em todo o mundo, sendo fundamental estar atento às suas possíveis complicações. As emergências hipertensivas são condições associadas a risco iminente de vida, associadas à perda rápida da função de órgãos-alvo. Nesses casos a redução da pressão arterial deve ser imediata, em horas ou minutos. Nas urgências hipertensivas esse risco também existe, mas a redução da pressão arterial pode ser mais gradual, em cerca de 24 horas.

Captopril in the treatment of cardiovascular manifestations of indian red scorpion (Mesobuthus tamulus concanesis Pocock) envenomation.

OBJECTIVES: To study outcome of patients with scorpion envenomation treated with oral captopril in the ICU of a Tertiary Care, University Hospital in Mumbai. METHODS: Retrospective analysis of all patients with scorpion sting admitted to Medical Intensive Care Unit of a tertiary care university hospital in Mumbai between 1993 and 2003. RESULTS: Of 38 patients with cardiovascular manifestations, six had tachycardia alone and 8 had hypertension; these patients received oral captopril 12.5-25 mg thrice daily with no deaths. Pulmonary oedema with normal blood pressure and high central venous pressure (CVP) was seen in 10 patients. Five patients had hypotension, low CVP but no pulmonary oedema; with fluid infusion, these patients had correction of low CVP and hypotension, but developed pulmonary oedema. Pulmonary oedema resolved in all 15 patients with captopril (6.25-25 mg thrice daily): one patient died of ventricular tachycardia. Nine patients had cardiogenic shock; 6 patients, whose blood pressure improved with dopamine received, captopril; 1 of these 6 died. The other three patients did not respond to maximum vasopressor therapy and could not be given captopril; all three died. Four of the 5 deaths occurred in patients weighing < 25 kg suggesting that severity of cardiovascvlar manifestations also depends on body weight of the victim. CONCLUSION : Afterload reduction with oral captopril is safe and effective in scorpion envenomation with cardiovascular manifestations. Results are similar to those with other vasodilators.

Hipertensão arterial sistêmica no setor de emergência: o uso de medicamentos sintomáticos como alternativa de tratamento / Systemic hypertension at emergency units: the use of symptomatic drugs as choice for management

OBJETIVO: Comparar a resposta terapêutica dos pacientes atendidos no Setor de Emergência com sintomas e pressão arterial (PA) elevada, ao tratamento com medicacão sintomática ou anti-hipertensiva. MÉTODOS: Ensaio clínico randomizado, cego, envolvendo 100 pacientes atendidos na Emergência Cardiológica do Hospital Universitário Oswaldo Cruz com sintomas associados à pressão arterial sistólica (PAS) entre 180 e 200 mmHg e/ou pressão arterial diastólica (PAD) entre 110 e 120 mmHg. Os pacientes foram randomizados para tratamento com medicacão sintomática (dipirona ou diazepam) ou anti-hipertensiva (captopril). Aqueles portadores de qualquer condicão clínica associada, que necessitassem de tratamento imediato na Unidade de Emergência, foram excluídos do estudo. Atingiram o critério de alta os pacientes que, ao final do período de observacão de noventa minutos, tornaram-se assintomáticos e tiveram seus níveis tensionais sistólicos reduzidos para abaixo de 180 mmHg e diastólicos para aquém de 110 mmHg. RESULTADOS: A idade média da populacão estudada foi 54,4 anos. A maioria dos pacientes era do sexo feminino, hipertensos crônicos em tratamento farmacológico irregular, com baixa taxa de aderência às medidas não farmacológicas e classificados quanto ao índice de massa corpórea (IMC), em sobrepeso e obesos grau I. Cefaléia, dor torácica tipo D (não anginosa) e dispnéia foram as queixas mais freqüentes. A proporcão de pacientes tratados com medicacão sintomática que atingiu o critério de alta foi semelhante àquela de pacientes medicados com anti-hipertensivo (p=0,165). Não foi encontrada associacão entre o diagnóstico prévio de hipertensão arterial sistêmica (HAS) (p=0,192), tratamento farmacológico (p=0,687) e não-farmacológico e o critério de alta. CONCLUSAO: Uma maior proporcão (não significativa) de pacientes tratados com medicacão sintomática obtiveram reducão da PA aquém dos níveis estabelecidos no critério de alta e tornaram-se assintomáticos após o período de observacão.

Efeito do captrol no metabolismo de quilomícrons / Effect of captopril upon the chylomicrons metabolism

Avaliamos em 10 pacientes (8 mulheres) com hipertensão arterial leve ou moderada, 60,7  2,2 anos, o efeito do captopril: 1)na cinética plasmática dos quilomícrons (Qm) e seus remanescentes; 2)nas concentrações das lipoproteínas plasmáticas. Os resultados foram comparados a 20 indivíduos (15 mulheres) normotensos e normolipidêmicos, 60,5  1,5 anos (grupo controle). Concluímos que a remoção plasmática dos remanescentes de Qm, avaliada pelo teste da emulsão lipídica artificial, não se alterou com o uso de captopril. O emprego deste fármaco resultou em melhora significativa nas cocentrações plasmáticas de colesterol total e de LDL-c / The objective of this study was to verify in patients under captopril treatment: 1) the status of chylomicrons metabolism, using the chylomicron-like emulsion approach; 2) to evaluate plasma lipoprotein concentrations. The emulsion was injected intravenously into 10 mild or moderated hipertensive patients (8 women), 60.7 + 2.2 years. The results were compared to 20 normotensive and normolipidemic subjects (15 women), 60.5 + 1.5 years. Our study shows that captopril treatment does not disturb the removal from the plasma of chylomicron remnants and the plasma lipid and apolipoprotein profile. Captopril treatment may even bear an antiatherogenic effect, by decreasing LDL cholesterol...

A practical approach for the diagnosis and management of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) refers to a group of conditions of diverse etiology in which both ventricles are enlarged with reduced contractility. Certain correctable conditions associated with ventricular dysfunction can masquerade as DCM. Most of them can be identified with relatively inexpensive and readily available tests. A typical diagnostic work-up for a child with DCM also includes a number of investigations to identify the underlying cause, some of which are expensive and sophisticated. The average center in the developing world often does not have the facilities to carry out these investigations. The results of many of these investigations typically do not translate into a specific management strategy that makes a difference to prognosis. A significant number of children with DCM will eventually develop end-stage heart failure that requires cardiac transplantation with or without bridging procedures. This is an unrealistic option for the developing world. The management strategy of childhood DCM in the developing world needs to be tailored to the resources available with in a manner such that the overall prognosis is not substantially affected.

Study on early intervention with ACE inhibitor in myocardical infarction and short term outcome.

The present study was carried out on 100 patients with acute myocardial infarction (AMI) being treated with angiotensin converting enzyme (ACE) inhibitor and another 80 patients with conventional treatment but without ACE inhibitor during the period from May 1, 1995 to August 7, 1996 in Medical College, Calcutta. Clinical and other laboratory investigations including echocardiographic parameters were noted and recorded meticulously within 24-48 hours after AMI and repeated at 4th week. The present study based on non-invasive methods other than haemodynamic methods has shown that the echocardiographic assessment of left ventricular functional parameters after 4 weeks of ACE inhibitor therapy (n = 100) were better in treated group in comparison to control group without ACE inhibitor (n = 80) and the difference was statistically significant at 99% level of confidence. Overall mortality was 4% in ACE inhibitor group and 8.75% in the control group. This short term study with early intervention with ACE inhibitor within 48 hours of AMI has shown statistically significant evidence of beneficial effect of ACE inhibitor in improving the ventricular functional parameters and also reducing short term mortality from cardiac cause within 4 weeks compared to the group not receiving ACE inhibitors.

Effect of chronic oral administration of a low dose of captopril on sodium appetite of hypothyroid rats: Influence of aldosterone treatment

Rats rendered hypothyroid by treatment with methimazole develop an exaggerated sodium appetite. We investigated here the capacity of hypothyroid rats (N = 12 for each group) to respond to a low dose of captopril added to the ration, a paradigm which induces an increase in angiotensin II synthesis in cerebral areas that regulate sodium appetite by increasing the availability of circulating angiotensin I. In addition, we determined the influence of aldosterone in hypothyroid rats during the expression of spontaneous sodium appetite and after captopril treatment. Captopril significantly increased (P<0.05) the daily intake of 1.8 percent NaCl (in ml/100 g body weight) in hypothyroid rats after 36 days of methimazole administration (day 36: 9.2 + or - 0.7 vs day 32: 2.8 + or - 0.6 ml, on the 4th day after captopril treatment). After the discontinuation of captopril treatment, daily 1.8 percent NaCl intake reached values ranging from 10.0 + or - 0.9 to 13.9 ± 1.0 ml, 48 to 60 days after treatment with methimazole. Aldosterone treatment significantly reduced (P<0.05) saline intake before (7.3 + or - 1.6 vs day 0, 14.4 + or - 1.3 ml) and after captopril treatment. Our results demonstrate that, although hypothyroid rats develop a deficiency in the production of all components of the renin-angiotensin-aldosterone system, their capacity to synthesize angiotensin II at the cerebral level is preserved. The partial reversal of daily 1.8 percent NaCl intake during aldosterone treatment suggests that sodium retention reduces both spontaneous and captopril-induced salt appetite