RESUMO
Las arritmias que aparecen despues de la recirculacion sanguinea de una arteria coronaria previamente obstruida, han sido objeto de estudio de multiples investigadores desde finales de la decada de los 70 hasta nuestros dias, debido a la posibilidad de que estos tipos de trastornos del ritmo cardiaco pueden llevar a la muerte a pacientes en los que se libera un espasmo coronario o se produce la lisis de un trombo coronario. Con el presente trabajo tuvimos la oportunidad de profundizar en el conocimiento fisiopatologico de estas arritmias ventriculares, para ello utilizamos un modelo experimental animal de probada eficacia en este tipo de estudio. En el empleamos tres antiarritmicos clase I: prajmalina, lidocaina y mexiletine con el objetivo de conocer y analizar los efectos de estas drogas sobre la tension arterial, la frecuencia cardiaca y la incidencia de las arritmias por reperfusion coronaria. Nuestra investigacion arrojo una disminucion notable del por ciento de incidencia de arritmias en el grupo de animales tratados con mexiletine a diferencia de los resultados obtenidos con el resto de las series. Tambien en todos los grupos experimentales se registraron hipotension y bradicardia significativas al ser comparadas con su control: se emplearon para este analisis estadistico la "t" de Student para muestras pareadas (p < 0,05)
Assuntos
Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , Lidocaína/farmacologia , Mexiletina/farmacologia , Prajmalina/farmacologia , Coelhos , Reperfusão Miocárdica/métodosRESUMO
The propyl derivative of ajmaline, N-n-propylajamaline (prajmalium), is an antiarrhythmic compound that lacks the commonly reported negative inotropic effects of all others under clinical use. The present study was undertaken to establish and understand its effects at the cellular level in mammalian preparations. Electrical and mechanical activities were recorded from right ventricular strips and Na and L-type Ca currents (INa and ICaL, respectively) were recorded with the whole-cell patch-clamp technique in right ventricular myocytes freshly dissociated from rabbit hearts. Prajmalium decreased the maximal rate of depolarization of the action potential in a dose-dependent manner with an EC50 of 3 microM. This effect was use and frequency dependent. Action potential duration was increased by 1 microM prajamalium but decreased on applying higher concentrations. The force of contraction was slightly (15%) increased at 0.1 microM, not affected at all at 1 microM and depressed by 30% at 20 microM. In single cardiomyocytes maintained at negative holding potentials, INa was slightly depressed by prajmalium at 10 nM and reduced by 75% at 10 microM. ICaL was increased by 30 and 20% on applying prajmalium at 1 and 10 microM, respectively; on the other hand, ICaL was reduced by these two concentrations of prajmalium at less negative holding potentials. A higher prajmalium concentration (100 microM) decreased ICaL at all holding potentials studies and this effect was enhanced with depolarization. The increase in ICaL induced by prajmalium (1 microM) was also observed after ICaL had been fully beta-adrenergic and P2-purinergic stimulated by isoproterenol (1 microM) in the presence of IBMX (100 microM) and ATP (10 microM). It is concluded that prajmalium is able to increase ICaL in rabbit ventricular cells in a voltage-dependent manner, an effect that could account in part for the observed lack of negative inotropism of this antiarrhythmic in clinics.
Assuntos
Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Prajmalina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Eletrofisiologia , Coração/fisiologia , Técnicas In Vitro , Miocárdio/citologia , Coelhos , Sódio/metabolismo , Estimulação QuímicaRESUMO
The effects of N-n-propylajmaline (prajmalium) on the Na and Ca currents of single frog atrial and ventricular cells were studied by means of the whole-cell patch-clamp technique. Prajmalium (10(-9) to 10(-6) M) depressed the Na current (INa) in a dose- and use-dependent manner. In the same range of concentrations, prajmalium induced a dual effect on the high (ICaL) and low (ICaT) threshold Ca currents (the latter being only present in atrial cells). At a low concentration (10(-9) M), prajmalium increased both Ca currents while at high concentrations (10(-6) M) it depressed them. Prajmalium appeared very potent on ICaT although this current is generally reported to be barely sensitive to agonists and drugs. The action of the drug was also accompanied by a shortening in the half-time of inactivation of the Ca currents and a slight hyperpolarizing shift of their availability curves. The increase in ICaL by prajmalium was not prevented by prazosin (10(-7) M) nor by propranolol (10(-6) M), and it was also observed after ICaL had been fully stimulated by isoproterenol (10(-7)M). Nifedipine (10(-6) M), however, was able to prevent or block the prajmalium-induced increase in ICaL. Some similarities between the actions of prajmalium and dihydropyridine agonists on Ca currents are discussed.
Assuntos
Cálcio/metabolismo , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Prajmalina/farmacologia , Animais , Isoproterenol/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Miocárdio/citologia , Nifedipino/farmacologia , Prazosina/farmacologia , Propranolol/farmacologia , Rana catesbeiana , Rana esculenta , Sódio/metabolismoRESUMO
Se estudiaron los efectos del bitartrato de N-propil ajmalina (NPAB, sintetizado en nuestro país), sobre la corriente de sodio (iNa) en células miocárdicas ventriculares. En trabéculas de pared libre de ventrículo derecho de conejo, la velocidad máxima de despolarización (dv/dt máx) se redujo significativamente con el incremento de la dosis de NPAB (de 0,125 a 20 * M) hasta llegar al 60% de inhibición a la dosis máxima. Esto se correspondió con una disminución similar en la densidad de iNa calculada a partir de los planos de fase (dv/dt vs. potencial de membrana). Los efectos sobre la dv/dt máx. mostraron dependencia directa con la frecuencia de estimulación (dependencia del uso). Con la técnica de patch-clamp en células ventriculares aisladas de corazón de rana, se demostró que el NPAB reduce la iNa en forma, no sólo dependiente de la frecuencia, sino tambièn en dependencia del potencial de membrana, pues induce un desplazamiento de 10 mV en la curva de inactivación (o de disponibilidad) hacia potenciales más negativos. La droga, además, enlenteciò el proceso de reactivaciòn de iNa. Se concluye que el NPAB sintetizado en nuestro país, tiene acciones sobre la célula cardiaca que lo pueden clasificar como un antiarrítmico de la clase 1-A