Treatment of the cardiovascular remodeling in hypertensive patients

El corazón del hipertenso se adapta al aumento de sobrecarga que la elevación de las resistencias vasculares sistémicas conlleva aumentando del grosor de la pared ventricular. Los miocitos cardíacos adultos no proliferan, por lo que la hipertrofia cardíaca conlleva un aumento del volumen de las células musculares. Además, aparece hipertrofia e hiperplasia de los componentes non-miocitarios cardíacos. El resultado es una fibrosis perivascular e intersticial que dísminuye la dístensibilidad ventricular y ocluye los vasos coronarios, dísminuye la reserva coronaria y facilita la isquemia miocárdíca. La estructura vascular también se modifica en respuesta al aumento del estrés de la pared arterial, aumentando el cociente pared/luz vascular consecuencia de un aumento del grosor de la pared vascular o del remodelado de los componentes celulares y no celulares de la misma. Estos cambios aumentan la reactividad vascular y potencien el aumento de las resistencias vasculares periféricas caracteristico del hipertenso. La pobre correlación existente entre reducción de la presión arterial y la magnitud del remodelado cardíovascular confirma el importante papel de factores no-hemodínámicos en su patogenia (estimulación de los receptores ATI y al- adrenérgicos, edad, sexo, raza, factores genéticos, etc.). Estudíos experimentales y clínicos han demostrado que todos los antihipertensivos previenen o revierten la hipertrofia cardíaca. Sin embargo, no sólo existen díferencias entre los dístintas familias de fármacos, sino también entre los miembros de cada una de ellas. Los fármacos que inhiben el tono simpático y el sistema renina-angiotensina-aldosterona o reducen la [Ca]i son lo que mayor regresión producen, aunque el efecto parece ser más marcado con los inhibidores de la enzima de conversión. La activación refleja neurohumoral reducida por diuréticos o vasodilatadores arteriales podria explicar su incapacidad para revertir el remodelado cardiovascular a pesar de que normalizan la presión arterial. Es lógico, por tanto, sugerir que el futuro desarrollo de fármacos antihipertensivos debe ir dirigido no sólo a obtener fármacos capaces de revertir el proceso de remodelado cardíovascular del hipertenso, es decir, conseguir restaurar la estructura y función de los órganos díana. Sólo de esta forma podremos reducir la morbiortalidad del hipertenso.The heart adapts to increasing afterload, such as that which occurs in arterial hypertension with an increase in wall thickness (left ventricular hipertrophy) in order to bring wall stress back to normal. Adult cardiac myocytes are unable to proliferate, so that myocyte hypertrophy is the hallmark of left ventricular hipertrophy. Cardiac remodelling, however, involves not only myocyte growth but also hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. The result is a perivascular and intersticial fibrosis that impair myocardial stiffuess. In response to increased arterial pressure, the vessel structure is altered such that the ratio of the width of the wall to the width of the lumen is increased by either an increase in mass or rearrangements of vascular smooth muscle cells and other cellular and noncellular elements of the vascular wall. These changes increased vascular reactivity, potentiated the increase in peripheral vascular resistance characteristic of hypertension and attenuated the coronary reserve to ischemic provocation. The poor correlation between blood pressure and the magnitude of cardiovascular remodelling strongly suggests a role for nonhemodynarnic factors in its pathogenesis (i.e. neurohumoral activation, neurogenic stimuli, genetic predisposition, gender, age and race). An increase in sympathetic (cd-adrenoceptors) and renin-angiotensin-aldosterone systerns (ATl receptors) piay an important role in both cardiac myocyte and nonmyocyte growth and remodelling. Experimental and clinical studies have demonstrated that all antihypertensive agents may prevent or cause regression of cardiovascular remodelling. However, despite their equipotent blood-lowering effects, there are not only marked differences in the ability of different types of antihypertensive drugs to prevent or reverse cardiovascular remodelling but also whithin the same class of pharmacological drugs. Antihypertensive drugs that modulate the sympathetic or renin-angiotensin-aldosterone systems or the intracellular free Ca concentration can reverse cardiovascular remodelling, this effect being more pronounced with ACE inhibitors. Reflex neurohumoral activation may be responsible for the failure of sorne antihypertensive drugs to produce regress cardiovascular remodelling (diuretics, vasodilators, ~-blockers with intrinsic sympathomirnetic activity and dihydropyridines), even through they reduce arterial blood presure to normotensive levels. It is therefore, logical to suggest that a more ambitious approach to modem treatrnent of hypertension would not only be to reduce elevated blood pressure, but also to introduce an important additional goal, namely to attain regression of structurally remodelled heart and vasculture to, or toward, normal structure and function. Only this therapeutic approach might truly reduce the risk of cardiovascular complications in the hipertensive patient

Tratamiento de la insuficiencia cardíaca

La insuficiencia cardíaca congestiva (lCC) puede definirse como la incapacidad del corazón para proveer las necesidades tisulares y/o la necesidad de mantener unas presio nes de llenado ventricular anormalmente elevadas para producir un volumen minuto adecuado. Los objetivos del tratamiento de la ICC incluyen la mejoría de los síntomas y la limitación de la actividad física, prevenir la progresión del proceso y prolongar la supervivencia. Clásicamente hay dos formas de tratamiento: aumentar la contractilidad cardiaca y disminuir la pre y postcarga. Los diuréticos constituyen la primera línea de tratamiento en la mayoría de los pacientes con ICC sintomática ya que producen una mejoría rápida y mantenida de los síntomas que, en su mayoría, son consecuencia de la retención hidrosalina que se manifiesta como edemas y congestión pulmonar. La digoxina, el único fármaco inotrópico positivo utilizado por vía oral, no sólo bloquea la ATPas-Na/ K, sino que además restaura la sensibilidad de los barorreceptores e inhibe el tono simpático. Por el contrario, los inhibidores de la fosfodiesterasa aumentan la indicencia de arritmias, aceleran la progresión del cuadro y disminuyen la supervivencia del pacien te. La utilización de vasodilatadores se basa en su capacidad para mejorar la función ventricular actuando sólo sobre el componente vascular, reduciendo la precarga y/o la postcarga. Los inhibidores de la enzima de conversión interfieren con la activación neurohumoral que conlleva a la vaso constricción y la retención hidrosalina y reduce la supervivencia. Asociados a diuréticos y digoxina mejoran la situación clínica y hemodinámica y aumentan la supervivencia

Correlation functions in scalar field theory at large charge

We compute general higher-point functions in the sector of large charge operators ϕn,ϕ¯¯¯n at large charge in O(2) (ϕ¯¯¯ϕ)2 theory. We find that there is a special class of "extremal" correlators having only one insertion of ϕ¯¯¯n that have a remarkably simple form in the double-scaling limit n →∞ at fixed g n2 ≡ λ, where g ~ ϵ is the coupling at the O(2) Wilson-Fisher fixed point in 4 − ϵ dimensions. In this limit, also non-extremal correlators can be computed. As an example, we give the complete formula for ⟨ϕ(x1)nϕ(x2)nϕ¯¯¯(x3)nϕ¯¯¯(x4)n⟩, which reveals an interesting structure

Mise au point d'une méthode d'extraction des lipides solubles totaux, des glucides solubles totaux et des composés phénoliques solubles totaux des organes de la vigne

Il est possible d'obtenir très rapidement et à partir d'une même poudre la totalité des lipides solubles, des glucides solubles et des composés phénoliques solubles. Le nombre d'opération nécessaires dépend des organes et a été déterminé pour les rameaux principaux, les feuilles, les rafles, les baies et les pépins.Adjustment of a method of extraction of total soluble lipids, total soluble carbohydrates and total soluble phenolic compounds from the organs of the vineIt is possible to obtain very quickly from the same powdered plant material total amounts of soluble lipids, soluble carbohydrates and soluble phenolic compounds. The number of operations required depends upon the organ concerned and has been determined for the fruiting shoots, the leaves, the rachises, the berries and the seeds

Multiple polaron quasiparticles with dipolar fermions in a bilayer geometry

We study the Fermi polaron problem with dipolar fermions in a bilayer geometry, where a single dipolar particle in one layer interacts with a Fermi sea of dipolar fermions in the other layer. By evaluating the polaron spectrum, we obtain the appearance of a series of attractive branches when the distance between the layers diminishes. We relate these to the appearance of a series of bound two-dipole states when the interlayer dipolar interaction strength increases. By inspecting the orbital angular momentum component of the polaron branches, we observe an interchange of orbital character when system parameters such as the gas density or the interlayer distance are varied. Further, we study the possibility that the lowest energy two-body bound state spontaneously acquires a finite center of mass momentum when the density of fermions exceeds a critical value, and we determine the dominating orbital angular momenta that characterize the pairing. Finally, we propose to use the tunneling rate from and into an auxiliary layer as an experimental probe of the impurity spectral function.Comment: 19 pages, 18 figures. Accepted versio

The Cerebellar Nodulus/Uvula Integrates Otolith Signals for the Translational Vestibulo-Ocular Reflex

Background: The otolith-driven translational vestibulo-ocular reflex (tVOR) generates compensatory eye movements to linear head accelerations. Studies in humans indicate that the cerebellum plays a critical role in the neural control of the tVOR, but little is known about mechanisms of this control or the functions of specific cerebellar structures. Here, we chose to investigate the contribution of the nodulus and uvula, which have been shown by prior studies to be involved in the processing of otolith signals in other contexts. Methodology/Principal Findings: We recorded eye movements in two rhesus monkeys during steps of linear motion along the interaural axis before and after surgical lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye velocity during constant-velocity motion but had only a small effect on the response to initial head acceleration. We fit eye velocity to a linear combination of head acceleration and velocity and to a dynamic mathematical model of the tVOR that incorporated a specific integrator of head acceleration. Based on parameter optimization, the lesion decreased the gain of the pathway containing this new integrator by 62%. The component of eye velocity that depended directly on head acceleration changed little (gain decrease of 13%). In a final set of simulations, we compared our data to the predictions o

Electroreflectance spectroscopy in self-assembled quantum dots: lens symmetry

Modulated electroreflectance spectroscopy $\Delta R/R$ of semiconductor self-assembled quantum dots is investigated. The structure is modeled as dots with lens shape geometry and circular cross section. A microscopic description of the electroreflectance spectrum and optical response in terms of an external electric field (${\bf F}$) and lens geometry have been considered. The field and lens symmetry dependence of all experimental parameters involved in the $\Delta R/R$ spectrum have been considered. Using the effective mass formalism the energies and the electronic states as a function of ${\bf F}$ and dot parameters are calculated. Also, in the framework of the strongly confined regime general expressions for the excitonic binding energies are reported. Optical selection rules are derived in the cases of the light wave vector perpendicular and parallel to $$. Detailed calculation of the Seraphin coefficients and electroreflectance spectrum are performed for the InAs and CdSe nanostructures. Calculations show good agreement with measurements recently performed on CdSe/ZnSe when statistical distribution on size is considered, explaining the main observed characteristic in the electroreflectance spectra

Antiarrhythmic agents

Los fármacos antiarritmicos son un grupo heterogéneo de sustancias que constituyen, junto con la estimulación eléctrica programada, la implantación de marcapasos, la cirugía y la fulguración, la base de la terapéutica antiarritmica actual. La mayor parte de las arritmias observadas en la práctica clinica son debidas al fenómeno de reentrada, que representa una alteración en la conducción del impulso cardiaco. Para que se produzca una arritmia por reentrada debe: a) existir un obstáculo anatómico o funcional que defina el circuito de reentrada, b) existir un área de bloqueo unidireccional y c) el tiempo que el impulso tarda en recorrer el circuito debe ser mayor que el período refractario. Teóricamente, estas arritmias pueden ser tratadas mediante dos tipos diferentes de maniobras: 1) disminuyendo la velocidad de conducción, de tal manera que convirtamos el área de bloqueo unidireccional en bidireccional. Los fánnacos antiarritmicos que producen este efecto son aquellos que actúan inhibiendo la corriente rápida de entrada de sodio (INa), o fánnacos antiarritmicos del grupo 1. 2) Prolongando el período refractario, de tal modo que el frente de onda del circuito se encuentre con tejido inexcitable. Recientes estudios clínicos (CAST, 1989) han puesto en tela de juicio la eficacia de los fánnacos antiarrítmicos del grupo 1, dado que dos de los fánnacos más potentes de este grupo (flecainida y encainida) no sólo no disminuyeron, sino que aumentaron la mortalidad en pacientes con infarto de miocardio previo y que presentaban más de 7 extrasístoles ventriculares tempranos. Estos resultados obligaron a un replanteamiento en la terapéutica antiarritmica, y condujo a diferentes grupos de investigación a la síntesis y caracterización de nuevos fármacos capaces de prolongar el periodo refractario, o fármacos antiarritmicos del grupo m. El fármaco antiarritmico "ideal" de este grupo sería aquél que produjera una mayor prolongación del período refractario a frecuencias de estimulación más rápidas (más efectivo en taquicardia). Sin embargo, ningún fármaco antiarritmico del grupo m presenta este perfil farmacológico. Por el contrario, son más eficaces a frecuencias lentas (durante la bradiacardia) que a frecuencias rápidas. La excepción es la arniodarona (el primer fánnaco antiarritmico de este grupo, con propie dades antiarritmicas del grupo 1, B-bloqueantes y antagonistas del calcio) que prolonga el período refractario a cualquier frecuencia de estimulación: es independiente de la frecuencia. La utilización de técnicas de Biología Molecular que nos permitan conocer la estructura de los canales iónicos involucrados en la r epolarización del potencial de acción, así como estudios realizados en miocitos cardiacos humanos nos proporcionarán una gran ayuda para diseñar nuevos fánnacos antiarritmicos sobre bases más racionales.Antiarchythmic agents are a very hoterogenous group of drugs which, together with programmed electrical stimulation, pacemaker implantation, ablation and surgery, constitute the basis of the antiarrhythmic therapy. Most clinical arrhythmias are due to reentry, which represents an alteration of the cardiac impulse. The basis for reentry are: a) an anatornical or functional obstacle which defines the circus movement, b) an area of unidirectional block, and c) the length of path must exceed the wave length deterrnined by effective refractoriness. Theoretically, reentrant arrhythmias can be suppressed by: 1) decreasing the conduction velocity, so that the area of unidirectional block becomes an area or bidirectional block. Antiaarrhythmic drugs acting by this mechanism include those that decrease the fast inward sodium current (INal), the so-caHed class 1 antiarrythmic drugs. 2) Lengthenin of the effective refractory period, in such a way that the wavefront encroaches in its own refractory period and the cardiac impulse cannot be propagated anymore. Drugs that selectively prolonged the effective refractory period are included as class III antiarrhytmics. Recent clinical studies (CAST, 1989) have warned the scientific community about the effectiveness and safety of class 1 antiarrhythmic drugs, since two of them (flecainide and encainide) did not de crease, but increased mortality in patients which previous myocardial infarction and asymptomatic ventricular extrasystoles. These results led numerous work groups and pharmaceutical companies to develop new class III antiarrhythmic drugs. The "ideal" class III antiarrhythmic drug would be that which produced rninirnal effect in sinus rhythm but produced a marked prolongationof the effective refractory period when the heart rate increased (i.e. during tachycardia). However, none of the available class III antiarrhythmic drugs exhibit this pharrnacological profile. On the contrary, they prolonged cardiac refractoriness more at low frequencies of stimulation (bradycardia) than at higher stimulation rates. Only arniodarone, the first class ID antiarrhythmic drug, which exhibits class 1, 11 (B-adrenoceptor blockade) and IV (calcium antagonist) properties produced a prolongation of the effective refractory period at aH cardiac rates, i.e. its effect is frequency-independent. The use of Molecular Biology techniques which allow us to determine the structure of the ionic channels involved in the repolarization of the cardiac action potential, as well as the studies performed in isolated human cardiac myocytes will afford the basis for a more rational design of new antiarrhythmic drugs