Publication: Estudio de la función endotelial de los fármacos oxitócicos en la prevención de la hemorragia posparto. Mecanismo de acción de la endotelina y óxido nítrico
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2018-04-06
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Universidad Complutense de Madrid
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Abstract
La hemorragia posparto (HPP) es considerada como causa aislada más importante de mortalidad materna a nivel mundial. El sangrado excesivo tras el parto puede ocurrir hasta en un 19,8% de los casos provocando una morbi-mortalidad importante. La causa más frecuente de HPP es la atonía uterina. Por tanto, en el manejo del parto debemos prevenir dicha situación con diferentes maniobras obstétricas de prevención, entre las que se incluyen los fármacos oxitócicos que actúan aumentando la contractilidad uterina. Conocemos muy bien el mecanismo de acción que ejerce la oxitocina sobre los receptores de oxitocina (OT) de la fibra muscular lisa uterina, que se traduce básicamente en un incremento de las contracciones rítmicas y del tono miometrial. Sin embargo, los receptores OT no sólo están presentes en el músculo uterino, sino que se localizan en otros territorios muy variados, sitios recientemente descritos como en las células tumorales de diversos tejidos, células óseas, mioblastos, cardiomiocitos y células endoteliales. Entre ellos, el que más nos interesa conocer dentro de la indicación de la oxitocina como fármaco uterotónico en la prevención de la hemorragia posparto es la capa muscular lisa de los vasos sanguíneos. Esta función podría añadir a la acción de la oxitocina, más allá de su papel clásico de inductor de las contracciones uterinas, una acción vasoconstrictora. La aparición de un nuevo fármaco oxitócico, la carbetocina, nos amplía la perspectiva de esta hipótesis y por tanto del estudio, pues además de verificar esta acción endotelial de los oxitócicos mediante un elemento adicional, nos permitirá evaluar la potencia farmacológica al poder comparar esta acción entre los dos fármacos disponibles en la actualidad. El óxido nítrico y la endotelina representan los marcadores bioquímicos que nos permiten evaluar la función vascular. Las variaciones de los niveles séricos de estos marcadores en relación a la administración de fármacos oxitócicos nos permitirá definir de una manera más aproximada el efecto vascular de la oxitocina y la carbetocina...
Postpartum hemorrhage (PPH) has been considered the main cause of maternal death worldwide. Excessive bleeding after delivery may occur as much as 19,8% of cases, resulting in an important morbidity and mortality. Uterine atony is the first cause of PPH. Therefore, in the management of the delivery; we must employ different obstetric strategies for hemorrhage prevention, one of them, prophylactic treatment with oxytocic agents for an effective constrictive action on the uterus. The mechanisms of action of oxytocin on the oxytocin receptor of the smooth muscle are well known. It is based on the increase of rhythmic contractions and uterine tone. However, oxytocin receptor is not only present in the smooth muscle, can also be located in many other different territories, some of them recently described such as tumoral cells of diverse tissues, bone cell, myoblast, cardiomyocites and endothelial cells. Among these different receptors, the one most interesting for us in the indication of oxytocin as uterotonic agent in the postpartum hemorrhage is the smooth muscle of blood vessels. This function could add to the classic action of the oxytocin a mechanism of vasoconstriction. The emerging of a new oxytocic agent, carbetocin, allow us to extend the prospect of this hypothesis and therefore of this study. In addition to verifying the endothelial action of oxytocic agents with an additional agent, it may permit us to evaluate the pharmacological potency through the comparison of this action between the two oxytocic agents available at the moment. Nitric oxide and endotelin represents biochemical markers that enable us the vascular function evaluation. The serum levels variation of these markers with regard to the administration of the oxytocic agents will allow us to define more accurately the vascular effect of oxytocin and carbetocin...
Postpartum hemorrhage (PPH) has been considered the main cause of maternal death worldwide. Excessive bleeding after delivery may occur as much as 19,8% of cases, resulting in an important morbidity and mortality. Uterine atony is the first cause of PPH. Therefore, in the management of the delivery; we must employ different obstetric strategies for hemorrhage prevention, one of them, prophylactic treatment with oxytocic agents for an effective constrictive action on the uterus. The mechanisms of action of oxytocin on the oxytocin receptor of the smooth muscle are well known. It is based on the increase of rhythmic contractions and uterine tone. However, oxytocin receptor is not only present in the smooth muscle, can also be located in many other different territories, some of them recently described such as tumoral cells of diverse tissues, bone cell, myoblast, cardiomyocites and endothelial cells. Among these different receptors, the one most interesting for us in the indication of oxytocin as uterotonic agent in the postpartum hemorrhage is the smooth muscle of blood vessels. This function could add to the classic action of the oxytocin a mechanism of vasoconstriction. The emerging of a new oxytocic agent, carbetocin, allow us to extend the prospect of this hypothesis and therefore of this study. In addition to verifying the endothelial action of oxytocic agents with an additional agent, it may permit us to evaluate the pharmacological potency through the comparison of this action between the two oxytocic agents available at the moment. Nitric oxide and endotelin represents biochemical markers that enable us the vascular function evaluation. The serum levels variation of these markers with regard to the administration of the oxytocic agents will allow us to define more accurately the vascular effect of oxytocin and carbetocin...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Obstetricia y Ginecología, leída el 20/10/2014