Inotropic activity induced by carbamazepine-alkyne derivative in an isolated heart model and perfused to constant flow Actividad inotrópica inducida por el derivado carbamacepina-alquino en un modelo de corazón aislado y perfundido a flujo constante

Introduction. Few data exist with respect to the effects of carbamazepine and its derivatives at cardiovascular level; furthermore, the molecular mechanisms and cellular site of action are still unclear. Objective. The effects induced by carbamazepine-alquine derivative on perfusion pressure, vascular resistance and left ventricular pressure were evaluated. Materials and methods. The effects of carbamazepine and carbamazepine-alquine on the perfusion pressure, vascular resistance and left ventricular pressure were examined in isolated rat hearts (Langendorff model). Results. Four results were obtained: (1) The carbamazepine-alquine derivative [10-9 mM] increased the perfusion pressure and vascular resistance in comparison with the carbamazepine [10-9 mM]; (2) the effect of carbamazepine-alquine derivative [10-9-10-4 mM] on left ventricular pressure not was inhibited by metoprolol or prazosin at a dose of 10-6 mM; (3) nifedipine [10-6 mM] blocked the effects exerted by the carbamazepine-alquine derivative [10-9-10-4 mM] on left ventricular pressure, and (4) the carbamazepine-alquine derivative at dose of 10-9 mM increased the concentration of intracellular calcium over a time period of 3-18 min; nevertheless, in presence of nifedipine [10-6 mM] this effect was inhibited significantly (p=0.005). Conclusions. The activity exerted by carbamazepine-alquine derivative on perfusion pressure, vascular resistance and left ventricular pressure involved activation of calcium channel type-L, brought indirectly changes in the intracellular calcium levels and subsequently induced a positive inotropic effect. Introducción. Existen pocos datos con respecto a los efectos de la carbamacepina y sus derivados en el aparato cardiovascular; además, el mecanismo molecular y su sitio de acción celular no son claros. Objetivo. Evaluar los efectos inducidos por el derivado carbamacepina-alquino sobre la presión de perfusión, la resistencia vascular y la presión ventricular izquierda. Materiales y métodos. Los efectos de la carbamacepina y del derivado carbamacepina-alquino sobre la presión de perfusión, la resistencia vascular y la presión ventricular izquierda fueron evaluados en un modelo de corazón aislado de rata (Langendorff). Resultados. Se encontró que: 1) el derivado carbamacepina-alquino (1x10-9 mM) incrementa la presión de perfusión y la resistencia vascular en comparación con la carbamacepina (1×10-9 mM); 2) los efectos del derivado carbamacepina-alquino (1×10-9-1×10-4 M) sobre la presión intraventricular no fueron inhibidos por metoprolol o prazosina (1×10-6 mM); 3);