Swim training reverses some effects of nandrolone decanoate in wistar rats / El entrenamiento en natación revierte algunos efectos del decanoato de nandrolona en los ratones wistar / Treinamento de natação reverte alguns efeitos do decanoato de nandrolona em ratos wistar

ABSTRACT Introduction: The indiscriminate use of androgenic steroids may have deleterious effects on human tissue. Objectives: Evaluate the effects of chronic administration of the steroid nandrolone decanoate (DECA) on autonomic cardiovascular modulation, kidney morphometry and the association between these variables in Wistar rats subjected to physical training with swimming. Methods: Thirty-two male Wistar rats aged 20 weeks were distributed among four experimental groups according to the training received: sedentary control (SC), sedentary treated with DECA (SD), trained control (TC) and trained treated with DECA (TD). The hemodynamic parameters, including blood pressure and variations in systolic blood pressure (SBPV) and diastolic blood pressure (DBPV), and kidney morphometry were evaluated. The level of significance adopted was 5%. Results: The SD group had higher baseline SBP and DBP values when compared to the SC, TC and TD groups, which were similar to each other. The rats in the SD group had higher systolic blood pressure (SBPV) and diastolic blood pressure (DBPV) variation values and higher absolute and normalized values in the LF band of the DBPV when compared to the animals in the SC, TC and TD groups. The animals in the SD group had a significantly higher rate of kidney fibrosis compared to the SC, TC and TD groups. There were no significant differences between the sympathetic modulation of SBPV through the LF component and kidney fibrosis. Conclusions: Physical training with swimming was effective in preventing the increase in blood pressure levels and lowering the occurrence of kidney fibrosis in animals treated with anabolic steroids. Level of Evidence IV; Series of cases .

RESUMEN Introducción: El uso indiscriminado de esteroides androgénicos puede tener consecuencias nocivas para el organismo. Objetivo: Evaluar los efectos de la administración crónica del esteroide decanoato de nandrolona (DECA) en ratones Wistar sometidos a entrenamiento físico con natación, sobre la modulación autonómica cardiovascular, morfometría renal y asociación entre esas variables. Métodos: Fueron utilizados 32 ratones Wistar machos con edad de 20 semanas, distribuidos en 4 grupos experimentales de acuerdo con el tratamiento recibido: sedentarios controles (SC), sedentarios que recibieron el DECA (SD), entrenados controles (EC) y entrenados que recibieron el DECA (ED). Se evaluaron parámetros hemodinámicos, como presión arterial y variación de la presión arterial sistólica (VPAS) y diastólica (VPAD) y morfometría renal. El nivel de significancia adoptado fue de 5%. Resultados: El grupo SD presentó valores basales mayores de PAS y PAD cuando comparados a los grupos SC, EC y ED, los cuales fueron semejantes entre sí. Los animales del grupo SD tuvieron valores mayores de la variancia de VPAS y VPAD y valores absolutos mayores y normalizados de la banda LF de la VPAD, en comparación con los animales de los grupos SC, EC y ED. El grupo SD tuvo tasa significativamente mayor de fibrosis renal en comparación con los animales de los grupos SC, EC y ED. No se evidenciaron diferencias considerables entre la modulación simpática de la VPAS a través del componente LF y fibrosis renal. Conclusiones: El entrenamiento físico con natación fue efectivo en prevenir el aumento de niveles presóricos y disminuir la ocurrencia de fibrosis renal en animales tratados con esteroide anabolizante. Nivel de Evidencia IV; Serie de casos .

RESUMO Introdução: O uso indiscriminado de esteroides androgênicos pode ter consequências deletérias no organismo. Objetivo: Avaliar os efeitos da administração crônica do esteroide decanoato de nandrolona (DECA) em ratos Wistar submetidos a treinamento físico com natação sobre a modulação autônoma cardiovascular, morfometria renal e associação entre essas variáveis. Métodos: Foram utilizados 32 ratos Wistar machos com idade de 20 semanas, distribuídos em 4 grupos experimentais de acordo com o tratamento recebido: sedentários controles (SC), sedentários que receberam o DECA (SD), treinados controles (TC) e treinados que receberam o DECA (TD). Avaliaram-se parâmetros hemodinâmicos, como pressão arterial e variação da pressão arterial sistólica (VPAS) e diastólica (VPAD) e morfometria renal. O nível de significância adotado foi de 5%. Resultados: O grupo SD apresentou valores basais maiores de PAS e PAD quando comparado aos grupos SC, TC e TD, os quais foram semelhantes entre si. Os animais do grupo SD tiveram valores maiores da variância da VPAS e VPAD e valores absolutos maiores e normalizados da banda LF da VPAD, em comparação com os animais dos grupos SC, TC e TD. O grupo SD teve taxa significativamente maior de fibrose renal em comparação com os animais dos grupos SC, TC e TD. Não se evidenciaram diferenças consideráveis entre a modulação simpática da VPAS através do componente LF e fibrose renal. Conclusões: O treinamento físico com natação foi efetivo em prevenir o aumento de níveis pressóricos e diminuir a ocorrência de fibrose renal em animais tratados com esteroide anabolizante. Nível de Evidência IV; Série de casos .

Effects of curcumin on cardiovascular risk factors in obese and overweight adolescent girls: a randomized clinical trial

ABSTRACT BACKGROUND: Obese adolescents are at higher risk of development of cardiovascular risk factors and obesity in later life. Dietary intake of antioxidants, particularly curcumin, as an active ingredient of turmeric extract, may have noticeable effects on obesity and its important complications such as cardiovascular risk factors. Therefore, the aim of this study was to assess the effects of curcumin supplementation on cardiovascular risk factors among overweight and obese female adolescents. DESIGN AND SETTING: Randomized placebo-controlled clinical trial; Pediatric Cardiovascular Research Center, Isfahan, Iran. METHODS: 60 adolescent girls (aged 13-18 years) were randomly assigned to receive either placebo or intervention. The adolescents were asked to consume one 500 mg tablet per day, containing either standardized 95% turmeric extract or placebo, and to undergo a weight maintenance or a mild weight loss diet for 10 weeks. Anthropometric and biochemical indices were assessed at the baseline and the end of the intervention. RESULTS: Curcumin supplementation had beneficial effects on body mass index (P = 0.019), waist circumference (P = 0.008), hip circumference (P = 0.030), high-density lipoprotein levels (P = 0.042) and triglyceride/high-density lipoprotein ratio (P = 0.021). However, in univariate analysis of covariance, no significant differences were found between the intervention and placebo groups after 10 weeks of supplementation (P > 0.05). CONCLUSIONS: Prescription of curcumin supplementation along with use of a slight weight loss diet might have beneficial effects on some cardiovascular risk factors among overweight and obese female adolescents. Larger clinical trials with higher curcumin doses and longer duration are needed to confirm the results from the current study. CLINICAL TRIAL REGISTRATION: IRCT20171107037302N1

Pharmacological effects of different chemotypes of Lippia alba (Mill.) N.E. Brown / Efectos farmacológicos de diferentes quimiotipos de Lippia alba (Mill.) N.E. Brown

The Lippia alba species consists of an aromatic plant used in Brazilian traditional medical practice and in the medical practice of several countries as well. Presenting a wide variability in its essential oil chemical composition, the Lippia alba is classified in chemotypes, or chemical races, according to the major constituents contained in its essential oil. Considering the quali and quantitative distribution of the components in the essential oil affect directly its pharmacological properties, which are presented in the medicinal species, this paper proposes a scientific literature review to correlate both biological and pharmacological properties presented by L. alba according to its chemical constitution.

Lippia alba es una planta aromática utilizada en la medicina tradicional de Brasil y de varios países. Con una gran variabilidad en la composición química de su aceite esencial, se clasifica en quimiotipos, o razas químicas, de acuerdo con los constituyentes mayoritarios presentes en el aceite esencial. Dado que la distribución cualitativa y cuantitativa de los componentes del aceite esencial afecta directamente a las propiedades farmacológicas presentadas por la especie medicinal, este trabajo propone realizar una revisión en la literatura científica para correlacionar las propiedades biológicas y farmacológicas de los quimiotipos presentes en el aceite essencial de la L. alba.

Comparative safety assessments of the biosimilar APZ001 and Erbitux in pre-clinical animal models

Abstract Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats / Modulação Serotoninérgica de Respostas Cardiovasculares Basais e Induzidas pela Expansão Isotônica do Volume Extracelular em Ratos

Abstract Background: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats.

Resumo Fundamento: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Objetivo: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. Métodos: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. Resultados: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). Discussão: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. Conclusão: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Effects of air pollution caused by sugarcane burning in Western São Paulo on the cardiovascular system

ABSTRACT OBJECTIVE To evaluate the effects of acute exposure to air pollutants (NO2 and PM10) on hospitalization of adults and older people with cardiovascular diseases in Western São Paulo. METHODS Daily cardiovascular-related hospitalization data (CID10 – I00 to I99) were acquired by the Department of Informatics of the Brazilian Unified Health System (DATASUS) from January 2009 to December 2012. Daily levels of NO2 and PM10 and weather data were obtained from Companhia Ambiental do Estado de São Paulo (CETESB – São Paulo State Environmental Agency). To estimate the effects of air pollutants exposure on hospital admissions, generalized linear Poisson regression models were used. RESULTS During the study period, 6,363 hospitalizations were analysed. On the day of NO2 exposure, an increase of 1.12% (95%CI 0.05–2.20) was observed in the interquartile range along with an increase in hospital admissions. For PM10, a pattern of similar effect was observed; however, results were not statistically significant. CONCLUSIONS Even though with values within established limits, NO2 is an important short-term risk factor for cardiovascular morbidity.

El consumo crónico de clorhidrato y/o pasta base de cocaína asocia envejecimiento arterial prematuro y aumento del riesgo cardiovascular / Chronic consumption of hydrochloride and / or cocaine base paste associates premature arterial aging and increased cardiovascular risk

Introducción: el consumo de cocaína en forma de clorhidrato (CC), y especialmente de su pasta base (PBC), es un problema sanitario mayor, entre otros factores, por su incidencia, repercusión y franja etaria a la que involucra. Múltiples efectos cardiovasculares han sido descritos en asociación con el consumo de CC, pero el impacto a corto/mediano plazo del uso crónico de CC y PBC en el sistema arterial en sujetos jóvenes no se ha estudiado. Objetivo: determinar la prevalencia de cambios (alteraciones) arteriales estructurales y/o funcionales en jóvenes consumidores de cocaína o sus derivados. Material y método: se incluyeron 29 sujetos (27 hombres; edad media/rango: 29/20-35 años) con criterios toxicológicos de dependencia a cocaína, más de dos años de consumo, y abstinencia menor a un mes. Se realizó evaluación clínica y paraclínica para cuantificar el riesgo cardiovascular global (escore de riesgo de Framingham [EF] para enfermedad cardiovascular a diez años). Los estudios incluyeron determinación de: 1) presencia de placas de ateroma carotídeas y espesor íntima-media carotídeo (EIMC; ecografía modo-B color y software específico). 2) Rigidez aórtica regional (mediante velocidad de la onda del pulso, [VOP]). 3) Presión de pulso aórtica central (tonometría de aplanamiento). 4) Índice tobillo-brazo (oscilometría). 5) Reactividad vascular, función endotelial, por vasodilatación mediada por flujo (DMF; ecografía modo-B y software específico). Se determinó la edad vascular (EV) mediante análisis multiparamétrico. El envejecimiento arterial precoz (EAP) se definió como la diferencia entre la EV y la edad cronológica. Los datos obtenidos se compararon con valores de normalidad (sujetos control). Resultados: de los 29 pacientes, 10 fueron consumidores de CC, 3 de PBC y 16 de ambas sustancias. El 90% eran fumadores de cigarrillos (promedio de consumo: 14,4 cigarrillos/día). Si bien ningún paciente presentó VOP >10 m/s (punto de normalidad aceptado por la Sociedad Europea de Cardiología), 63,6% tuvo niveles de VOP entre el percentil (p)50 y el p90 de la población control de referencia, y 13,6% por encima del p90 de la misma población, indicando que el 77,2% de los mismos presentaron VOP >p50. Respecto del EIMC, un 8% de los pacientes estudiados tuvo niveles > 0,9 mm, y 69% niveles por encima del p95 de la población de referencia, para sexo y edad.. El análisis de la función endotelial mostró que 13,6% de los pacientes no presentó dilatación arterial (DMF £ 0%) y 36% presentó DMF £ 5%. Finalmente, el 33% de los pacientes presentó niveles de presión de pulso aórtica por encima del nivel umbral (p95), para sexo y edad. La EA fue de 37,1 ± 8,4 años, indicando la existencia de un EAP de 8,1 ± 6,2 años (rango: 3-24 años). Conclusión: los usuarios de cocaína mostraron cambios subclínicos perjudiciales a nivel arterial que se asocian a mayor riesgo cardiovascular. Sus parámetros arteriales presentaron niveles compatibles con los existentes en una población control con una edad de 8,1 ± 6,2 años mayor que la estudiada, indicando que los consumidores de CC y PBC podrían presentar "envejecimiento arterial precoz".

Introduction: cocaine consumption, in particular cocaine base paste, is a major health problem, among other factors, its incidence, impact, and the age group involved. Multiple cardiovascular effects have been described in association with cocaine use but the impact in the short/medium-term chronic use of hydrochloride cocaine and cocaine base paste in the arterial system in young subjects has not been studied.Objective: to determine the prevalence of changes (alterations) arterial structural and/or functional in young cocaine or its derivatives users Method: 29 subjects (age: 20-35 years; 27 men) with toxicological criteria for cocaine dependence, over 2 years old and less than one month withdrawal were included. Clinical and paraclinical evaluation was conducted to quantify the global cardio-vascular risk (10-years Framingham Risk Score for cardiovascular disease). The studies included determination of: 1) presence of carotid atheromatous plaques and carotid intima-media thickness (CIMT; color and B-mode ultra sound and specific software), 2) assessment of regional aortic stiffness by pulse wave velocity (PWV), 3) evaluation of central aortic pulse pressure by applanation tonometry, 4) ankle-brachial index, by oscillometry and 5) vascular reactivity (endothelial function) by flow mediated dilatation (FMD) with B-mode ultra sound and specific software. The vascular age (VA) was calculated by multiparametric analysis. The arterial aging (AA) was defined as the difference between the VA and chronological age. The obtained data were compared with normal values (control subjects). Results: 29 patients were evaluated, 10 patients were users of hydrochloride cocaine, 3 cocaine base paste and 16 of both substances. 90% of patients were smokers (mean consumption: 14.4 cigarettes/day). Although no patient had PWV values above 10 m/s, 63,6% had levels of PWV between p50 and p90 and 13,6% above the p90, indicating that 77% of them presented by PWV over p50. Regarding the CIMT, 8% of the patients studied had levels above 0,9 mm, and 69% higher than p75 levels to age and sex. The endothelial function analysis showed that 13,6% of patients had no arterial dilation (FMD £ 0%) and 36% presented a £ 5% FMD. Finally, 33% of patients had levels of aortic pulse pressure above the threshold level (p95 of the reference control group) for gender and age. The AA was 37.1±8.4 years, indicating the existence of early arterial aging 8.1±6.2 years (range 3-24 years). Conclusion: cocaine users showed adverse subclinical level changes of the structure and function of the arteries which is associated with increased cardiovascular risk. The levels obtained for different arterial parameters evaluated were consistent with those in a control population with an age 8.1±6.2 years older than the study, indicating that users of hydrochloride cocaine and cocaine base paste might present "early arterial aging."

Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats / Alterações cardiovasculares da exposição perinatal ao chumbo em ratos jovens e adultos: papel da terapia combinada

Background: Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. Objective: To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Results: Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). Conclusions: All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These ...

Introdução: A terapia combinada parece desempenhar papel significativo em reduzir os efeitos cardiovasculares deletérios da exposição ao chumbo (Pb). Objetivo: Para investigar esta possibilidade, ratas Wistar receberam Pb (500 ppm na água de beber) ou água durante a prenhez e a lactação. Ratos com 22 e 70 dias, expostos perinatalmente ao Pb ou não, receberam DMSA, L- arginina, enalapril e a combinação destes por 30 dias adicionais. Métodos: Curvas concentração-efeito à noradrenalina foram obtidas em aortas intactas e desnudas, de ratos com 23, 52, 70 e 100 dias expostos ou não ao Pb, tratados ou não. Resultados: A pressão arterial sistólica caudal (mmHg) foi avaliada e mostrou-se aumentada em ratos expostos ao Pb [23, 52, 70 e 100 dias, respectivamente: controle 107,1±1,8, 118,8±2,1, 126,1±1,1, 120,5±2,2; Pb 117,8±3,9*, 135,2±1,3*, 139,6±1,6* e 131,7± 2,8*]. Observou-se aumento de reatividade à noradrenalina em aorta intacta, mas não desnudada, de ratos com 52, 70 e 100 dias expostos ao Pb [resposta máxima (g de tensão) 52 dias: Pb 3,43±0,16*, controle 2,38±0,33; 70 dias: Pb 4,32±0,18*, controle 3,37±0,13; 100 dias: Pb 4,21±0,23*, controle 3,22±0,21]. (*) p < 0,05 em relação ao respectivo controle. Conclusões: Todos os tratamentos restauraram as alterações de reatividade à noradrenalina em aortas de ratos expostos perinatalmente ao Pb. Exceto pelo enalapril em ratos jovens, a terapia combinada restaurou mais precocemente a pressão arterial de ratos expostos ao Pb em relação aos tratamentos isolados. Estes resultados representam uma nova abordagem no desenvolvimento de protocolos terapêuticos no tratamento da hipertensão induzida pela exposição ao Pb. .

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05) to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05). CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats. .

Toxic effects of mercury, lead and gadolinium on vascular reactivity

Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.

Contracepção hormonal e sistema cardiovascular / Hormonal contraception and cardiovascular system / Contracepción hormonal y sistema cardiovascular

A contracepção hormonal é o método mais utilizado para prevenção de gestações não planejadas. A literatura tem demonstrado associação entre risco cardiovascular e uso de hormonioterapia. A fim de melhorar a orientação contraceptiva para mulheres com fatores de risco para doença cardiovascular, realizamos uma revisão da literatura em relação ao assunto. Esta revisão descreve os dados mais recentes da literatura científica acerca da influência dos contraceptivos hormonais em relação a trombose venosa, arterial e hipertensão arterial sistêmica, doenças cada dia mais prevalentes na população feminina jovem.

Hormonal contraception is the most widely used method to prevent unplanned pregnancies. The literature has shown an association between cardiovascular risk and use of hormone therapy. With the purpose of providing better guidelines on contraception methods for women with risk factors for cardiovascular disease, we have reviewed the literature on the subject. This review describes the latest data from the scientific literature concerning the influence of hormonal contraceptives on arterial thrombosis, venous thrombosis and systemic high blood pressure, which are diseases that have become increasingly prevalent among young females.

La contracepción hormonal es el método más utilizado para la prevención de los embarazos no planificados. La literatura ha venido demostrando la asociación que existe entre el riesgo cardiovascular y el uso de la hormonoterapia. Con el objetivo de mejorar la orientación en la contracepción en mujeres con factores de riesgo para el desarrollo de enfermedad cardiovascular, realizamos una revisión de la literatura con relación a ese asunto. Esa revisión describe los datos más recientes de la literatura científica acerca de la influencia de los anticonceptivos hormonales con relación a la trombosis venosa, arterial e hipertensión arterial sistémica, enfermedades cada día más prevalentes en la población femenina joven.

Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats

OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n=8), fructose (n=8), and fructose+ simvastatin (n=8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4+ 0.32 percent/min) relative to that in the control group (4.4+ 0.29 percent/min). Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4+0.66 percent/min). The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124+2 mmHg and fructose+simvastatin: 126 + 3 mmHg vs. controls: 112 + 2 mmHg). The sympathetic effect was enhanced in the fructose group (73 + 7 bpm) compared with that in the control (48 + 7 bpm) and fructose+simvastatin groups (31+8 bpm). The vagal effect was increased in fructose+simvastatin animals (84 + 7 bpm) compared with that in control (49 + 9 bpm) and fructose animals (46+5 bpm). CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the hypothesis that statins reduce the cardiometabolic risk in females with metabolic syndrome.

Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs [NSAIDs] confer a gastrointestinal [GI] side effect profile and concerns regarding adverse cardiovascular effects have emerged associated with considerable morbidity and mortality. NSAIDs are highly effective in treating pain and inflammation, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although they may increase cardiovascular adverse events. The selection of an appropriate analgesic or antiinflammatory agent with or without gastroprotective therapy should be individualized

Comparison of the effect of fentanyl, sufentanil, alfentanil and remifentanil on cardiovascular response to tracheal intubation in children

Laryngoscopy and tracheal intubation may cause significant cerebral and systemic hemodynamic responses. Many drugs have been shown to be effective in modifying these hemodynamic responses, including fentanyl, sufentanil, alfentanil and remifentanil. The purpose of the current study was to compare the efficacy of fentanyl, sufentanil, alfentanil and remifentanil on blunting cardiovascular changes during laryngoscopy and intubation in children. Eighty children, 1-6 years old, classified as American Society of Anesthesiologists physical status I and II who were scheduled for elective surgery with general anesthesia and orotracheal intubation, were enrolled in this randomized and double-blinded study. Patients were randomly assigned into four groups of 20 patients. Group F received fentanyl 1 micro g/kg[-1], group S received sufentanil 0.1 micro g/kg[-1], group A received alfentanil 10 micro g/kg[-1] and group Rreceived remifentanil 1 micro g/kg[-1] intravenously. After establishment of neuromuscular blockade confirmed with a nerve stimulator, laryngoscopy and orotracheal intubation were performed 3 min after induction. Hemodynamic variables including systolic and diastolic blood pressure [SAP, DAP] and heart rate [HR] were recorded at base line [before opioid administration], before laryngoscopy and one minute after orotracheal intubation. The patients' characteristics and laryngoscopy grade were similar in all groups. There was no significant difference in the mean values of SAP, DAP and HR at each measured time between the four groups. There was significant difference in the mean values of SAP, DAP and HR measured over time in each group. The intravenous fentanyl attenuated laryngoscopy-induced SAP, DAP and HR increases better than sufentanil, alfentanil or remifentanil and hemodynamic stability is better preserved with fentanyl

Evaluation of two regional anesthetic methods on the front limb of dogs using hyperbaric bupivacaine / Avaliação de dois métodos de bloqueios anestésicos regionais no membro anterior em cães usando bupivacaína hiperbárica

PURPOSE: To evaluate the effects of bupivacaine 0.5 and 0.25 percent in intravenous regional anesthesia (IVRA) and brachial plexus block (BPB), respectively, on anesthesia, motor block and cardiovascular parameters in dogs. METHODS: Fourteen healthy adult dogs averaging 10 kilograms (kg) of body weight. Animals were randomly assigned to receive one of the two treatments IVRA (n=7) or BPB (n=7). All the animals were sedated with acepromazine (0.1 mg/kg intramuscular). To execute the BPB was used an electrical nerve stimulation. Anesthesia, motor block, sedation, cardiovascular and respiratory effects were measured as effect of the treatment. RESULTS: BPA showed superior efficiency and duration of anesthesia (BPB - 456 ± 94 minutes vs IVRA - 138 ± 44) as well as motor block. There only physiologic parameter which change were the systolic pressure in BPB and respiratory rate for both treatments. CONCLUSION: In dogs the 0.25 percent hyperbaric bupivacaine in BPB produces a front limb anesthesia about three times more than the 0.5 percent in IVRA, with ptosis of the limb blocked and little interference in the cardiovascular system but with decrease in respiratory rate.

OBJETIVO: Avaliar os efeitos da bupivacaína 0,5 e 0,25 por cento na anestesia regional endovenosa (IVRA) e no bloqueio do plexo braquial (BPB) respectivamente, na anestesia, bloqueio motor e parâmetros cardiovasculares em cães. MÉTODOS: Foram utilizados 14 cães sadios adultos pesando em média 10 kilos. Animais foram aleatoriamente designados a um de dois tratamentos IVRA (n = 7) ou BPB (n = 7). Todos os animais foram sedados com acepromazina (0,1 mg/kg intramuscular). Para realizar o BPB foi usado um estimulador elétrico nervoso. Anestesia, bloqueio motor, sedação, efeitos cardiovascular e respiratório foram mensurados como efeitos dos respectivos bloqueios. RESULTADOS: O bloqueio BPB demonstrou eficiência superior e maior duração da anestesia (BPB - 456 ± 94 minutos vs IVRA - 138 ± 44 minutos) bem como maior envolvimento motor. Somente a pressão arterial sistólica foi alterada no grupo BPB e a freqüência respiratória em ambos os tratamentos. CONCLUSÃO: Em cães, a bupivacaína 0,25 por cento hiperbárica no grupo BPB produziu uma anestesia do membro anterior três vezes mais longa que a 0,5 por cento no grupo IVRA, com ptose do membro bloqueado e pequena interferência no sistema cardiovascular e com diminuição da freqüência respiratória.

Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais / Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects

Os anti-inflamatórios não esteroides (AINEs) encontram-se entre os medicamentos mais prescritos em todo o mundo. Essa classe heterogênea de fármacos inclui a aspirina e vários outros agentes inibidores da ciclo-oxigenase (COX), seletivos ou não. Os AINEs não seletivos são os mais antigos, e designados como tradicionais ou convencionais. Os AINEs seletivos para a COX-2 são designados COXIBEs. Nos últimos anos, tem sido questionada a segurança do uso dos AINEs na prática clínica, particularmente dos inibidores seletivos da COX-2. As evidências sobre o aumento do risco cardiovascular com o uso de AINEs são ainda incompletos, pela ausência de ensaios randomizados e controlados com poder para avaliar desfechos cardiovasculares relevantes. Entretanto, os resultados de estudos clínicos prospectivos e de meta-análises indicam que os inibidores seletivos da COX-2 exercem importantes efeitos cardiovasculares adversos, que incluem aumento do risco de infarto do miocárdio, acidente vascular cerebral, insuficiência cardíaca, insuficiência renal e hipertensão arterial. O risco desses efeitos adversos é maior em pacientes com história prévia de doença cardiovascular ou com alto risco para desenvolvê-la. Nesses pacientes, o uso de inibidores da COX-2 deve ser limitado àqueles para os quais não há alternativa apropriada e, mesmo assim, somente em doses baixas e pelo menor tempo necessário. Embora os efeitos adversos mais frequentes tenham sido relacionados à inibição seletiva da COX-2, a ausência de seletividade para essa isoenzima não elimina completamente o risco de eventos cardiovasculares, de modo que todos os fármacos do largo espectro dos AINEs somente devem ser prescritos após consideração do balanço risco/benefício.

The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most often prescribed drugs in the world. This heterogeneous class of drugs includes aspirin and several other selective or non-selective cyclooxygenase (COX) inhibitors. The non-selective NSAIDs are the oldest ones and are called traditional or conventional NSAIDs. The selective NSAIDs are called COX-2 inhibitors. In recent years, the safety of NSAID use in clinical practice has been questioned, especially that of the selective COX-2 inhibitors. The evidence on the increase in cardiovascular risk with the use of NSAIDs is still scarce, due to the lack of randomized and controlled studies with the capacity of evaluating relevant cardiovascular outcomes. However, the results of prospective clinical trials and meta-analyses indicate that the selective COX-2 inhibitors present important adverse cardiovascular effects, which include increased risk of myocardial infarction, cerebrovascular accident, heart failure, kidney failure and arterial hypertension. The risk of these adverse effects is higher among patients with a previous history of cardiovascular disease or those at high risk to develop it. In these patients, the use of COX-2 inhibitors must be limited to those for which there is no appropriate alternative and, even in these cases, only at low doses and for as little time as possible. Although the most frequent adverse effects have been related to the selective COX-2 inhibition, the absence of selectiveness for this isoenzyme does not completely eliminate the risk of cardiovascular events; therefore, all drugs belonging to the large spectrum of NSAIDs should only be prescribed after consideration of the risk/benefit balance.

Repercussão cardiovascular, com e sem álcool, do carbonato de lodenafila, um novo inibidor da PDE5 / Repercusión cardiovascular, con y sin alcohol, del carbonato de lodenafila, un nuevo inhibidor de la PDE5 / Cardiovascular repercussion of lodenafil carbonate, a new PDE5 inhibitor, with and without alcohol consumption

FUNDAMENTO: A disfunção erétil afeta um grande número de homens no mundo e os inibidores de PDE 5 (iPDE5) estão entre os principais métodos de tratamento desses pacientes. O consumo social de álcool e o ato sexual apresentam uma relação considerável. Portanto, a associação entre álcool e iPDE5 pode ocorrer. O carbonato de lodenafila é um novo iPDE5 desenvolvido por uma empresa brasileira. OBJETIVO: Avaliar a repercussão cardiovascular do carbonato de lodenafila, associado ou não ao álcool, assim como as alterações na farmacocinética que esta associação possa determinar. MÉTODOS: Estudo realizado com 15 voluntários sadios que receberam em momentos diferentes o carbonato de lodenafila (CL) na dose de 160 mg em jejum, CL (160 mg) com álcool, ou somente placebo. Esses pacientes foram monitorados por 24 horas, sendo avaliado o quadro clínico, a pressão arterial (PA), a frequência cardíaca (FC), o intervalo QT e também os dados de farmacocinética. RESULTADOS: O carbonato de lodenafila, isoladamente ou associado com álcool, não determinou alterações clínicas significativas na PA ou FC, embora tenha ocorrido diminuição da PA estatisticamente significativa após 4 horas, nos voluntários que receberam medicamento e álcool, assim como um aumento da FC após 6 horas nos pacientes que receberam o CL. A análise do intervalo QT corrigido não mostrou alteração significativa. O álcool aumentou a biodisponibilidade do medicamento em 74 por cento. Houve somente 2 queixas de cefaleia leve, possivelmente associada ao medicamento. CONCLUSÃO: O carbonato de lodenafila, mesmo associado ao álcool, não determinou repercussões clínicas importantes na PA, FC, ou alterações no intervalo QTc; a ingestão com álcool, por sua vez, aumentou significativamente sua biodisponibilidade.

BACKGROUND: Millions of men around the world suffer from erectile dysfunction, for which phosphodiesterase 5 inhibitors (PDE-5 inhibitors) are currently the first treatment option. Sexual activity and alcohol consumption are closely related, and the simultaneous use of alcohol and PDE-5 inhibitors can happen. Lodenafil carbonate is a new PDE-5 inhibitor, developed by a Brazilian pharmaceutical company. OBJECTIVE: This work aimed at evaluating the cardiovascular safety of lodenafil carbonate, with and without simultaneous alcohol consumption. METHODS: Fifteen male volunteers received 160 mg lodenafil carbonate (LC), in three different moments. Participants were assigned to three groups, treated with LC in fasting condition, with alcohol or receiving only placebo. The volunteers were continuously monitored during 24 hours for physical impairment, blood pressure, heart rate, QT interval and lodenafil's pharmacokinetic parameters. RESULTS: Lodenafil carbonate alone or with alcohol did not induce clinically relevant modifications in arterial blood pressure or heart rate. A statistically significant decrease in blood pressure was seen four hours after LC and alcohol intake, and an increase in heart rate six hours after intake of lodenafil carbonate alone. The QTc interval was not significantly modified. Lodenafil carbonate bioavailability was increased in 74 percent when drug intake was associated with alcohol. CONCLUSION: These results show that the use of lodenafil carbonate did not have clinically relevant effects on blood pressure or heart rate, and was not associated with QT interval prolongation. The association of lodenafil carbonate and alcohol affected its pharmacokinetic properties, increasing the bioavailability of the drug.

FUNDAMENTO: La disfunción eréctil afecta a un gran número de hombres en el mundo y los inhibidores de PDE5 (iPDE5) están entre los principales métodos de tratamiento de estos pacientes. El consumo social de alcohol y el acto sexual presentan una relación considerable. Por lo tanto, puede ocurrir una asociación entre alcohol e iPDE5. El carbonato de lodenafila es un nuevo iPDE5 desarrollado por una empresa brasileña. OBJETIVO: Evaluar la repercusión cardiovascular del carbonato de lodenafila, asociado o no al alcohol, así como las alteraciones en la farmacocinética que esta asociación pueda determinar. MÉTODOS: Estudio realizado con 15 voluntarios sanos que recibieron en momentos diferentes el carbonato de lodenafila (CL) en la dosis de 160mg en ayunas, CL (160 mg) con alcohol, o solamente placebo. Estos pacientes fueron monitoreados por 24 horas, siendo evaluado el cuadro clínico, la presión arterial (PA), la frecuencia cardíaca (FC), el intervalo QT y también los datos de farmacocinética. RESULTADOS: El carbonato de lodenafila, aisladamente o asociado con alcohol, no determinó alteraciones clínicas significativas en la PA o FC, aunque se haya registrado una disminución de la PA estadísticamente significativa después de 4 horas en los voluntarios que recibieron medicamento y alcohol, así como un aumento de la FC después de 6 horas en los pacientes que recibieron el CL. El análisis del intervalo QT corregido no mostró alteración significativa. El alcohol aumentó la biodisponibilidad del medicamento en un 74 por ciento. Se registraron sólo 2 quejas de cefalea leve, posiblemente asociada al medicamento. CONCLUSIÓN: El carbonato de lodenafila, aun asociado al alcohol, no determinó repercusiones clínicas importantes en la PA, FC, o alteraciones en el intervalo QTc; la ingestión con alcohol, a su vez, aumentó significativamente su biodisponibilidad.