Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Mais filtros

Intervalo de ano de publicação
Basic Res Cardiol ; 114(2): 5, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635778


There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5 mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7 WU m2, P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0 mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7 WU m2, P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect.

Denervação/métodos , Hipertensão Pulmonar , Artéria Pulmonar/inervação , Artéria Pulmonar/cirurgia , Animais , Modelos Animais de Doenças , Distribuição Aleatória , Suínos , Pesquisa Médica Translacional
Artigo em Inglês | MEDLINE | ID: mdl-27601365


BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). METHODS AND RESULTS: To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. CONCLUSIONS: Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation.

Cardiomiopatias/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Direita/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Circulação Pulmonar , Função Ventricular Esquerda , Função Ventricular Direita , Remodelação Ventricular , Adaptação Fisiológica , Animais , Biópsia , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Hemodinâmica , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Masculino , Valor Preditivo dos Testes , Sus scrofa , Fatores de Tempo , Tomografia Computadorizada por Raios X
Basic Res Cardiol ; 111(4): 49, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27328822


Beta-3 adrenergic receptor (ß3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of ß3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of ß3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of ß3AR mRNA and the vasodilator response of ß3AR agonists in pulmonary arteries. Single intravenous administration of the ß3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different ß3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of -2.0 Wood units/m(2) for BRL37344 vs. +1.5 for vehicle, p = 0.04; and -1.8 Wood units/m(2) for mirabegron vs. +1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in ß3AR agonists-treated pigs. ß3AR was expressed in human pulmonary arteries and ß3AR agonists produced vasodilatation. ß3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH.

Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Hipertensão Pulmonar/metabolismo , Receptores Adrenérgicos beta 3/metabolismo , Resistência Vascular/efeitos dos fármacos , Acetanilidas/farmacologia , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Masculino , Nebivolol/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Tiazóis/farmacologia , Remodelação Ventricular/efeitos dos fármacos
Infectio ; 20(1): 53-55, ene.-mar. 2016. ilus, tab
Artigo em Espanhol | LILACS-Express | ID: biblio-953961


El síndrome por deleción 22q11 (SD22q11) es el síndrome por deleción cromosómica más frecuente en humanos y se caracteriza por la tríada clínica que incluye cardiopatía congénita, hipocalcemia e inmunodeficiencia primaria. El 85-90% de los pacientes tienen microdeleciones en el cromosoma 22q11.2. Tomando como punto cardinal la cardiopatía congénita, se diseñó una estrategia para tamización y diagnóstico de SD22q11 con énfasis en la evaluación inmune. Es imprescindible realizar una historia clínica detallada y, posteriormente, un análisis cuantitativo y funcional de las subpoblaciones de linfocitos en sangre periférica para clasificarlo en SD22q11 completo (<1%) o parcial (95-99%) e instaurar las pautas de tratamiento en aspectos como: aislamiento del paciente, vacunación, profilaxis contra microorganismos oportunistas, uso de productos sanguíneos irradiados y reconstitución inmunológica. Sin embargo, el abordaje del paciente debe ser multidisciplinario para detectar y prevenir complicaciones a largo plazo que pueden ser graves, especialmente en los pacientes con SD22q11 completo.

In humans, 22q11 deletion syndrome (22q11DS) is considered the most common chromosome deletion syndrome. It is characterised by a clinical triad that includes congenital heart disease, hypocalcaemia and primary immunodeficiency. Approximately 85-90% of patients with this syndrome exhibit microdeletions in chromosome 22q11.2. Using congenital heart disease as a starting point, we designed a strategy for the screening and diagnosis of 22q11DS with an emphasis on immunological evaluation. A detailed clinical history and the subsequent quantitative and functional analyses of the lymphocyte subpopulations in the peripheral blood is crucial to classify as complete (<1%) or partial (95-99%) the disease and to guide clinicians in terms of patient isolation, vaccination, prophylaxis for opportunistic infections, use of irradiated blood products and immunological reconstitution. However, multidisciplinary care is necessary to detect and prevent long-term complications that could be severe, particularly in cases of complete 22q11DS.