René Asenjo

A Randomized Controlled Trial to Prevent Post-Operative Atrial Fibrillation by Antioxidant Reinforcement

OBJECTIVES This study was designed to assess whether the reinforcement of the antioxidant system, through n-3 fatty acids plus antioxidant vitamin supplementation, could reduce the incidence of post-operative atrial fibrillation. BACKGROUND Therapy to prevent post-operative atrial fibrillation remains suboptimal. Although oxidative stress plays a key role in the pathogenesis of this arrhythmia, antioxidant reinforcement has produced controversial results. METHODS A total of 203 patients scheduled for on-pump cardiac surgery were randomized to placebo or supplementation with n-3 polyunsaturated fatty acids (2 g/day) (eicosapentaenoic acid:docosahexaenoic acid ratio 1:2), vitamin C (1 g/day), and vitamin E (400 IU/day). The primary outcome was the occurrence of post-operative atrial fibrillation. Secondary outcomes were the biomarkers related to oxidative stress and inflammation. RESULTS Post-operative atrial fibrillation occurred in 10 of 103 patients (9.7%) in the supplemented group versus 32 of 100 patients (32%) in the placebo group (p < 0.001). Early after surgery, placebo patients presented with increased levels of biomarkers of inflammation and oxidative stress, which were markedly attenuated by antioxidant supplementation. The activity of catalase, superoxide dismutase, and glutathione peroxidase in atrial tissue of the supplemented patients was 24.0%, 17.1%, and 19.7% higher than the respective placebo values (p < 0.05). The atrial tissue of patients who developed atrial fibrillation showed NADPH oxidase p47-phox subunit protein and mRNA expression 38.4% and 35.7% higher, respectively, than patients in sinus rhythm (p < 0.05). CONCLUSIONS This safe, well-tolerated, and low-cost regimen, consisting of n-3 polyunsaturated fatty acids plus vitamins C and E supplementation, favorably affected post-operative atrial fibrillation, increased antioxidant potential, and attenuated oxidative stress and inflammation. (Prevention of Post-Operative Atrial Fibrillation: Pathophysiological Characterization of a Pharmacological Intervention Based on a Novel Model of Nonhypoxic Pre-Conditioning; ISRCTN45347268).

Antioxidant Therapy Reduces Oxidative and Inflammatory Tissue Damage in Patients Subjected to Cardiac Surgery with Extracorporeal Circulation

Ischaemia reperfusion injury is a pathophysiological event that occurs after cardiac surgery with extracorporeal circulation. This clinical event has been associated with the induction of oxidative and inflammatory damage in atrial tissue. Here, we tested whether combined omega 3 polyunsaturated fatty acids (n-3 PUFA)-antioxidant vitamin protocol therapy reduces oxidative and inflammatory cardiac tissue damage. This trial assigned 95 either-sex patients to supplementation with n-3 PUFA (2 g/day), or matching placebo groups, 7 days before on-pump surgery. Antioxidant vitamins C (1 g/day) and E (400 IU/day) or placebo were added from 2 days before surgery until discharge. Blood and atrial tissue samples were obtained during the intervention. Reduced/oxidized glutathione (GSH/GSSG) ratio, malondialdehyde (MDA) and protein carbonylation were determined in atrial tissue. Leucocyte count and high-sensitivity C-reactive protein (hs-CRP) in blood plus nuclear factor (NF)-κappaB activation in atrial tissue served for inflammation assessment. Lipid peroxidation and protein carbonylation were 27.5 and 24% lower in supplemented patients (p < 0.01). GSH/GSSG ratio was 38.1% higher in supplemented patients compared with placebo (p < 0.01). Leucocyte count and serum hs-CRP levels were markedly lower throughout the protocol in supplemented patients (p < 0.01). Atrial tissue NF-κB DNA activation in supplemented patients was 22.5% lower than that in placebo patients (p < 0.05). The combined n-3 PUFA-antioxidant vitamin protocol therapy here proposed reduced the oxidative stress and inflammation biomarkers, in patients undergoing on-pump cardiac surgery.

Use of vitamins C and E as a prophylactic therapy to prevent postoperative atrial fibrillation.

Oxidative stress has been strongly involved in the underlying mechanism of atrial fibrillation, particularly in the arrhythmia occurring in patients undergoing cardiac surgery with extracorporeal circulation (postoperative atrial fibrillation). The ischemia/reperfusion injury thus occurring in the myocardial tissue contributes to the development of tissue remodeling, thought to be responsible for the functional heart impairment. Consequently, structural changes due to the cardiac tissue biomolecules attack by reactive oxygen and/or nitrogen species could account for functional changes in ion channels, transporters, membrane conductance, cytosolic transduction signals, and other events, all associated with the occurrence of arrhythmic consequences. The lack of success and significant side effects of anti-arrhythmic drugs have given rise to attempts aimed to develop alternative novel pharmacologic treatments. On this line, the biological properties of the antioxidant vitamins C and E suggest that they could decrease the vulnerability of the heart to the oxidative damage. Nevertheless, very few studies to assess their anti-arrhythmic effects have been reported in humans. The clinical and experimental evidence supporting the view that the pharmacological use of antioxidant vitamins could contribute to prevent postoperative atrial fibrillation is presented.

Prevention of atrial fibrillation following cardiac surgery: basis for a novel therapeutic strategy based on non-hypoxic myocardial preconditioning.

Atrial fibrillation is the most common complication of cardiac surgical procedures performed with cardiopulmonary bypass. It contributes to increased hospital length of stay and treatment costs. At present, preventive strategies offer only suboptimal benefits, despite improvements in anesthesia, surgical technique, and medical therapy. The pathogenesis of postoperative atrial fibrillation is considered to be multifactorial. However oxidative stress is a major contributory factor representing the unavoidable consequences of ischemia/reperfusion cycle occurring in this setting. Considerable evidence suggests the involvement of reactive oxygen species (ROS) in the pathogenic mechanism of this arrhythmia. Interestingly, the deleterious consequences of high ROS exposure, such as inflammation, cell death (apoptosis/necrosis) or fibrosis, may be abrogated by a myocardial preconditioning process caused by previous exposure to moderate ROS concentration known to trigger survival response mechanisms. The latter condition may be created by n-3 PUFA supplementation that could give rise to an adaptive response characterized by increased expression of myocardial antioxidant enzymes and/or anti-apoptotic pathways. In addition, a further reinforcement of myocardial antioxidant defenses could be obtained through vitamins C and E supplementation, an intervention also known to diminish enzymatic ROS production. Based on this paradigm, this review presents clinical and experimental evidence supporting the pathophysiological and molecular basis for a novel therapeutic approach aimed to diminish the incidence of postoperative atrial fibrillation through a non-hypoxic preconditioning plus a reinforcement of the antioxidant defense system in the myocardial tissue.

Resultados clínicos de la resincronización ventricular en pacientes con insuficiencia cardíaca severa

: Fourteen patients (11 male), whose mean age was 68years, with a severe and refractory cardiac failure, have been treated in our unit using intraventricu-lar resynchronization with pacemakers. Eight had a coronary heart disease and six a dilated myocar-diopathy. The pacemaker was implanted transvenously, with conventional stimulation in atrium andright ventricle. The left ventricle was stimulated through an epicardial vein, accessed through the coro-nary sinus.

Hospitalizaciones asociadas al diagnóstico de fibrilación auricular en Chile: Tendencia creciente en la última década

Los egresos hospitalarios con el diag-nostico de FA fueron obtenidos del Ministerio de Salud (codigo I-48 FA) de la Clasificacion Internacional de Enfermedades. Hubo datos disponibles solo para los anos 2002 al 2007; se analizo genero, grupos etarios y regiones del pais. Las tasas (T) de egresos hospitalarios con este diagnostico por 10.000 habitantes (H) fueron calculadas en base a la poblacion proyectada del ultimo censo nacional para los anos senalados. Para el analisis estadistico se utilizo el test de proporsiones de Z.

Taquicardia de complejo ancho en paciente con fibrilación auricular permanente

Un hombre de 80 años con historia de diabetes mellitus e infarto antiguo del miocardio es ingresado con insuficiencia cardíaca y neumopatía aguda. Presentaba Fibrilación auricular y no recibía antiarrítmicos. Despues de administración de broncodilatadores desarrolló una taquicardia a complejo ancho. Se presentan los trazados electrocardiográficos y se discute el mecanismo de la arritmia René Asenjo

VALIDACIÓN DEL TEST DE TROPONINAS EN PLASMA A PARTIR DE UNA POBLACIÓN SANA. UNA EXPERIENCIA LOCAL

Las troponinas corresponden a pro-teinas estructurales del miocardiocito, su presencia en plasma se utiliza como marcador de injuria miocardica. El test troponinas en plasma se utiliza actualmente para detectar dano miocardico en pacientes en quienes se sos -pecha un infarto agudo al miocardio; para este proposito se toma como referencia valores de referencia validados en poblaciones de Inglaterra o Estados Unidos.

Nueva estrategia de preacondicionamiento no hipóxico que atenúa el efecto de la Isquemia-Reperfusión en pacientes sometidos a cirugía cardíaca con circulación extracorpórea

Antecedentes de la investigacion: El preacondicionamiento hipoxico se ha utilizado como medida de proteccion para el miocardio, sin embargo es clinicamente inaplicable. Las especies reactivas de oxigeno (ERO), estarian involucradas en la produccion de modificaciones estructurales y electricas, que hacen susceptible al tejido auricular a arritmias y disfuncion contractil. Por lo tanto, un reforzamiento del sistema de defensa antioxidante protegeria al corazon del dano hipoxico. Objetivo: Determinar el efecto de la suplementacion de Omega 3 y vitaminas antioxidantes C y E, en el estado antioxidante de pacientes sometidos a cirugia cardiaca con circulacion extracorporea (CEC). Metodos: Un total de 50 pacientes se incluyo en el protocolo. Se randomizaron 15 pacientes a recibir Omega 3, siete dias antes de la cirugia, y vitaminas C y E, dos dias antes de la cirugia, ambos hasta el post-operatorio y 15 a placebo. Los valores controles se obtuvieron en 20 pacientes sin intervencion farmacologica preacondicionante. Se obtuvieron muestras de sangre en condiciones basales, antes del inicio de las vitaminas, 6-8 h post-operatorio y al alta para la determinacion del estado antioxidante (capacidad antioxidante del plasma, FRAP; relacion glutation reducido (GSH)Zoxidado (GSSG) y enzimas antioxidantes en eritrocito y dano oxidativo (malondialdehido y F2 - isoprostanos en plasma). En tejido se midio por Western Blot la expresion de la subunidad catalitica de la NADPH oxidasa (NOX-2) y la citosolica p47phox. La localizacion de la subunidad de membrana NOX-2/gp91phox se evidencio mediante inmunofluorescencia. Como indice de dano oxidativo en tejido se utilizaron los niveles de malondialdehido. Se utilizo analisis multivariado ANOVA con post-test de una via de Bonferroni. Resultados: Al momento de la cirugia, los pacientes que habian recibido tratamiento, presentaban niveles de GSH/GSSG un 56% mayor (p<0.03); en el postoperatorio inmediato tenian valores mayores de FRAP (30%; p<0.04) y glutation peroxidasa (25%; p<0.05) que el grupo placebo. En el tejido auricular habia menor expresion de la subunidad NOX-2/gp91 phox y de la subunidad citosolica p47phox en los tratados. La presencia de gp91phox en la membrana plasmatica de los cardiomiocitos se confirmo por inmunofluorescencia. En cuanto al dano oxidativo en plasma y tejido, los niveles de malondialdehido fueron 21 (p<0.03) y 46 % (p<0.05) menores y los niveles plasmaticos de F2-isoprostano 27% (p<0.04) menores en el grupo que recibio tratamiento. Conclusiones: La suplementacion con Omega 3 y vitaminas antioxidantes, atenua el dano oxidativo en pacientes sometidos a cirugia cardiaca con CEC. Se sugiere que este efecto podria obedecer al menos en parte a una regulacion negativa de la actividad de la NADPH oxidasa de los cardiomiocitos.