Diagnóstico diferencial de las taquicardias de complejo ancho: un desafío permanente / Wide QRS tachycardia: a diagnostic challenge

El diagnóstico electrocardiográfico correcto de la causa de una taquicardia de complejo QRS ancho (TCA) es fundamental, ya que tanto el manejo, como el pronóstico del paciente, es diferente según su etiología, y define el estudio que debemos realizar. Numerosos criterios y algoritmos han sido descritos para diferenciar el origen de estas taquicardias. Sin embargo, muchos de estos son complejos y difíciles de aplicar para el médico menos experimentado. Esto es particularmente importante en los servicios de emergencia, donde se necesita una definición rápida que permita un manejo agudo apropiado. En la presente revisión analizamos los diferentes mecanismos de las TCA y los principales criterios diagnósticos en el ECG, reforzando, especialmente, aquellos de aplicación rápida y de alto rendimiento diagnóstico.

The correct electrocardiographic diagnosis of the cause of a wide QRS complex tachycardia (WCT) is essential since both management and prognosis of the patient. The correct electrocardiographic diagnosis of the cause of a wide QRS complex tachycardia (WCT) is essential since both management and prognosis is different according to its etiology and defines the study that we should perform. Numerous criteria and algorithms have been described to differentiate the origin of these tachycardias. However, many of these are complex and difficult to apply to the less experienced doctor. This is particularly important in emergency rooms, where a rapid definition is needed to allow proper therapy. In this review we analyze the different mechanisms of WCT and the main EKG diagnostic criteria, emphasizing those which can be applied rapidly and have high diagnostic value.

Efecto de la terapia de resincronización ventricular en los parámetros de disfunción endotelial y función sistólica izquierda en pacientes con insuficiencia cardíaca crónica y bloqueo completo de rama izquierda / Endothelial dysfunction, left ventricular function, and chronic heart failure with complete left bundle branch block: effect of resynchronization therapy

Resumen: Introducción: La insuficiencia cardíaca crónica (ICC) es una condición compleja asociada a inflamación sistémica y a disfunción endotelial (DE) cuya patogénesis no es bien comprendida. Objetivo: Evaluar una posible relación entre marcadores de DE periférica con la respuesta a terapia de resincronización ventricular (TRV). Método: 20 pacientes con ICC, QRS ≥120ms y fracción de eyección ventricular izquierda (FEVI) ≤35% se estudiaron pre y 6 meses post-TRV con: Minnesota Living with Heart Failure Questionnaire (MLHFQ); test de marcha (TM-6min); Ecocardiografía-2D y SPECT de perfusión gatillado en reposo; proteína C-reactiva ultra sensible (us-PCR); péptido natriurético cerebral (pro-BNP); células endoteliales circulantes (CEC); moléculas de adhesión soluble vascular (sVCAM) e intercelular (sICAM); interleukina-6 (IL-6) y Factor von Willebrand (FvW). Se clasificaron como respondedores o no a TRV según criterios preestablecidos. Resultados: Promedios basales: pro-BNP 5.290pg/ml; us-PCR 1,7ug/mL; MLHFQ 72; TM-6min 391 metros. Las CEC y sICAM estaban sobre límites normales. Post-TRV, el 50% fue respondedor: 11/20 mejoraron ≥1 clase NYHA y ≥10% del TM-6min; ML-HFQ disminuyó (p<0.0001); FEVI mejoró (p=0.003); volumen final sistólico disminuyó (p=0.008) y también pro-BNP (p=0.03). En los respondedores, las CEC disminuyeron, persistiendo elevadas, sobre lo normal. Existieron correlaciones entre cambios de pro-BNP con TM-6min y entre us-PCR con MLHFQ y FvW (p≤0.004 en todas). Conclusiones: En ICC existe evidencia de significativa DE, expresada por sICAM y CEC, biomarcador periférico sensible. Estas disminuyeron 6 meses post-TRV, persistiendo sobre el límite normal. Otros parámetros funcionales e inflamatorios se correlacionaron en el grupo total, sin diferencias entre grupos respondedores y no respondedores.

Abstract: Introduction: Chronic heart failure (CHF) is a complex condition associated with systemic inflammation and endothelial dysfunction (ED) whose pathogenesis is not well understood. Objective: to evaluate a possible relationship between peripheral ED markers and response to cardiac resynchronization therapy (CRT). Method: 20 patients with CHF, QRS ≥120ms and left ventricular ejection fraction (LVEF) ≤35% were studied before and 6 months post-CRT. Minnesota Living with Heart Failure Questionnaire (MLHFQ); walking test (6min-WT); 2D-echocardiography and gated perfusion SPECT at rest; ultra-sensitive C-reactive protein (us-CRP); brain natriuretic peptide (pro-BNP); circulating endothelial cells (CEC); vascular soluble adhesion (sVCAM) and intercellular adhesion molecules (sICAM); interleukin-6 (IL-6) and von Willebrand Factor (vWF) were measured in all subjects. They were classified as responders or not to CRT, according to pre-established criteria. Results: Basal means: pro-BNP 5,290 pg / ml; us-CRP 1.7 ug/mL; MLHFQ 72; 6min-WT 391 meters. The CEC and IL-6 were above normal limits. Post-CRT, 50% were responders: 11/20 improved ≥1 NYHA class and ≥10% increase in 6min-WT; MLHFQ decreased (p <0.0001); LVEF improved (p = 0.003); final systolic volume decreased (p = 0.008) and also pro-BNP (p= 0.03). In responders CEC decreased, persisting over normal limits. There were correlations between changes of pro-BNP with TM-6min and between us-PCR with MLHFQ and vWF (p≤0.004 in all). Conclusions: In CHF there is evidence of significant ED, expressed by sICAM and CEC, a sensitive peripheral biomarker that decreased 6 months post-CRT although persisting above normal limits. Other functional and inflammatory parameters were correlated in the total group, without differences between responders and non-responders.

Taquicardia de complejo ancho en paciente con fibrilación auricular permanente / Wide QRS tachycardia in a patient with persistent atrial fibrillation

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.

An 80 year old man, with a history of diabetes mellitus and remote myocardial infarction is admitted with heart failure and pneumonia He was in atrial fibrillation and was not on anti arrhythmic drugs. After receiving broncodilators he developed a wide QRS tachycardia. ECG tracings are presented and the mechanism of this tachycardia is discussed.

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).

Validación del test de troponinas en plasma a partir de una población sana: una experiencia local / Validation of normal values for troponin i plasma levels in a chilean population

Introducción: Las troponinas corresponden a proteínas estructurales del miocardiocito, su presencia en plasma se utiliza como marcador de injuria miocárdica. El test troponinas en plasma se utiliza actualmente para detectar daño miocárdico en pacientes en quienes se sospecha un infarto agudo al miocardio; para este propósito se toma como referencia valores de referencia validados en poblaciones de Inglaterra o Estados Unidos. Objetivo: El propósito de este estudio obtener valores de referencia para nuestra población local. Métodos y resultados: Se efectuó una determinación de troponina I en 500 sujetos sanos, se obtuvo el valor promedio de troponina I para esta población y el valor percentil 99 para esta población que se considera internacionalmente como el valor de referencia para determinar el límite normal, el valor P99 resultó significativamente menor en mujeres respecto a hombres. Conclusión: En conclusión, se han obtenido valores de referencia para aplicar el test de troponina I en nuestro medio local.

Background: Troponins are myocardiocyte proteins; their plasma level is used as a marker for myocardial injury. In the diagnosis of myocardial infarction values currently used as cut points are those validated elsewhere (USA, UK). Aim: In this study we aimed to determine normal limits of Troponin I in a sample of Chilean subjects. Methods and results: 500 healthy subjects had their troponin I levels measured, computing the mean and 99 percentile (p99) values. Both parameters were significantly lower in females compared to males (mean ± SD 0.089 +/- 0.047 vs 0.102 +/- 0.063, p<0.01; p99 0.02 vs 0.03, respectively). Conclusion: These troponin I values may be used to assess the likelihood of myocardial infarction in Chilean subjects.

[Tachycardiomyopathy as a reversible cause of heart failure: report of one case]. / Taquicardiomiopatía, causa reversible de insuficiencia cardiaca: caso clínico.

Tachycardiomyopathy is a potentially reversible cause of heart failure. It can be induced by supraventricular or ventricular arrhythmias. When these are treated, systolic function improves or normalizes. We report a 20 year-old male with deterioration of left ventricular function and dilated cardiomyopathy secondary to an incessant atrial tachycardia that was treated with radiofrequency catheter ablation. After the procedure, the patient experienced a significant improvement of his ventricular function.

Taquicardiomiopatía, causa reversible de insuficiencia cardiaca: caso clínico / Tachycardiomyopathy as a reversible cause of heart failure: Report of one case

Tachycardiomyopathy is a potentially reversible cause of heart failure. It can be induced by supraventricular or ventricular arrhythmias. When these are treated, systolic function improves or normalizes. We report a 20year-old male with deterioration of left ventricular function and dilated cardiomyopathy secondary to an incessant atrial tachycardia that was treated with radiofrequency catheter ablation. After the procedure, the patient experienced a significant improvement of his ventricular function.

Hospitalizaciones asociadas al diagnóstico de fibrilación auricular en Chile: tendencia creciente en la última década / Hospitalization for atrial fibrillation in Chile: a growing tendency in the last decade

Antecedentes: Publicaciones internacionales señalan que las hospitalizaciones por fibrilación auricular (FA) están aumentando, lo que tiene importantes implicaciones para la salud pública y el cardiólogo. En Chile no se dispone de mayor información sobre el problema. Objetivo: Estudiar las hospitalizaciones asociadas al diagnóstico de FA en Chile. Métodos: Los egresos hospitalarios con el diagnóstico de FA fueron obtenidos del Ministerio de Salud (código 1 48 FA) de la Clasificación Internacional de Enfermedades. Hubo datos disponibles solo para los años 2002 al 2007; se analizó género, grupos etarios y regiones del país. Las tasas (T) de egresos hospitalarios con este diagnóstico por 10.000 habitantes (H) fueron calculadas en base a la población proyectada del último censo nacional para los años señalados. Para el análisis estadístico se utilizó el test de proporsiones de Z. Resultados: La T total de egreso hospitalario asociada al diagnóstico de FA el año 2002 fue de 2,2/10.000 H la que aumentó gradualmente hasta una T de 2,8/10.000 H el año 2007 (P<0,001). Las T de hombres y mujeres el año 2002 fueron de 2,2 y 2,1 y aumentaron hasta 2,8 y 2,7/10.000 H el 2007, respectivamente (P<0,001). En el grupo etario <40 años no se observaron mayores variaciones de las T entre los años 2002 y 2007 (P<0,01). En los mismos períodos las T en pacientes de 40-64 años fueron de 2,9 y 3,6/10.000 H, entre 65-79 años 14,2 y 18,5/10.000 H (P<0,001), mientras que en >80 años las T fueron de 32,4 y 43,7/10.000 H respectivamente (P<0,0001). En las regiones I-II-III, las T no presentaron variaciones, pero en las regiones X-XII-XII las T aumentaron gradualmente en el periodo estudiado (2,3 y 3,5 /10.000 H los años 2002 y 2007, respectivamente). Conclusiones: Este trabajo muestra que en nuestro país, las H por FA muestran una tendencia creciente, con un incremento de 27 percent en el periodo estudiado, especialmente en > 65 años, y en las regiones del sur del país...

Background: Hospitalization for atrial fibrillation (AF) is reported to be increasing worldwide, becoming a cardiovascular health problem. Scarce data on this subject is available in Chile. Aim: To describe hospitalizations related to AF in Chile. Method: The discharge diagnosis of AF (ICD I48)was obtained form the Ministry of Health reports. Only data from 2002 through 2007 was available. Gender, age and location (regions) were analyzed. A projection derived form the last population census was used to estimate rates per 10.000 people discharged with a diagnosis of AF Results: The rate of discharges with a diagnosis of AF increased from 2.2 per 10.000 in 2002 to 2.8 per 10.000 in 2007. Male and female rates were 2.2 and 2.1 respectively in 2002, increasing to 2.8 and 2.7 in 2007. The rate of AF discharge remained approximately constant for those under 40 years of age. In contrast, the corresponding rates for 2002 and 2007 increased from 2.9 to 3.6 for those aged 40-64, 14.2 to 18.5 for those aged 65-79 and 32.4 to 43.7 for those over 80. AF discharge rates did no vary in Regions I to III while they increased from 2.3 to 3.5 in regions X to XII. Conclusion: The rate of discharge with a diagnosis of AF has increased in Chile approximately 25 percentfrom 2002 to 2007. This phenomenon is more marked in those over 65 years of age and those living in the southern regions of the country.

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.

Prevención primaria y secundaria de muerte súibita en el ICD Registry Latin America / Primary and secondary prevention of sudden cardiac death in the icd registry-latin america

INTRODUCTION AND OBJECTIVES: The ICD Registry is an observational study conducted in Latin America to collect data on indications and follow-up care for primary or secondary prevention of sudden cardiac death patients. The objective of this study is to compare and evaluate the characteristics of primary versus secondary prevention in the patient population enrolled in the registry. METHODS: Demographic data, indication, etiology, NYHA functional class and left ventricular ejection fraction (LVEF), pharmacological treatment at implant and the type of ICD implanted were also collected. During the follow-up period the ICD therapies delivered, patient hospitalizations and mortality were evaluated. RESULTS: 507 patients were evaluated. Average age 60 +/- 14 years old, 78% male. Coronary heart disease was the most common etiology (43.6%). NYHA Functional Class I/II at the time of implant (73.6%). Average LVEF was 34 +/- 16%. Out of 507 patients, 189 received an ICD for primary prevention; 318 for secondary prevention. Primary prevention patients were older, predominantly male and had a lower EF. The rate of mortality and hospitalizations were similar between both groups with a higher rate of appropriate therapies in secondary prevention patients. CONCLUSIONS: This is the first study to demonstrate clinical characteristics of primary prevention patients in Latin America. There were no significant statistically differences in a short follow-up period in mortality or hospitalization as compared to the secondary prevention patient population in the Registry.

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.

[Primary and secondary prevention of sudden cardiac death in the ICD Registry-Latin America]. / Prevención primaria y secundaria de muerte súibita en el ICD Registry Latin America.

INTRODUCTION AND OBJECTIVES: The ICD Registry is an observational study conducted in Latin America to collect data on indications and follow-up care for primary or secondary prevention of sudden cardiac death patients. The objective of this study is to compare and evaluate the characteristics of primary versus secondary prevention in the patient population enrolled in the registry. METHODS: Demographic data, indication, etiology, NYHA functional class and left ventricular ejection fraction (LVEF), pharmacological treatment at implant and the type of ICD implanted were also collected. During the follow-up period the ICD therapies delivered, patient hospitalizations and mortality were evaluated. RESULTS: 507 patients were evaluated. Average age 60 +/- 14 years old, 78% male. Coronary heart disease was the most common etiology (43.6%). NYHA Functional Class I/II at the time of implant (73.6%). Average LVEF was 34 +/- 16%. Out of 507 patients, 189 received an ICD for primary prevention; 318 for secondary prevention. Primary prevention patients were older, predominantly male and had a lower EF. The rate of mortality and hospitalizations were similar between both groups with a higher rate of appropriate therapies in secondary prevention patients. CONCLUSIONS: This is the first study to demonstrate clinical characteristics of primary prevention patients in Latin America. There were no significant statistically differences in a short follow-up period in mortality or hospitalization as compared to the secondary prevention patient population in the Registry.

Amiodarona en alta dosis de carga oral única: parámetros farmacocinéticos en pacientes sometidos a cirugía coronaria / High loading dose of amiodarone: pharmacokinetics in patients undergoing coronary

Antecedentes: Amiodarona (A) es la droga antiarrítmica más utilizada en la actualidad. No obstante, algunos aspectos de su compleja farmacología son todavía poco conocidos en ciertos grupos de pacientes. Objetivo: Estudiar los parámetros farmacocinéticos de A después de una alta dosis de carga oral en pacientes (P) sometidos a cirugía coronaria. Métodos: Cuarenta y tres P sometidos a cirugía coronaria recibieron una dosis oral de 30 mg/kg en dosis fraccionada como tratamiento profiláctico de arritmias en el post operatorio. Las concentraciones sanguíneas de la droga fueron medidas a tiempos sucesivos, por HPLC, hasta las 96 h de su administración. En base a la curva obtenida de concentración sanguínea vs tiempo, los parámetros farmacocinéticos fueron calculados mediante un programa computacional independiente del modelo compartimental. Resultados: La concentración sanguínea de A alcanzó un valor máximo de 2,3 +/- 1,5µg/ml a las 10 h de la administración de la droga. Posteriormente, se observó un descenso gradual con un valor de 0,4 +/- 0,1 µg/ml a las 96h de administración. Los parámetros farmacocinéticos obtenidos fueron: Vida media 29,1 +/- 11,3h; Area bajo la curva 0’96 63,6 +/- 22,3 (µg/ml)h; Clearance total 6,1 +/- 2,2 ml/min/kg; Volumen de distribución 15,6 +/- 5,4 L/kg. Conclusiones: La farmacocinética de A presenta diferencias con lo encontrado en estudios de dosis única en otros grupos de pacientes. El presente trabajo puede servir para esquemas de dosificación menos empíricos de A.

Background: Amiodarone is currently the most commonly used antiarrhythmic drug. However, some aspects of its complex pharmacokinetics in particular groups of patients are not well known. Aim: to study the pharmacokinetics of amiodarone after a high loading oral dose in patients undergoing coronary revascularization surgery. Methods: Forty three patients operated on for coronary artery disease received oral dose amiodarone, 30mg/Kg, in a fractioned dose as a prophylactic antiarrhythmic medication following surgery. Blood amiodarone concentration was measured at successive intervals for 96 hr. A software based on a non compartmental model was used to determine pharmacokinetic parameters. Results: Maximal blood concentration of amiodarone was 2.3 +/-1.5µg/ml 10hr after drug administration. A subsequent gradual decrease of amiodarone blood level was observed, down to 0.4 +/- 0.1µg/ml at 96hr post drug administration. The half-life time was 29.1 +/- 11.3hr. The area under de 0 to 96hr curve was 63.6 +/- 22.3µg/ml.Total clearance was 6.1 +/- 2.2 ml/min/kg. The distribution volume was 15.6 +/- 5,4 L/kg. Conclusion: Pharmacokinetics of amiodarone differs from that obtained following a single dose in other groups of patients. The data provided may be used to determine more objective amiodarone dosing schemes.

Non-hypoxic preconditioning of myocardium against postoperative atrial fibrillation: mechanism based on enhancement of the antioxidant defense system.

Oxidative stress underlies postoperative atrial fibrillation and electrophysiological remodelling associated with rapid atrial pacing. An increasing body of evidence indicates that the formation of reactive oxygen species (ROS) released following extracorporeal circulation are involved in the structural and functional myocardial impairment derived from the ischemia-reperfusion cycle. ROS behave as intracellular messengers mediating pathological processes, such as inflammation, apoptosis and necrosis, thereby participating in the pathophysiology of atrial fibrillation. Thus, increased superoxide (O(2)(.-)) production has been found in isolated atrial cardiomyocytes from patients with atrial fibrillation. Therefore, it seems reasonable to assume that the reinforcement of the antioxidant defense system should protect the heart against functional alterations in the cardiac rhythm. On this line, antioxidant enzyme induction through in vivo exposure to moderate concentration of ROS is associated with a reduction in the susceptibility of myocytes to ROS-induced injury. This response could be due to a prevailing effect of survival over apoptotic pathway. Previously, tissue preconditioning caused by prior exposure to an ischemia/reperfusion cycle has been successfully applied in experimental models and clinical settings associated with oxidative damage by ROS. However, such hypoxic preconditioning method is harmful to be applied to many clinical conditions associated with oxidative stress. In turn, experimental studies have revealed that non-enzymatic antioxidants produce a significant functional amelioration in cardiomyocytes subjected to an oxidative challenge. Moreover, clinical studies with patients scheduled for primary coronary artery bypass graft surgery had a reduced incidence of postoperative atrial fibrillation. We present the hypothesis of non-hypoxic preconditioning based on the association of pretreatment with n-3 polyunsaturated fatty acids followed by ascorbate plus alpha-tocoferol supplementation diminishes the incidence of postoperative atrial fibrillation in patients subjected to cardiac surgery with extracorporeal circulation.