Shifting to a control diet after a high-fat, high-sucrose diet intake induces epigenetic changes in retroperitoneal adipocytes of Wistar rats

The aim of the study was to analyze the phenotypic and epigenetic changes induced by the shift to a chow diet after an obesogenic environment. Animals were randomized to fed chow (control group) or high-fat–sucrose diet (HFS). After 10 weeks, half of the rats fed with HFS diet were reassigned to a chow diet (rest group) while the other half continued with the obesogenic diet (HFS group) until week 20. Changes in fat content, biochemical profile, and DNA methylation levels of several gene promoters from retroperitoneal adipocytes were analyzed. HFS diet intake for 10 weeks induced obese phenotype in the animals, increasing body weight and fat content. These effects were maintained until the end of the trial in HFS group, where an increase in liver fat content, a modification of lipid profile, and retroperitoneal adipose tissue hypertrophy were also observed. Changing the dietary pattern reversed these parameters. Epigenetic analysis showed that HFS diet intake for 20 weeks hypermethylated several CpG sites (6.7 and 29.30) and hypomethylated CpG site 15 from leptin gene promoter. Moreover, the obesogenic diet also hypomethylated CpG site 1 from Fasn (fatty acid synthase) gene promoter, without changes on Ppargc1a (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), Srebf1 (sterol regulatory element-binding transcription factor 1), and aquaporin 7. Shifting to a chow diet reverted HFS-induced DNA methylation levels of some CpG sites of leptin promoter. Changing the dietary pattern hypomethylated a CpG site of Srebf1 and hypermethylated other CpGs on Ppargc1a and Fasn promoter. This study shed light on the reversibility of phenotypical and epigenetic changes induced by a HFS diet intake (AU)

Shifting to a control diet after a high-fat, high-sucrose diet intake induces epigenetic changes in retroperitoneal adipocytes of Wistar rats.

The aim of the study was to analyze the phenotypic and epigenetic changes induced by the shift to a chow diet after an obesogenic environment. Animals were randomized to fed chow (control group) or high-fat-sucrose diet (HFS). After 10 weeks, half of the rats fed with HFS diet were reassigned to a chow diet (rest group) while the other half continued with the obesogenic diet (HFS group) until week 20. Changes in fat content, biochemical profile, and DNA methylation levels of several gene promoters from retroperitoneal adipocytes were analyzed. HFS diet intake for 10 weeks induced obese phenotype in the animals, increasing body weight and fat content. These effects were maintained until the end of the trial in HFS group, where an increase in liver fat content, a modification of lipid profile, and retroperitoneal adipose tissue hypertrophy were also observed. Changing the dietary pattern reversed these parameters. Epigenetic analysis showed that HFS diet intake for 20 weeks hypermethylated several CpG sites (6.7 and 29.30) and hypomethylated CpG site 15 from leptin gene promoter. Moreover, the obesogenic diet also hypomethylated CpG site 1 from Fasn (fatty acid synthase) gene promoter, without changes on Ppargc1a (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), Srebf1 (sterol regulatory element-binding transcription factor 1), and aquaporin 7. Shifting to a chow diet reverted HFS-induced DNA methylation levels of some CpG sites of leptin promoter. Changing the dietary pattern hypomethylated a CpG site of Srebf1 and hypermethylated other CpGs on Ppargc1a and Fasn promoter. This study shed light on the reversibility of phenotypical and epigenetic changes induced by a HFS diet intake.

Ventrículo derecho: relación con patología respiratoria y patología del ventrículo izquierdo / Right ventricle: relationship with pulmonary and left ventricular pathology

In a previous article, we reviewed path physiological concepts of right ventricle considering its importance in cardio respiratory diseases and its behavior was compared with left ventricle. Measurement of right ventricular function is complex due to its pre load dependence. Remarkable progress has been developed in methods to measure anatomy and function. Probably a functional definition might include diverse parameters as geometry, hypertrophy, dilatation, contraction, oxygen supply to muscular wall and ejected volume. In the present review, we describe the behavior of right ventricle in different pathologies. In first place, we analyze its behavior in respiratory diseases and afterwards in diseases, which involves pulmonary circulation and left ventricular failure. Our purpose is to stimulate pulmonary physicians and cardiologists in the study of this common entity. A complete description of the diseases, which causes right ventricular failure, goes beyond the limits of this article.

En una publicación previa actualizamos los conceptos fisiopatológicos, que rigen la función del ventrículo derecho (VD), considerando su importancia en enfermedades cardiorespiratorias, y describimos su comportamiento al compararlo con el ventrículo izquierdo (VI). La función del VD es difícil de medir por su alta dependencia de la precarga, sin embargo, ha habido progresos en los métodos para determinar su anatomía y su función. Es probable que la definición de función deba incluir parámetros diversos, como geometría, hipertrofia, dilatación, contracción, aporte de oxígeno a la pared y volumen eyectado. En la presente revisión describiremos el comportamiento del VD frente a diversas patologías. En primer lugar analizaremos su comportamiento frente a patologías respiratorias y luego frente a patologías que comprometen la circulación pulmonar y la Insuficiencia cardíaca congestiva (ICC). Nuestro propósito es estimular a la comunidad médica de Enfermedades Respiratorias y Cardiología a profundizar en esta entidad común. La descripción completa de cada uno de los cuadros que causan falla cardíaca derecha, sobrepasa los límites de este artículo.

Fisiopatología del ventrículo derecho / Right ventricle pathophysiology

Right ventricle has traditionally been underemphasized considering the amount of information and investigation about the left ventricle, its pathologies and treatments. Old physiological concepts considered right ventricle as a secondary organ without significance in cardiovascular pathology. The scope of respiratory diseases usually deals with heart involvement or cor pulmonale secondary to pulmonary diseases. Nevertheless, the limited availability of cardiac techniques to evaluate right ventricle has restricted the information about its physiological behavior and diseases. In the last five years, a renewed interest in right ventricle provided significative changes in concepts, methods of evaluation and treatment. In this article, we will review recent physiological concepts about right ventricle, based in up-to-date publications on the mechanisms and pathologies in which it is involved. Right ventricle is different to left ventricle in origin, anatomy, function and recovery capacity. His impedance depends on the pulmonary circulation and its involvement in respiratory diseases. left ventricle preload depends on the right ventricle, emphasizing its importance in left heart failure.

El ventrículo derecho (VD) ha sido tradicionalmente poco valorado, al concentrarse la investigación y el tratamiento de la patología cardíaca en el comportamiento del ventrículo izquierdo (VI). Desde antiguo se suponía que la importancia funcional del VD era secundaria y poco determinante. En el ámbito de las Enfermedades Respiratorias, el concepto de falla cardíaca derecha derivada de patología pulmonar o corazón pulmonar, ha estado siempre vigente, sin embargo, la limitación para efectuar las técnicas de estudio cardíaco, mantuvo distante la información disponible sobre el VD. En los últimos cinco años, ha habido un renovado interés en incrementar el conocimiento sobre el VD, produciéndose cambios significativos en lo conceptual, en los métodos de estudio y en las proyecciones de tratamiento. En este artículo revisaremos conceptos fisiopatológicos recientes, basados en publicaciones actualizadas sobre los mecanismos y patologías que comprometen el VD. Esta cavidad es marcadamente diferente del VI, tanto en su origen, como en su anatomía, función y capacidad de recuperación. Es tributario de la circulación pulmonar y dependiente de la patología respiratoria, la que es capaz de dañarlo. Además, la precarga del ventrículo izquierdo es de su dependencia, convirtiéndolo en un componente importante de su patología y de su capacidad de respuesta.

Vasorreactividad a adenosina en los pacientes con hipertensión pulmonar arterial: prevalencia y respuesta clínica, funcional y hemodinámica al tratamiento con diltiazem / Acute vasodilatador test using adenosine in patients with pulmonary arterial hypertension: prevalence and clinical, functional and hemodynamic response after diltiazem treatment

Pulmonary arterial hypertension (PAH) is a severe and progressive disease. Invasive hemodynamic study (HS) is required to confirm the diagnosis of PAH and to perform the vasodilator test (VT) with adenosine. Vasodilator acute responders (VAR) may have a sustained benefit with diltiazem. There is not national information regarding these issues. All patients with probable PAH were evaluated with HS and VT. VAR were treated with diltiazem and followed up with functional class score (FC) and 6 minute walk test. After 6 months, a second HS was performed. Results: Between 2003 and 2008, 6/54 (11%) were VAR. All were women, 45 +/- 14 years old, 4 with idiopathic PAH, 4 in FCIII and 2 in FCII. After two years of treatment, all patients clinically improved. Walked distance significantly increased by 83 and 87 m at month 12 and 24 respectively. Hemodynamic parameters also improved. Therapy with diltiazem is effective in VAR patients supporting the convenience to perform the VT.

La Hipertensión Pulmonar Arterial (HAP) es una entidad grave y progresiva. El estudio hemodinámica (EH) permite certificar el diagnóstico y evaluar la vasorreactividad mediante adenosina. Los pacientes vaso-reactivos podrían responder a terapia con diltiazem. No existe información nacional al respecto. En nuestro programa todo paciente con sospecha de HAP es sometido a EH diagnóstico y de vasorreactividad. Los positivos son tratados con diltiazem y seguidos semestralmente según capacidad funcional (CF) y con test de caminata. Al 6º mes se efectúa un 2º EH. Entre 2003-2008, 6/54 (11%) de los pacientes con HAP fueron vasorreactivos. Todas mujeres, 45 +/- 14 años, 4 con HPA idiopática, 4 en CFIII y 2 en CFII. A los 2 años, todos mejoraron clínicamente. La distancia recorrida aumentó significativamente en los meses 12 y 24 en 83 y 87 m respectivamente. Todas las variables hemodinámicas mejoraron. La terapia con diltiazem es efectiva en los pacientes vaso-reactivos lo que justifica usar el test de vasorreactividad.

Síndrome de Eisenmenger y embarazo / Eisenmenger syndrome and pregnancy

ANTECEDENTES: El embarazo está contraindicado en toda paciente con hipertensión pulmonar, y particularmente en aquellas con síndrome de Eisenmenger. OBJETIVO: Describir 3 casos de embarazadas con síndrome de Eisenmenger, tratadas con sildenafil. RESULTADOS: El desarrollo del embarazo se complicó en las tres pacientes con parto prematuro, a las 30, 28 y 35 semanas, respectivamente. En 2 pacientes el parto se resolvió mediante operación cesárea. No hubo mortalidad materna ni perinatal. CONCLUSIÓN: El síndrome de Eisenmenger es de alto riesgo de morbimortalidad materno-perinatal y el manejo multidisciplinario optimiza los resultados. Se describe el uso de sildenafil.

BACKGROUND: Pregnancy in contraindicated in patient with pulmonary hypertension, especially in dose with Eisenmenger syndrome. OBJECTIVE: To present 3 cases of pregnancy in patients with Eisenmenger syndrome treated with sildenafil. RESULTS: The pregnancy becomes complicated in the 3 cases, with premature delivery at 30, 28 and 35 weeks respectively. Cesarean delivery was performed in two cases. There was no maternal or perinatal mortality. CONCLUSION: The Eisenmenger syndrome is a high risk condition of maternal-perinatal morbimortality and the multidisciplinary handling optimizes the results. The sildenafil use is described.

[Update in the diagnosis and therapy for pulmonary arterial hypertension]. / Actualización en el diagnóstico y terapéutica en hipertensión pulmonar arterial.

Pulmonary Arterial Hypertension includes a heterogeneous group of disorders with a common genetic, pathological and hemodinamyc origin. It is characterized by a high pulmonary artery pressure due to a primary vascular disease, as a consequence of genetic and environmental factors. The common pathway is a vascular imbalance towards vasoconstriction and proliferation inside the small vessels. According to the World Health Organization, 2003, Pulmonary Arterial Hypertension is classified as idiopathic, familiar or associated to connective tissue diseases, HIV, drugs, porto-pulmonary hypertension, congenital intracardiac shunts and others. The diagnosis is based in hemodynamics. Echocardiogram is a non invasive and right ventricular catheterization is an invasive diagnostic tool. Follow up is based on a clinical and functional assessment through functional class classification, dyspnea scores and 6-minute walking test. The prognosis is historically devastating but new therapies are changing the natural history of the disease. New treatments have demonstrated improvement in symptoms, hemodynamic profiles and survival. Intravenous, subcutaneous or inhaled prostanoids such as Epoprostenol, Treprostinil or Iloprost respectively have been approved for Pulmonary Arterial Hypertension treatment as well as oral endothelial receptor blockers. They are all considered first line treatments for arterial pulmonary hypertensive patients with even better benefits than lung transplantation. Phosphodiesterase inhibitors (Sildenafil), have been recently approved for the treatment of pulmonary arterial hypertension.

Actualización en el diagnóstico y terapéutica en hipertensión pulmonar arterial / Update in the diagnosis and therapy for pulmonary arterial hypertension

Pulmonary Arterial Hypertension includes a heterogeneous group of disorders with a common genetic, pathological and hemodinamyc origin. It is characterized by a high pulmonary artery pressure due to a primary vascular disease, as a consequence of genetic and environmental factors. The common pathway is a vascular imbalance towards vasoconstriction and proliferation inside the small vessels. According to the World Health Organization, 2003, Pulmonary Arterial Hypertension is classified as idiopathic, familiar or associated to connective tissue diseases, HIV, drugs, porto-pulmonary hypertension, congenital intracardiac shunts and others. The diagnosis is based in hemodynamics. Echocardiogram is a non invasive and right ventricular catheterization is an invasive diagnostic tool. Follow up is based on a clinical and functional assessment through functional class classification, dyspnea scores and 6-minute walking test. The prognosis is historically devastating but new therapies are changing the natural history of the disease. New treatments have demonstrated improvement in symptoms, hemodynamic profiles and survival. Intravenous, subcutaneous or inhaled prostanoids such as Epoprostenol, Treprostinil or Iloprost respectively have been approved for Pulmonary Arterial Hypertension treatment as well as oral endothelial receptor blockers. They are all considered first line treatments for arterial pulmonary hypertensive patients with even better benefits than lung transplantation. Phosphodiesterase inhibitors (Sildenafil), have been recently approved for the treatment of pulmonary arterial hypertension.

[Clinical, functional and hemodynamic features of patients with pulmonary arterial hypertension]. / Caracterización clínica, funcional y hemodinámica de la población con hipertensión pulmonar arterial evaluada en el Instituto Nacional del Tórax.

BACKGROUND: Pulmonary Arterial Hypertension is a rare, progressive and devastating disease with severe consequences in quality of life and survival. AIM: A clinical, functional and hemodynamic assessment of patients with pulmonary arterial hypertension and categorization according to severity. MATERIAL AND METHODS: Prospective registry of patients with arterial pulmonary hypertension, hemodynamically defined. Clinical evaluation was performed using World Health Organization functional score (I to IV) and Borg dyspnea scale. Six minute walking test, echocardiography and right heart catheterization were used for functional and hemodynamic assessment. Intravenous Adenosine was used to assess vascular reactivity during the hemodynamic evaluation. RESULTS: Twenty nine patients were included (25 women, age range 16-72 years). Pulmonary hypertension was idiopathic in 11, associated to connective tissue disease in seven, associated to congenital heart disease in nine and associated to chronic thromboembolism in two. The mean lapse of symptoms before assessment was 2.9 years and 100% had dyspnea (Borg 5.1). Functional class I, II, III and IV was observed in 0, 5, 21 and 3 patients respectively. Six minutes walking test was 378+/-113 m. Mean pulmonary pressure was 59.4+/-12.2 mmHg, cardiac index was 2.57+/-0.88 and pulmonary vascular resistance index: 1798.4+/-855 (dyne.sec)/cm5. Nine patients had a mean pulmonary arterial pressure >55 mmHg and a cardiac index <2.1, considered as bad prognosis criteria. Adenosine test was positive in 17%. CONCLUSIONS: This group of patients with Pulmonary Arterial Hypertension was mainly conformed by young females, with a moderate to severe disease.

Caracterización clínica, funcional y hemodinámica de la población con hipertensión pulmonar arterial evaluada en el Instituto Nacional del Tórax / Clinical, functional and hemodynamic features of patients with pulmonary arterial hypertension

Background: Pulmonary Arterial Hypertension is a rare, progressive and devastating disease with severe consequences in quality of life and survival. Aim: A clinical, functional and hemodynamic assessment of patients with pulmonary arterial hypertension and categorization according to severity. Material and methods: Prospective registry of patients with arterial pulmonary hypertension, hemodynamically defined. Clinical evaluation was performed using World Health Organization functional score (I to IV) and Borg dyspnea scale. Six minute walking test, echocardiography and right heart catheterization were used for functional and hemodynamic assessment. Intravenous Adenosine was used to assess vascular reactivity during the hemodynamic evaluation. Results: Twenty nine patients were included (25 women, age range 16-72 years). Pulmonary hypertension was idiopathic in 11, associated to connective tissue disease in seven, associated to congenital heart disease in nine and associated to chronic thromboembolism in two. The mean lapse of symptoms before assessment was 2.9 years and 100% had dyspnea (Borg 5.1). Functional class I, II, III and IV was observed in 0, 5, 21 and 3 patients respectively. Six minutes walking test was 378±113 m. Mean pulmonary pressure was 59.4±12.2 mmHg, cardiac index was 2.57±0.88 and pulmonary vascular resistance index: 1798.4±855 (dyne.sec)/cm5. Nine patients had a mean pulmonary arterial pressure >55 mmHg and a cardiac index <2.1, considered as bad prognosis criteria. Adenosine test was positive in 17%. Conclusions: This group of patients with Pulmonary Arterial Hypertension was mainly conformed by young females, with a moderate to severe disease.

Studies of the transition cow under a pasture-based milk production system: metabolic profiles.

This study describes the effect of parity (multiparous versus primiparous) and body condition score (BCS) at calving (<3 or > or =3; scale 1-5) on variations of BCS, body weight (BW) and metabolic profiles in Holstein cows grazing on improved pastures. Forty-two cows were studied (21 multiparous and 21 primiparous) from 2 months before to 3 months after calving. BCS, BW and milk production were measured every 2 weeks. Blood samples were taken every 2 weeks to determine total protein, albumin, urea, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), cholesterol, aspartate aminotransferase (AST), calcium, phosphorus and magnesium. Primiparous cows had lower BCS during the early postpartum (PP) period and produced less milk than multiparous. In primiparous cows NEFA concentrations were higher during the early postpartum period; BHB levels were similar in both categories during this period. Primiparous cows showed a more unbalanced metabolic profile than multiparous cows, reflecting that they are recovering from the loss of BCS after calving with less success.

Valvuloplastía percutánea: una década de progreso continuo / Percutaneous valvuloplasty: a decade of continuous progress

Percutaneous ballon valvuloplasty is an interventional procedure designed to treat valve stenosis. The indications, techniques and results depend on the valve being opened. it is currently the treatment of choice for pulmonary valve stenosis. It is an excellent alternative to sugery for mitral stenosis in patients with mobile valves and little abnormality of the subvalvular apparatus. In aortic stenosis it constitutes a gratifying palliative procedure in older patients at high surgical risk. Longer observation is needed to better appreciate the results and indications of ballons valvuloplasty

Función diastólica de ventrículo izquierdo: evaluación comparativa entre ventriculografía radioisotópica y angiografía contrastada / Diastolic dysfunction on the left ventricle: a comparison of radioisotopic and angiograhic evaluation in patients with coronary artery disease

La evaluación de la función diastólica del ventrículo izquierdo (FDVI), que clásicamente se ha derivado del estudio hemodinámico invasivo, ha adquirido una gran importancia clínica en los últimos años. Diversas cardiopatías pueden presentar alteraciones del llenado ventricular, en forma aislada o antes de su evolución hacia la disfunción sistólica. Sin embargo, el estudio invasivo de la FDVI no es fácil. En nuestro medio existe aún poca experiencia con los métodos no invasivos disponibles en la actualidad para el estudio del diástole, entre los cuales se encuentra la ventriculografía radioisotópica (VRI). Se presentan los resultados de la evaluación del llene diastólico del v. izquierdo mediante VRI gatillada y análisis de Fourler, en un grupo de 14 cardiópatas coronarios con función sistólica conservada. Se determina en la ventriculografía contrastada la velocidad máxima de llene del v. izquierdo (VMax), la que se compara favorablemente con los datos obtenidos del estudio isotópico (VMax) y el tiempo en alcanzarla (TVMax). El 86% de los pacientes tiene disfunción diastólica. El grado de correlación entre ambas técnicas es aceptable (r = 0,61) y el nivel de concordancia es alto (86%). De acuerdo a estos resultados, consideramos que la ventriculografía isotópica es una herramienta útil, fácil y reproducible en el estudio seriado del llene ventricular

Función ventricular segmentaria en valvulopatías / Segmental ventricular function in patients with valvular heart disease

La frecuencia con que existen alteraciones segmentarias de la función ventricular (FVS) en las valvulopatías y su relación con la función sistólica global, son poco conocidas. Con el fin de aclarar este punto estudiamos 110 pacientes con patología valvular pura (22 estenosis aórtica, 24 estenosis mitral, 34 insuf. aórtica y 30 insuficiencia mitral) que tenían ventriculografía de contraste de buena calidad técnica, comparándolos con 19 normales (estudio invasivo por dolor torácico que resultó normal). Todos los pacientes sobre 45 años tenían coronariografía normal. Estudiamos el % de cambio de área segmentaria (% AS) en la región anterobasal (AB), anterolateral (AL), apical (AP), inferior (IN) e inferobasal (IB). Usamos la relación entre % AS y el % de cambio de área global. Definimos como alteración segmentaria a un índice menor a dos desviaciones estándar del promedio de los normales, para cada segmento. De los 550 segmentos analizados, existieron 14 anormales en AB, 37 en AL, 23 en AP, 11 en IN y 8 en IB (p<0.001). En conclusión: las alteraciones de la FVS son frecuentes en las valvulopatías, tienen mayor incidencia en los segmentos AL y AP y coexisten más frecuentemente con disfunción global del ventrículo izquierdo