Citoprotección miocárdica: efecto de la trimetazidina en la isquemia miocárdica

RESUMEN El objetivo del presente trabajo ha sido evaluar la acción de la trimetazidina (TMZ), un fármaco antiisquémico con un mecanismo de acción metabólico, en el deterioro de la función sistólica y en las alteraciones mitocondriales que se producen en el miocardio sometido a isquemia-reperfusión. Para ello se han utilizado 30 perros mestizos, de ambos sexos, distribuidos en 2 protocolos diferentes de isquemia-reprfusión: 1) un protocolo de 20 obstrucciones completas de la arteria coronaria descendente anterior (DA) de 2 minutos de duración y separadas por 3 minutos de reperfusión; y 2) un protocolo de obstrucción única de una rama distal de la DA, de 15 minutos de duración y seguida de 60 minutos de reperfusión. Dentro de cada protocolo isquémico, los animales fueron randomizados, a doble ciego, a tratamiento con Placebo o TMZ, a dosis de 50 mg a las 8:00 horas y 75 mg a las 15:00 horas. Tras una semana de tratamiento, se les aplicó el protocolo isquémico descrito anteriormente. Las variables analizadas a lo largo de todo el procedimiento han sido: parámetros hemodinámicos (frecuencia cardíaca, presión ventricular izquierda y dP/dt), parámetros de función regional de la zona isquémica y de una zona control (diámetros telesistólico y telediastólico y fracción de acortamiento), niveles de troponina T (basales y al final de la experimentación) y análisis mediante microscopía electronica de las mitocondrias de la zona isquémica y control (estudio cualitativo y cuantitativo). ______________________________________________________________________________________________________ The functional and ultrastructural consequences of the treatment with trimetazidine (TMZ) were analyzed in two canine models of myocardial stunning: One model of very brief coronary occlusion (2 minutes) and repeated (20) followed of 3 minutes of reperfusion (protocol 1), and a 15 minutes long unique ischaemia model and 60 minutes of reperfusion (protocol 2). 30 mestize dogs were used, randomized at double blind, with Placebo treatment or TMZ during a week. The examined end points were: haemodynamic parameters (cardiac rate, left ventricular pressure and dP/dt), parameters of regional function of the ischemic and control myocardial areas (telesystolic and teledyastolic diameter and shortening fraction), and ultrastructual study through electronic microscope of mitochondria (injury and size). During performance of protocol 1, it was detected a lesser damage in the regional function of ischemic area at the end of the testing in the group treated with TMZ (93% of basal value) comparing with the Placebo serie (64% of basal value). In the ultrastructural study of ischemic area, differences were not objectified in the mitochondrial damage between both series, but mitochondrias treated with TMZ showed a significant increase in the perimeter and major axis and a decrease in the minor one. During the analysis of protocol 2, the shortening fraction of the ischemic area experienced a drop of its values to figures of acinesia/discinesia during coronary obstruction, with partial recovery of its values after 60 minutes of reperfusion, without significant differences between Placebo series and TMZ ones (50% vs 41% of basal value). In the ultrastructural study of ischemic area no significant differences were noticed between both series, with similar percentages of mitochondrial damage; on the contrary ischemic mitochondrias in the group treated with TMZ were shorter than those presented in the Placebo group. In the control area do not submitted to ischemia in both protocols, the mitochondrias treated with TMZ showed significant morphology changes, with an increase on major axis and a decrease of the minor one, presenting a morphology like a small cane

Gender differences related to the presence of atrial fibrillation in older hypertensive patients.

AIM: To determine whether there are gender differences in the epidemiological profile of atrial fibrillation(AF) and to characterise the clinical, biochemical, and therapeutic factors associated with AF. METHODS: Each investigator (primary care physicians or physicians based in hospital units for hypertension treatment) recruited the first 3 patients with an ageof ≥ 65 years and a clinical diagnosis of hypertension(ambulatory blood pressure monitoring and an electrocardiogram,were performed) on the first working day of the week for 5 wk and identified those individuals with atrial fibrillation. A binary logistic regression was performed, including all of the variables that were significant in the univariate analysis, to establish the variables that were associated with the presence of arrhythmia.CONCLUSION: In patients with hypertension over 65 years of age, there are relevant gender differences in the factors associated with AF