Impacto dos stents e do sirolimus por via oral na vasomotilidade coronariana dependente e independente do endotelio / Impact of stenting and oral sirolimus on endothelium-dependent and independent coronary vasomotion

FUNDAMENTO: Não há consenso sobre o impacto do implante de stent sobre a função endotelial no longo prazo. Há relatos de disfunção endotelial aumentada com stent com sirolimus quando comparado com o stent metálico convencional (BMS). OBJETIVO: Este estudo visa a avaliar o impacto do BMS e o efeito do sirolimus por via oral sobre a função endotelial. MÉTODOS: Quarenta e cinco pacientes foram randomizados em três grupos: BMS + altas doses de sirolimus oral (dose inicial de 15 mg, seguida de 6 mg/dia durante quatro semanas); BMS + baixa dose de sirolimus (6 mg, seguida de 2 mg por dia durante quatro semanas) e BMS sem sirolimus. Mudanças na vasoconstrição ou vasodilatação, em um segmento de 15 milímetros começando pelo extremo distal do stent em resposta a acetilcolina e nitroglicerina, foram avaliadas por angiografia quantitativa. RESULTADOS: Os grupos apresentaram características angiográficas semelhantes. A variação percentual de diâmetro em resposta a acetilcolina foi semelhante em todos os grupos, nos dois momentos (p = 0,469). Quatro horas após o implante de stent, o segmento alvo apresentou uma disfunção endotelial que se manteve após oito meses em todos os grupos. Em todos os grupos, a vasomotricidade independente de endotélio em resposta a nitroglicerina foi semelhante, às quatro horas e aos oito meses, com diâmetro do segmento alvo aumentado após a infusão de nitroglicerina (p = 0,001). CONCLUSÃO: A disfunção endotelial esteve igualmente presente no segmento distal de 15 milímetros do segmento tratado, às 4 horas e aos 8 meses após implante do stent. O sirolimus administrado por via oral durante quatro semanas para evitar a reestenose não afetou o estado de vasomotricidade endotélio dependente e independente.

BACKGROUND: There is no consensus regarding the impact of stenting on long-term endothelial function. There have been reports of increased endothelial dysfunction with sirolimus-eluting stents as compared to bare metal stenting (BMS). OBJECTIVE: This study aims to assess the impact of BMS and the effect of oral sirolimus on endothelial function. METHODS: Forty-five patients were randomized into three groups: BMS + high-dose oral sirolimus (initial dose of 15 mg, followed by 6 mg/day for four weeks); BMS + low-dose sirolimus (6 mg followed by 2 mg daily for four weeks); and BMS without sirolimus. Changes in vasoconstriction or vasodilation in a 15 mm segment starting at the distal stent end in response to acetylcholine and nitroglycerin were assessed by quantitative angiography. RESULTS: The groups had similar angiographic characteristics. The percent variation in diameter in response to acetylcholine was similar in all groups at the two time points (p = 0.469). Four hours after stenting, the target segment presented an endothelial dysfunction that was maintained after eight months in all groups. In all groups, endothelium-independent vasomotion in response to nitroglycerin was similar at four hours and eight months, with increased target segment diameter after nitroglycerin infusion (p = 0.001). CONCLUSION: The endothelial dysfunction was similarly present at the 15 mm segment distal to the treated segment, at 4 hours and 8 months after stenting. Sirolimus administered orally during 4 weeks to prevent restenosis did not affect the status of endothelium-dependent and independent vasomotion.

Efeito vasomotor após intoxicação aguda com bupivacaína e levobupivacaína via intraperitoneal em ratos, analisado por imagem infravermelha digital / Vasomotor effect after acute intoxication with bupivacaine and levobupivacaine in rats via intraperitoneal route analyzed via digital infrared imaging

JUSTIFICATIVA E OBJETIVOS: O estudo do efeito vasomotor dos anestésicos locais (AL) é de suma importância para a análise da ocorrência de efeitos cardiotóxicos, neurotóxicos e interações medicamentosas. Com a finalidade de encontrar um fármaco mais seguro do que a bupivacaína racêmica, o presente estudo teve por objetivo a análise por imagem infravermelha digital do efeito vasomotor da intoxicação aguda da bupivacaína e da levobupivacaína via intraperitoneal em ratos. MÉTODO: Utilizaram-se 30 ratos machos da linhagem Wistar, alocados em três grupos (n = 10) e submetidos a uma injeção intraperitoneal de AL. No Grupo C (Controle), foi realizada injeção intraperitoneal de soro fisiológico 0,9 por cento 1 mL. No Grupo B (bupivacaína), injeção intraperitoneal de bupivacaína racêmica a 0,5 por cento (R50-S50), dose de 20 mg.kg-1 de peso. No Grupo L (levobupivacaína), injeção intraperitoneal de levobupivacaína a 0,5 por cento, excesso enantiomérico (S75-R25) em dose de 20 mg.kg-1 de peso. Procedeu-se à filmagem termográfica contínua desde o momento da pré-injeção até 30 minutos após a injeção. Os resultados das filmagens foram analisados em forma gráfica, verificando-se a temperatura máxima de cada rato e a temperatura média do sistema que abrigava o animal. RESULTADOS: Os resultados da análise gráfica revelaram que não houve diferença entre o Grupo L e o Grupo C, e a temperatura média permaneceu estável durante todo o experimento em ambos os grupos. No Grupo B, houve um fenômeno de aumento de temperatura após a injeção intraperitoneal de bupivacaína. CONCLUSÕES: Os resultados demonstraram que o efeito vasomotor da toxicidade aguda da levobupivacaína foi semelhante ao Grupo C com soro fisiológico, por meio de estudos macroscópicos por filmagem digital infravermelha, e que houve alterações vasomotoras (vasoconstrição) com a intoxicação por bupivacaína em relação ao Grupo C e em relação ao Grupo L.

BACKGROUND AND OBJECTIVES: The study of the vasomotor effect of local anesthetics (LA) is of paramount importance for the analysis of the occurrence of cardiotoxic and neurotoxic effects, and drug interactions. In order to find a safer drug than racemic bupivacaine, this study aimed to analyze digital infrared imaging of acute vasomotor effect of bupivacaine and levobupivacaine in rats intraperitoneally. METHOD: We used 30 male Wistar rats distributed into three groups (n = 10) and subjected to an intraperitoneal injection of LA. In Group C (control) 1 mL 0.9 percent saline was injected intraperitoneally. In Group B (bupivacaine), intraperitoneal injection of 0.5 percent of racemic bupivacaine (S50-R50), dose of 20 mg.kg-1 of body weight. In Group L (levobupivacaine), intraperitoneal injection of levobupivacaine 0.5 percent enantiomeric excess (S75-R25) in dose of 20 mg.kg-1 of body weight. The procedure was thermographicly continuously filmed from the time of pre-injection until 30 minutes after injection. The results of the recordings were analyzed in graphical form, verifying the maximum temperature of each rat and the average temperature of the system that housed the animal. RESULTS: The results of graphic analysis showed no difference between Group L and Group C, and the average temperature remained stable through-out the experiment in both groups. In Group B, there was a phenomenon of temperature increase after intraperitoneal injection of bupivacaine. CONCLUSIONS: The results demonstrated that the vasomotor effect of the acute toxicity of levobupivacaine was similar to Group C with saline, through macroscopic studies by infrared digital filmmaking, and that there were vasomotor changes (vasoconstriction), with bupivacaine intoxication in relation to both Group C and Group L.

JUSTIFICATIVA Y OBJETIVOS: El estudio del efecto vasomotor de los anestésicos locales (AL), es de suma importancia para el análisis del aparecimiento de efectos cardiotóxicos, neurotóxicos e interacciones medicamentosas. Con el fin de encontrar un fármaco más seguro que la bupivacaína racémica, el presente estudio se propuso analizar por imagen infrarroja digital, el efecto vasomotor de la intoxicación aguda de la bupivacaína y de la levobupivacaína vía intraperitoneal en ratones. MÉTODO: Fueron usados 30 ratones machos de la raza Wistar, divididos en tres grupos (n = 10) y sometidos a una inyección intraperitoneal de AL. En el Grupo C (Control), fue realizada una inyección intraperitoneal de suero fisiológico al 0,9 por ciento 1 mL. En el Grupo B (bupivacaína), una inyección intraperitoneal de bupivacaína racémica al 0,5 por ciento (R50-S50), dosis de 20 mg.kg-1 de peso. En el Grupo L (levobupivacaína), una inyección intraperitoneal de levobupivacaína al 0,5 por ciento, con exceso enantiomérico (S75-R25) en dosis de 20 mg.kg-1 de peso. Después de procedió a la filmación termográfica continua desde el momento anterior a la inyección hasta 30 minutos después de ella. Los resultados de las filmaciones se analizaron de forma gráfica, verificando la temperatura máxima de cada ratón y la temperatura promedio del sistema que abrigaba al animal. RESULTADOS: Los resultados del análisis gráfico revelaron que no hubo diferencia entre el Grupo L y el Grupo C, y que la temperatu-ra promedio se mantuvo estable durante todo el experimento en los dos grupos. En el Grupo B, se produjo un fenómeno de aumento de temperatura después de la inyección intraperitoneal de bupivacaína. CONCLUSIONES: Los resultados demostraron que el efecto vasomotor de la toxicidad aguda de la levobupivacaína fue similar al Grupo C con suero fisiológico, por medio de estudios macroscópicos por filmación digital infrarroja, y que se produjeron alteraciones vasomotoras (vasoconstricción)...

Efficacy and safety of Pueraria mirifica (Kwao Kruea Khao) for the treatment of vasomotor symptoms in perimenopausal women: Phase II Study.

OBJECTIVES: To evaluate the preliminary efficacy and safety of Pueraria mirifica in the treatment of vasomotor symptoms. DESIGN: Open-label study. SETTING: Hat Yai Regional Hospital, Thailand. SUBJECTS: Pre and postmenopausal women with vasomotor symptoms, such as hot flushes and night sweats. Other unpleasant symptoms, urogenital and psychological symptoms, were also evaluated. MATERIAL AND METHOD: Patients were enrolled voluntarily and randomly received 50 mg or 100 mg of Pueraria mirifica in capsules, once daily for six months. RESULTS: Of the 48 enrolled patients, 11 cases were excluded for failing to complete the initial work-up. Thirty-seven cases were evaluated. 20 of 37 (54.1%) randomly received a dose of 50 mg/day of Pueraria mirifica (Group A), and 17 of 37 (45.9%) received 100 mg/day of Pueraria mirifica (Group B). The mean of the modified Greene climacteric scale decreased from 35.6 to 26.6, 17.2 and 15.1 in group A, while group B, declined from 32.6 to 21.0, 14.8 and 13.6 at 1-, 3- and 6-month respectively. The mean serum estradiol, fluctuated from the baseline of 76.6 to 55.4, 56.7, 72.5, 69.2, 114.2 and 74.5 pg/ml at 1-, 2-, 3-, 4-, 5- and 6-month respectively. Whereas the mean serum follicle-stimulating hormone (FSH)/luteinizing hormone (LH) was stable in the range of; 27.1/12.6, 28.3/12.9 and 22.5/11.4 mIU/ml at baseline, 3- and 6-month respectively. CONCLUSIONS: Pueraria mirifica, containing phytoestrogens, relatively alleviated the climacteric symptoms in perimenopausal women. The transient negative profiles occurred in a small number of subjects that included anemia, and liver profiles. While there was a slight decrease in lipoproteins and an increase in hormonal profiles, Pueraria mirifica demonstrates great promise in the treatment of climacteric symptoms among perimenopausal women. However, optimal doses should be clinically assessed, to meet appropriate individual responses.

Estrogen affects vascular tone differently according to vasoactive substances in ovariectomized Sprague-Dawley rat

The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.

Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s) in bradykinin vasodilation

The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasodilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation is reviewed. It has become firmly established that in most species vasodilation in response to bradykinin is mediated by the release of endothelial relaxing factors following the activation of B2-receptors. Although in some cases the action of bradykinin is entirely mediated by the endothelial release of nitric oxide (NO) and/or prostacyclin (PGI2), a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI2 factor accounts for bradykinin-induced vasodilation in a wide variety of perfused vascular beds and isolated small arteries from several species including humans. Since the effect of the non-NO/PGI2 endothelium-derived relaxing factor is practically abolished by disrupting the K+ electrochemical gradient together with the fact that bradykinin causes endothelium-dependent hyperpolarization of vascular smooth muscle cells, the action of such factor has been attributed to the opening of K+ channels in these cells. The pharmacological characteristics of these channels are not uniform among the different blood vessels in which they have been examined. Although there is some evidence indicating a role for KCa or KV channels, our findings in the mesenteric bed together with other reports indicate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hyperpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agonists for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO/PGI2-independent endothelium-dependent vasodilation induced by BK is unlikely to involve a cytochrome P450 arachidonic acid metabolite or an endocannabinoid agonist.

Aspectos reciente en la fisiopatología de la hipertensión arterial / New aspects in the physiopathology of arterial hypertension

En este trabajo analizamos los conocimientos recientes sobre los diversos mecanismos que se han relacionado con la fisiopatología de la hipertensión arterial esencial, su relación con el daño orgánico, principalmente aterosclerótico, las bases para tratamientos más específicos en el futuro, y la posibilidad de correcciones de tales alteraciones con los fármacos disponibles en la actualidad

Efectos sobre la sintomatología climatérica, pérfil lipídico y patrones mamográficos / Effects on climacteric sintomatology, lipid profile and mammography patterns

Se compara dos esquemas de HTR-CC por vía oral con el objeto de evaluar su eficacia clínica, modificaciones del pérfil lipídico y de los patrones mamográficos. Estudio prospectivo, doble ciego de 12 meses de duración en mujeres con sintomatología climatérica, amenorrea mayor que 6 meses y prueba de progesterona negativa. Se evalúa 78 mujeres que completaron el estudio, divididas en dos grupos: grupo A (n= 41) que recibió diariamente 2 mg de estradiol (E2) oral más 2,5 mg de medroxiprogesterona acetato (MPA) y el grupo B: 2 mg de estradiol (E2) más 5 mg de MPA. Ambos grupos terapéuticos demostraron similar eficacia en la disminución de los síntomas vasomotores (SVM) con una reducción del 92 por ciento y del 93 por ciento, respectivamente (p< 0,001); de los síntomas urogenitales: 84 por ciento en ambos grupos (p< 0,01) y de los síntomas funcionales: 75 por ciento en ambos grupos (p< 0,01). El colesterol total disminuyó 12,04 por ciento en el grupo A (p< 0,001) y 7,06 por ciento en el B (p< 0,05), siendo su descenso más significativo en el grupo A, con menor dosis de MPA. El HDL-colesterol aumentó significativamente en ambos grupos, en forma marcada en el grupo A: 12,3 por ciento (p< 0,001) que en el B: 8,5 por ciento (p< 0,05). Los niveles de triglicéridos no experimentaron cambios significativos. Al ingreso un 37,2 por ciento de las mujeres, en forma global, tenía elevado el índice de riesgo cardiovascular (> 5), el número de mujeres con factor de riesgo disminuyó al 7,7 por ciento después de los doce meses de terapia. Un 56 por ciento en el grupo A y un 40,6 por ciento en el grupo B presentaron un leve a moderado aumento de la densidad mamaria, las restantes mujeres no experimentaron modificaciones de sus patrones mamográficos. Ambos esquemas demostraron similar eficacia en el control de la sintomatología climatérica, independientemente de la dosis de MPA empleada. El agregado de MPA continua, no contrarrestó los efectos beneficiosos del E2 sobre el colesterol total y el HDL-colesterol, si bien los resultados fueron mejores al utilizar la dosis más baja de 2,5 mg

Comparison of gastric mucosal blood flow in normal subjects and in patients with portal hypertension using endoscopic laser-Doppler velocimetry.

OBJECTIVE: To compare gastric mucosal blood flow (GMBF) in normal subjects with that in patients with portal hypertension with or without portal hypertensive gastropathy (PHG). METHODS: GMBF was measured by endoscopic laser-Doppler velocimetry in 20 gastroscopically normal subjects and 30 patients with portal hypertension with or without PHG. The effects of breath-holding (vasomotor reflex), submucosal epinephrine and sublingual isosorbide dinitrate were also studied. RESULTS: In normal subjects, GMBF on the greater curvature was (mean +/- SD) 9.5 +/- 1.3 V and on the lesser curvature, 9.1 +/- 1.9 V. Breath-holding caused a reduction in GMBF by 57.1 +/- 13.7%, submucosal epinephrine reduced it by 41.5 +/- 21.5% and sublingual isosorbide caused a rise of 25.8 +/- 15.2%. The GMBF on the greater and lesser curvature respectively in patients with mild PHG (7.7 +/- 1.2 V and 7.7 +/- 0.8 V) and those with severe PHG (6.5 +/- 3.5 V and 6.3 +/- 2.2 V), was significantly less than that in normal subjects (p < 0.05 and p < 0.001 respectively). Vasomotor reflex was blunted in patients with mild and severe PHG (23.3% +/- 20.3 and 23.1% +/- 17.7 respectively, p < 0.001). Responses to submucosal epinephrine and sublingual isosorbide were similar to those recorded in normal subjects. CONCLUSIONS: Patients with portal hypertension have significantly reduced GMBF and significantly attenuated vasomotor reflex in the gastric vascular bed as compared to normal subjects.

Heterogeneity of vascular response to acetylcholine along the human coronary artery

This study included 25 patients with mild CAD. A single coronary artery was selectively studied in each patient. From the biplane image, the images that optimized the projection were chosen for analysis. An automatic edge detection routine was utilized to determine vessel diameters which was divided into segments. Results showed that the mean change in vessel diameter was -0.036 + 0.011 mm upon infusion of Ach 10 - 6 M, -0.74 + 0.013 mm upon infusion of Ach 10 - 5 M and -5.86 + 0.91%, respectively, [all means SEM]. These mean value are comprised of individual segments which have disparate response to Ach. A heterogeneous pattern of response was seen in 20 patients at the Ach 10 - 4M, in 16 patients at the 10-5 M and in 18 patients at the 10-6 dose

Vascular rings in Saudi children: a report of three cases

Three children with vascular ring malformation were seen at the King Fahad Heart Center, Jeddah, between 1981 and 1989, out of a total of 1,500 children with congenital cardiac anomalies, representing an incidence rate of 0.2%. All three patients had a history of respiratory stridor and feeding difficulties since birth. One of the three patients had a double aortic arch, and the other two patients had an aberrant right subclavian artery. We present the surgical management and the outcome in these patients with this rare vascular anomaly

Efectos del diazepam sobre la respuesta vasomotora al CO2 en el hipertenso esencial / Effects of Diazepan upon hipertensive vasomotor response to carbon dioxide(CO2)

Los ansiolíticos constituyen drogas habituales en el tratamiento del paciente hipertenso, sobre todo esencial. Un nutrido grupo de investigadores coinciden en que estos enfermos existe una hiperreactividad de los centros simpáticos relacionados con el control de la presión arterial media. En trabajos anteriores hemos demostrado el efecto del CO2 exitando el centro vasomotor aumentando el tono vasocontrictor simpático en estos pacientes. En este trabajo hemos comparado los efectos que produce la administración de una droga ansiolítica (Diazepam) sobre la respuesta vasomotora al CO2, en un grupo de enfermos con hipertensión ligera y otros en individuos sanos usados como control. Se compara además la acción de la droga con la de un placebo usando el método de doble ciego. En los resultados se puede apreciar que la administración de tales drogas modifica la respuesta vasomotota al CO2 para uno y otro grupo, pero el efecto del ansiolítico es significativamente mayor. Resalta el hecho de que las modicaciones en el sujeto hipertenso son totalmente diferentes a las del individuo normal. Se concluye que la disminución del estrés causa efectos diferentes en el individuo hipertenso, y que la prueba de respiración en circuito cerrado permite predecir la respuesta que tendrá el paciente ante la administración de un ansiolítico

Estudio de las acciones farmacológicas del trinitrato de glicerilo: efecto sobre el consumo de oxígeno miocárdico / Animal pharmacology of gliceryl trinitrate effect on myocardial oxygen uptake

Se estudio la acción de la nitroglicarina sobre el consumo de oxígeno del tejido cardiaco de rata mediante la técnica manométrica de Warburg en cortes ventriculares inmersos, en los que cada muestra fue su propio control. Se hizo determinación del consumo de oxígeno tisular (previa absorción y eliminación del CO2) durante la primera hora del experimento al final de la cual se agregó la nitroglicerina (1.47x10-3,2.35x10-4 y 3.77 x 10-5 M). La nitroglicerina disminuyó el consumo de oxígeno miocárdico en forma significativa (p<0.005 y p <0.0005) y el análisis de varianza de los resultados indicaron que los cambios en el consumo de oxígeno tisular fueron debidos a la nitroglicerina; sin embargo, no se pudo establecer una relación entre la magnitud de la respuesta y las dosis de la sustancia de prueba.

Tratamiento de la impotencia coeundi con sustancias vasoactivas / Treatment of erectile impotence with vasoactive substances

Se define la impotencia coeundi o disfunción erectiva y se señala que obedece a causas psicogénicas o orgánicas. Entre estas últimas, que para algunos autores explican hasta el 80% de los casos, destacan la diabetes tipo I y II; la hipertensión arterial y la arterioesclerosis; el alcoholismo y el tabaquismo; los traumatismos y la cirugía perineal, etc. Se menciona la importancia de algunos neurotransmisores y entre ellos del VIP, en el mecanismo de la erección al relajar la musculatura lisa del tejido cavernoso. Se señalan los promisorios resultados alcanzados, hasta ahora, con el procedimiento de "prótesis farmacológica" basado en la inyección intracavernosa de medicamentos vasodilatadores y en particular de papaverina. Si el tiempo confirma los resultados preliminares, este procedimiento reducirá las indicaciones de las prótesis peneanas y de las operaciones de revascularización

Actions of glucagon on the perfused vessels of the isolated rabbit ear.

Actions of glucagon on the perfused vessels of the isolated rabbit ear were investigated. The two main actions of glucagon on the perfused ear vessels of the rabbit are: (i) release of noradrenaline which accounts for the constrictor response in low tone preparations. The response depends on the level of 3, 5 AMP. If the level rises as a result of noradrenaline action, contriction sets in. (ii) Glucagon may stimulate the adenylcyclase. In the high tone preparation 3,5 AMP levels are probably high. Release of noradrenaline by glucagon would have little additonal effect.