Ernesto Larraín

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.

Puente al trasplante de 4 semanas utilizando el sistema de asistencia ventricular LEVITRONIX CENTRIMAG® en el shock cardiogénico post-infarto al miocardio. Caso clínico.

Introduction. Myocardial infarction cardiogenic shock portends a high mortality even if early revascularization is achieved. Biventricular assist devices have not been used in Chile in this critical setting. Methods/Results. We report a case of a 55 year-old diabetic man who suffered an acute chest pain and ventricular fibrillation. Prompt out-side hospital cardioversion/reanimation restored pulse and allowed emergency room transfer on mechanical ventilation. Electrocardiogram showed an anterior myocardial infarction and early revascularization was achieved by anterior descending artery angioplasty. However, severe cardiogenic shock continued in spite of inotropic and intraortic balloon pump support. LEVITRONIX CENTRIMAG® biventricular mechanical circulatory support was inserted during reanimation for recurrent ventricular fibrillation and the patient listed for urgent cardiac transplantation upon stabilization. Heart transplantation was performed successfully 28 days later and the patient dismissed after a 21-day recovery period. Six months after transplant patient is in NYHA functional class I with normal biventricular function. Conclusion. LEVITRONIX CENTRIMAG® biventricular mechanical circulatory support could be used successfully as a bridge-to-transplant for myocardial infarction cardiogenic shock. This is the longest biventricular circulatory support reported in Chile .

Experiencia clínica con 53 trasplantes cardiacos consecutivos

Introduction. Heart transplantation is the therapy of choice for advance heart failure. Our group developed two transplant programs at Instituto Nacional del Torax and Clinica Davila. We report our clinical experience based on distinctive clinical policies. Patients and Methods. Fifty-three consecutive patients were transplanted between November 2008 and April 2013, representing 51% of all Chilean cases. Distinctive clinical policies include intensive donor management, generic immunosuppression and VAD (ventricular assist devices) insertion. Results. Ischemic or dilated cardiomyopathy were the main indications (23(43%) each), age 48+13 years and 48(91%) were male. Transplant listing Status: IA 14(26%)(VAD or 2 inotropes), IB 14(26%)(1 inotrope) and II 25(47%)(no inotrope). Mean waiting time 70+83 days. Twelve (24%) were transplanted during VAD support (median support: 36 days). Operative technique: orthotopic bicaval transplant with ischemia time: 175+54 min. Operative mortality: 3 (6%), all due to right ventricular failure. Re-exploration for bleeding 2 (4%), stroke 3(6%), mediastinitis 0(0%), pneumonia 4(8%), and transient dialysis 6 (11%). Mean follow-up was 21+14 months. Three-year survival was 86+6%. One patient died of Pneumocystis jirovecii pneumonia and the other died suddenly (non-compliance). Freedom from rejection requiring specific therapy was 80+7% at 3 years of follow-up. Four hundred eighty four endomyocardial biopsies were done: 11(2.3%) had 2R rejection. All survivors are in NYHA (New York Heart Association) functional class I and all but one have normal biventricular function. Conclusion. Mid-term results are similar to those reported by the registry of the International Society for Heart and Lung Transplantation. This experience has a higher proportion of VAD support than previous national series. Rejection rates are low in spite of generic immunosuppression.

Fibroelastoma of the mitral valve--a curable cause of stroke.

THE LANCET Neurology Vol 1 October 2002 http://neurology.thelancet.com 388 A 39-year-old healthy male chemical engineer, with no significant previous medical history, presented at our hospital with sudden onset (over a period of 4 h) of dysphasia, agraphia, mild right hand hemiparesis, and asterognosis. On admission, we did a neurological examination which showed mild attention impairment, anterograde amnesia, mild conduction aphasia, and impairment of right-left discrimination. Somatic motor examination revealed a right pyramidal syndrome with brachial hemiparesis and extensor plantar reflex on the right. Superficial sensation was normal, but position sense of the right upper limb was impaired. A general medical examination showed mildly elevated blood pressure but was otherwise unremarkable. He was not receiving medical treatment and was a moderate cigarette smoker (4–6 cigarettes a day). A brain computed tomography scan done 12 h after the onset of clinical symptoms was normal, but diffusion weighted brain magnetic resonance imaging showed a small area of high intensity signal on the left temporal cortex, also recognisable on FLAIR sequences, but not on T1 or T2 weighted images (figure 1). Transthoracic (TTE) and transoesophageal (TEE) echocardiographic evaluation detected a 0·8 10 mm diameter round mass on the left Case report

Influencia del sistema nitridérgico en la respuesta contráctil a fenilefrina de anillos de vasos usados en revascularización coronaria

Vessel rings of 7 to 10 mm length were obtained from32 patients subjected to coronary vascular surgery. Fourteen samples of radial artery, 12 samplesof internal mammary artery and 15 samples of saphenous vein were obtained. A maximalcontraction was induced with KCl and dose response curves for phenylephrine (FE) in the absenceor presence of L-arginine and L-arginine methyl ester (L-NAME), were constructed.

Bridge to transplant or recovery in cardiogenic shock in a developing country

Background Durable mechanical support devices are prohibitively expensive in our health system and may be unsuitable for critically ill patients. CentriMag is an alternative bridge to transplantation or recovery. Methods We retrospectively reviewed 28 patients (23 males) aged 13–60 years who received CentriMag support. The etiology was ischemic in 13 (46%), dilated cardiomyopathy in 8 (29%), and others in 7 (25%). All patients were in Interagency Registry for Mechanically Assisted Circulatory Support class I, and 27 (96%) had multiorgan failure; 2 (7%) were post-cardiotomy and 12 (43%) had a previous cardiac arrest (mean arrest time 21 ± 17 min). Results Thirty-day post-implant survival was 79% (22 patients). Twenty (71%) patients were successfully bridged to transplantation or recovery. The mean support time was 40 days; 12 (43%) patients had >4-weeks’ support (longest was 292 days). Eight (29%) patients died on support. Complications included bleeding in 10 (36%) cases, immediate stroke in 4 (14%), and dialysis in 8 (29%). There was no stroke during subsequent support. Eighteen (64%) patients underwent transplantation, and 17 of them were discharged. Two (7%) patients recovered and were discharged. Two-year survival was 62% ± 10%. Mean follow-up was 21 months (total follow-up 579 months). Two (7%) patients died during follow-up. All survivors were in New York Heart Association class I. Conclusions CentriMag is useful for medium-term support for cardiogenic shock in a developing country. Support for >4 weeks is feasible. The stroke rate is low during support. The major drawback is prolonged intensive care unit stay.

Reporte de dos casos clínicos de melanoma con metástasis cardíacas: ("Dos caras de una misma moneda")

A 39 year old man presented with signs of an ischemic in-farct in the territory of the medial cerebral artery. A large mobile mass was present in the left atrium and a biopsy showed tissue heavily infiltrated with fat and resection was not possible. A small lesion located at the dorsum allowed a histologic confirmation of a melanoma. The patient died 4 months after surgery. The second patient, a 34 year old woman being treated with chemotherapy for an ovarian melanoma was found to have a right atrial mass. After successful resection of the mass a metastasis of the original melanoma was confirmed and the patient remains in good condition at mid term follow up.

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.