RESUMEN
Exosomes are small extracellular vesicles, ranging in size from 30-150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes have been extensively studied and found to play a crucial role in regulating intercellular communication, thereby influencing the development and progression of numerous diseases. Traditional Chinese medicine has employed plant-based remedies for thousands of years, and an increasing body of evidence suggests that plant-derived exosome-like nanovesicles (PELNs) share similarities with mammalian-derived exosomes in terms of their structure and function. In this review, we provide an overview of recent advances in the study of PELNs and their potential implications for human health. Specifically, we summarize the roles of PELNs in respiratory, digestive, circulatory, and other diseases. Furthermore, we have extensively investigated the potential shortcomings and challenges in current research regarding the mechanism of action, safety, administration routes, isolation and extraction methods, characterization and identification techniques, as well as drug-loading capabilities. Based on these considerations, we propose recommendations for future research directions. Overall, our review highlights the potential of PELNs as a promising area of research, with broad implications for the treatment of human diseases. We anticipate continued interest in this area and hope that our summary of recent findings will stimulate further exploration into the implications of PELNs for human health.
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Exosomas , Vesículas Extracelulares , Humanos , Animales , Comunicación Celular , Medicina Tradicional China , Circulación Pulmonar , MamíferosRESUMEN
This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control.
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Aterosclerosis , Cardiología , Embolia Pulmonar , Biología , Estudios de Seguimiento , Humanos , Circulación Pulmonar , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiología , Embolia Pulmonar/terapia , Calidad de Vida , Función Ventricular DerechaRESUMEN
Importance: The recognition of the pulmonary circulation is a complex evolution in medical history and draws on theories across eras and cultures. Observations: This narrative review summarizes evidence suggesting that the recognition of pulmonary circulation is older than the time of Ibn Nafis. The theory of pulmonary circulation originated in ancient Persia (ad 224-637), was overshadowed by Greek theory from the 11th century, and reestablished by Ibn Nafis in the 13th century. Conclusions and Relevance: The findings of this review may help contextualize the story of the discovery of pulmonary circulation in ancient Persian and Greek theories before Ibn Nafis.
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Cardiología/historia , Circulación Pulmonar/fisiología , Grecia , Historia del Siglo XV , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia Antigua , Historia Medieval , Humanos , PersiaRESUMEN
BACKGROUND: The purpose of this study is to explore the association between extravascular lung water (EVLW) and prognosis of sepsis (PS). METHODS: We will carry out comprehensive literature search in electronic databases (PUBMED/MEDLINE, EMBASE, CENTRAL, WorldSciNet, PsycINFO, Allied and Complementary Medicine Database, CBM, and CNKI) and additional sources. All electronic databases will be searched from their initial to the present without language restrictions. Case-controlled studies reporting the association between EVLW and PS will be evaluated for inclusion. Outcomes of interest will include mortality rate, extravascular lung water index, pulmonary vascular permeability index, blood lactate clearance, oxygenation index, blood gas analysis, PaO2/FiO2, cardiac output index, global end diastolic volume index, intrathoracic blood volume index, systemic resistance index, acute physiology and chronic health scoring system II, and infection-related organ failure scoring system. Study quality will be evaluated using Newcastle-Ottawa Tool, and statistical analysis will be performed utilizing RevMan 5.4 software. RESULTS: This study will summarize the most recent evidence to investigate the association between EVLW and PS. CONCLUSIONS: The results of this study will provide an exhaustive view of the association between EVLW and PS. STUDY REGISTRATION OSF: osf.io/vhnxw.
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Agua Pulmonar Extravascular/metabolismo , Sepsis/mortalidad , Sepsis/fisiopatología , APACHE , Análisis de los Gases de la Sangre , Presión Sanguínea , Permeabilidad Capilar , Gasto Cardíaco , Estudios de Casos y Controles , Humanos , Ácido Láctico/sangre , Puntuaciones en la Disfunción de Órganos , Consumo de Oxígeno , Pronóstico , Circulación Pulmonar , Proyectos de Investigación , Medición de Riesgo , Factores de Riesgo , Revisiones Sistemáticas como AsuntoRESUMEN
Perinatal hypoxia induces permanent structural and functional changes in the lung and its pulmonary circulation that are associated with the development of pulmonary hypertension (PH) in later life. The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and is implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear. Pregnant C57/BL6 dams were placed in hyperbaric (760 mmHg) or hypobaric chambers during gestation (505 mmHg, day 15 through postnatal day 4) or from weaning through adulthood (420 mmHg, postnatal day 21 through 8 wk). Pulmonary hemodynamics and right ventricular systolic pressure (RVSP) were measured at 8 wk. mTOR pathway proteins were assessed in fetal (day 18.5) and adult lung (8 wk). Perinatal hypoxia induced PH during adulthood, even in the absence of a sustained secondary hypoxic exposure, as indicated by reduced pulmonary artery acceleration time (PAAT) and peak flow velocity through the pulmonary valve, as well as greater RVSP, right ventricular (RV) wall thickness, and RV/left ventricular (LV) weight. Such effects were independent of increased blood viscosity. In fetal lung homogenates, hypoxia reduced the expression of critical downstream mTOR targets, most prominently total and phosphorylated translation repressor protein (4EBP1), as well as vascular endothelial growth factor, a central regulator of angiogenesis in the fetal lung. In contrast, adult offspring of hypoxic dams tended to have elevated p4EBP1 compared with controls. Our data suggest that inhibition of mTORC1 activity in the fetal lung as a result of gestational hypoxia may interrupt pulmonary vascular development and thereby contribute to the developmental programming of PH.NEW & NOTEWORTHY We describe the first study to evaluate a role for the mTOR pathway in the developmental programming of pulmonary hypertension. Our findings suggest that gestational hypoxia impairs mTORC1 activation in the fetal lung and may impede pulmonary vascular development, setting the stage for pulmonary vascular disease in later life.
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Hipoxia Fetal/complicaciones , Hipertensión Pulmonar/etiología , Pulmón/irrigación sanguínea , Pulmón/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Neovascularización Fisiológica , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteínas de Ciclo Celular/metabolismo , Modelos Animales de Enfermedad , Femenino , Hipoxia Fetal/metabolismo , Hipoxia Fetal/fisiopatología , Edad Gestacional , Hemodinámica , Oxigenoterapia Hiperbárica , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Ratones Endogámicos C57BL , Fosforilación , Embarazo , Efectos Tardíos de la Exposición Prenatal , Circulación Pulmonar , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Función Ventricular Derecha , Presión VentricularRESUMEN
Multi-energy computed tomography (MECT) refers to acquisition of CT data at multiple energy levels (typically two levels) using different technologies such as dual-source, dual-layer and rapid tube voltage switching. In addition to conventional/routine diagnostic images, MECT provides additional image sets including iodine maps, virtual non-contrast images, and virtual monoenergetic images. These image sets provide tissue/material characterization beyond what is possible with conventional CT. MECT provides invaluable additional information in the evaluation of pulmonary vasculature, primarily by the assessment of pulmonary perfusion. This functional information provided by the MECT is complementary to the morphological information from a conventional CT angiography. In this article, we review the technique and applications of MECT in the evaluation of pulmonary vasculature.
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Angiografía por Tomografía Computarizada/métodos , Hemodinámica , Hipertensión Pulmonar/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Imagen de Perfusión/métodos , Arteria Pulmonar/diagnóstico por imagen , Circulación Pulmonar , Embolia Pulmonar/diagnóstico por imagen , Humanos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/terapia , Valor Predictivo de las Pruebas , Pronóstico , Arteria Pulmonar/fisiopatología , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/terapia , Interpretación de Imagen Radiográfica Asistida por ComputadorRESUMEN
Hypoxic pulmonary vasoconstriction (HPV) is a well-characterized vascular response to low oxygen pressures and is involved in life-threatening conditions such as high-altitude pulmonary edema (HAPE) and pulmonary arterial hypertension (PAH). While the efficacy of oral therapies can be affected by drug metabolism, or dose-limiting systemic toxicity, inhaled treatment via pressured metered dose inhalers (pMDI) may be an effective, nontoxic, practical alternative. We hypothesized that a stable water-in-perfluorooctyl bromide (PFOB) emulsion that provides solubility in common pMDI propellants, engineered for intrapulmonary delivery of pulmonary vasodilators, reverses HPV during acute hypoxia (HX). Male Sprague Dawley rats received two 10-min bouts of HX (13% O2) with 20 min of room air and drug application between exposures. Treatment groups: intrapulmonary delivery (PUL) of (1) saline; (2) ambrisentan in saline (0.1 mg/kg); (3) empty emulsion; (4) emulsion encapsulating ambrisentan or sodium nitrite (NaNO2) (0.1 and 0.5 mg/kg each); and intravenous (5) ambrisentan (0.1 mg/kg) or (6) NaNO2 (0.5 mg/kg). Neither PUL of saline or empty emulsion, nor infusions of drugs prevented pulmonary artery pressure (PAP) elevation (32.6 ± 3.2, 31.5 ± 1.2, 29.3 ± 1.8, and 30.2 ± 2.5 mmHg, respectively). In contrast, PUL of aqueous ambrisentan and both drug emulsions reduced PAP by 20-30% during HX, compared to controls. IL6 expression in bronchoalveolar lavage fluid and whole lung 24 h post-PUL did not differ among cohorts. We demonstrate proof-of-concept for delivering pulmonary vasodilators via aerosolized water-in-PFOB emulsion. This concept opens a potentially feasible and effective route of treating pulmonary vascular pathologies via pMDI.
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Sistemas de Liberación de Medicamentos/métodos , Emulsiones/administración & dosificación , Fluorocarburos/administración & dosificación , Hipertensión Pulmonar/tratamiento farmacológico , Edema Pulmonar/tratamiento farmacológico , Agua/administración & dosificación , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Emulsiones/metabolismo , Fluorocarburos/metabolismo , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/metabolismo , Masculino , Fenilpropionatos/administración & dosificación , Fenilpropionatos/metabolismo , Circulación Pulmonar/efectos de los fármacos , Circulación Pulmonar/fisiología , Edema Pulmonar/diagnóstico por imagen , Edema Pulmonar/metabolismo , Piridazinas/administración & dosificación , Piridazinas/metabolismo , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento , Agua/metabolismoAsunto(s)
Angioplastia de Balón , Transfusión de Sangre Autóloga , Circulación Pulmonar , Estenosis de Arteria Pulmonar/terapia , Arteritis de Takayasu/complicaciones , Adulto , Angioplastia de Balón/efectos adversos , Transfusión de Sangre Autóloga/instrumentación , Humanos , Masculino , Estenosis de Arteria Pulmonar/diagnóstico por imagen , Estenosis de Arteria Pulmonar/etiología , Estenosis de Arteria Pulmonar/fisiopatología , Arteritis de Takayasu/diagnóstico por imagen , Resultado del Tratamiento , Dispositivos de Acceso Vascular , Grado de Desobstrucción VascularAsunto(s)
Vasos Coronarios , Medicina Arábiga , Corazón , Historia Medieval , Humanos , Circulación PulmonarRESUMEN
Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E- (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E- (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.
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Ácidos Docosahexaenoicos/sangre , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/sangre , Ácido Eicosapentaenoico/farmacología , Feto/efectos de los fármacos , Circulación Pulmonar/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Hemodinámica , Óxido Nítrico/metabolismo , Embarazo , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Ovinos , Vasodilatación/efectos de los fármacosRESUMEN
OBJECTIVES: Congenital heart disease with increased pulmonary blood flow results in progressive pulmonary vascular endothelial dysfunction and associated increased perioperative morbidity. Using our ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated progressive endothelial dysfunction associated with disruption in carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide signaling, and enhanced reactive oxygen species generation. However, potential alterations in these parameters in patients with congenital heart disease have not been investigated. The objective of this study was to test the hypothesis that children with increased pulmonary blood flow will have evidence of altered carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide levels, and increased reactive oxygen species generation. DESIGN: A prospective single-center cohort study. SETTING: A tertiary care cardiac ICU/PICU. PATIENTS: Arterial blood samples from 18 patients with congenital heart disease associated with increased pulmonary blood flow (ventricular septal defect), 20 with congenital heart disease without increased pulmonary blood flow (tetralogy of Fallot), and 10 without heart disease (controls) were obtained. INTERVENTIONS: Plasma levels of total carnitine, free carnitine, acylcarnitine, and lactate-to-pyruvate ratios, an indicator of mitochondrial function, were determined and compared. In addition, levels of superoxide and hydrogen peroxide were determined and compared in patients with ventricular septal defect and controls. Statistical analysis was performed using an unpaired t test and analysis of variance. MEASUREMENTS AND MAIN RESULTS: Baseline acylcarnitine levels (25.7 ± 13 vs 12.7 ± 8.3; p < 0.05), the acylcarnitine-to-free carnitine ratio (0.8 ± 0.1 vs 0.3 ± 0.05; p < 0.05), and the lactate-to-pyruvate ratio were higher in ventricular septal defect (27.5 ± 3.8 vs 11.1 ± 4.1, p < 0.05) than tetralogy of Fallot; there were no differences between tetralogy of Fallot and control. Superoxide and H2O2 levels were also higher in ventricular septal defect compared with controls, and NOx levels were lower in ventricular septal defect patients compared with tetralogy of Fallot and controls (p < 0.05). CONCLUSIONS: These data suggest that increased pulmonary blood flow from ventricular septal defect results in altered carnitine and mitochondrial homeostasis, decreased nitric oxide signaling, and increased reactive oxygen species production. These data are consistent with our animal data demonstrating that altered carnitine homeostasis results in mitochondrial dysfunction, increased reactive oxygen species production, and decreased bioavailable nitric oxide. Since disruption of carnitine metabolism may contribute to endothelial dysfunction, carnitine supplementation may attenuate endothelial dysfunction associated with increased pulmonary blood flow and warrants further investigation.
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Carnitina/sangre , Defectos del Tabique Interventricular/fisiopatología , Homeostasis , Circulación Pulmonar , Biomarcadores/sangre , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Femenino , Defectos del Tabique Interventricular/sangre , Humanos , Lactante , Recién Nacido , Masculino , Mitocondrias/fisiología , Óxido Nítrico/sangre , Estudios Prospectivos , Especies Reactivas de Oxígeno/sangreRESUMEN
CONTEXT: Activity of the hypothalamus - the major brain area controlling peripheral metabolism - is specifically modulated by insulin. Research in animals suggests that brain insulin action influences pancreatic insulin secretion. OBJECTIVE: We investigated the association between hypothalamic insulin sensitivity and pancreatic insulin secretion in humans. DESIGN AND SETTING: This was a clinical-experimental trial in an university hospital setting. PARTICIPANTS: 48 healthy volunteers (21 women and 27 men) were included. MAIN OUTCOME MEASURES: Insulin sensitivity of the hypothalamus was quantified by cerebral blood flow (CBF) using MRI in combination with intranasal insulin administration. On a different day, a 75g oral glucose tolerance test with glucose, insulin, and C-peptide levels measured at five time points was performed. Three established insulin secretion indices (insulinogenic index [IGI], corrected insulin response [CIR], and AUCC-peptide0-30/AUCglucose0-30) were then analyzed for correlations with hypothalamic insulin sensitivity independent of whole-body insulin sensitivity. RESULTS: Hypothalamic insulin sensitivity showed a significant association with all three investigated insulin secretion indices (IGI p=0.0043; CIR p=0.06; AUCCpep0-30/AUCgluc0-30 p=0.0179). Participants with a strong hypothalamic insulin effect (i.e. decreased CBF after intranasal insulin administration) had lower insulin secretion during the OGTT, whereas participants with hypothalamic insulin resistance had substantially higher insulin secretion. No correlations with the occipital cortex, a control region, were detected. CONCLUSIONS: Our data suggest that hypothalamic insulin resistance might contribute to pancreatic insulin hypersecretion. Alternatively, common pathogenetic mechanisms could introduce both brain insulin resistance and beta cell hypersecretion.
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Hipotálamo/diagnóstico por imagen , Insulina/administración & dosificación , Circulación Pulmonar/efectos de los fármacos , Adulto , Área Bajo la Curva , Femenino , Prueba de Tolerancia a la Glucosa , Voluntarios Sanos , Humanos , Hipotálamo/efectos de los fármacos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Lóbulo Occipital/diagnóstico por imagen , Oxígeno/sangre , Adulto JovenAsunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter , Arteria Pulmonar/anomalías , Venas Pulmonares/cirugía , Malformaciones Vasculares/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/etiología , Fibrilación Atrial/fisiopatología , Angiografía por Tomografía Computarizada , Técnicas Electrofisiológicas Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Circulación Pulmonar , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/fisiopatología , Resultado del Tratamiento , Malformaciones Vasculares/diagnóstico por imagenRESUMEN
Human urine is currently the subject of biomedical investigations as a potential therapeutic resource and it continues to be used in remedies in different cultures and societies, including the Spanish culture. In this study we gather etnomedical knowledge about urotherapy and determine their associated symbolisms in Spain. A literature overview and a case study were carried out to compile urine-based remedies and as a direct analysis of symbolic systems. Urotherapy is widespread in Spanish folk medicine. Among the 204 collected remedies, those related to treatment of diseases or skin conditions predominate (63%). Remedies have been reported for the treatment of skin diseases such as eczema, chloasma, alopecia, etc. to treat or alleviate burns, chilblains, wounds or skin chapping, and as a treatment of venomous bites. Most of the collected remedies have an associated naturalist symbolism, based on local traditions and the transmission of empirical initial knowledge. The use of urine in Spain is a result of the interaction of two types of practice: a local and traditional urotherapy, rural and with a utilitarian purpose, and a technical urotherapy, limited to an urban environment and a naturopathic medicine.
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Fisiología/historia , Circulación Pulmonar , Catolicismo/historia , Europa (Continente) , Historia del Siglo XVI , Humanos , EspañaRESUMEN
Recent insights into the bioactivation and signaling actions of inorganic, dietary nitrate and nitrite now suggest a critical role for the microbiome in the development of cardiac and pulmonary vascular diseases. Once thought to be the inert, end-products of endothelial-derived nitric oxide (NO) heme-oxidation, nitrate and nitrite are now considered major sources of exogenous NO that exhibit enhanced vasoactive signaling activity under conditions of hypoxia and stress. The bioavailability of nitrate and nitrite depend on the enzymatic reduction of nitrate to nitrite by a unique set of bacterial nitrate reductase enzymes possessed by specific bacterial populations in the mammalian mouth and gut. The pathogenesis of pulmonary hypertension (PH), obesity, hypertension and CVD are linked to defects in NO signaling, suggesting a role for commensal oral bacteria to shape the development of PH through the formation of nitrite, NO and other bioactive nitrogen oxides. Oral supplementation with inorganic nitrate or nitrate-containing foods exert pleiotropic, beneficial vascular effects in the setting of inflammation, endothelial dysfunction, ischemia-reperfusion injury and in pre-clinical models of PH, while traditional high-nitrate dietary patterns are associated with beneficial outcomes in hypertension, obesity and CVD. These observations highlight the potential of the microbiome in the development of novel nitrate- and nitrite-based therapeutics for PH, CVD and their risk factors.
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Enfermedades Cardiovasculares/microbiología , Microbiota , Boca/microbiología , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Animales , Enfermedades Cardiovasculares/metabolismo , Ácidos Grasos/metabolismo , Humanos , Circulación Pulmonar , Transducción de SeñalRESUMEN
Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular disease. However, these measurements and the interpretation thereof are challenging due to the heterogeneous aetiology of PH in childhood and potentially confounding factors in the catheterisation laboratory. Patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease who have a cardiovascular shunt need to undergo a completely different catheterisation approach than those with idiopathic PAH lacking an anatomical cardiovascular defect. Diagnostic cardiac catheterisation of children with suspected PH usually includes right and left heart catheterisation, particularly for the initial assessment (ie, at the time of diagnosis), and should be performed in experienced centres only. Here, we present graded consensus recommendations for the invasive evaluation of children with PH including those with pulmonary hypertensive vascular disease and/or ventricular dysfunction. Based on the limited published studies and our own experience we suggest a structured catheterisation protocol and two separate definitions of positive acute vasoreactivity testing (AVT): (1) AVT to assess prognosis and indication for specific PH therapy, and (2) AVT to assess operability of PAH associated with congenital heart disease. The protocol and the latter definitions may help in the systematic assessment of these patients and the interpretation of the obtained data. Beyond an accurate diagnosis in the individual patient, such a structured approach may allow systematic decision making for the initiation of a specific treatment and may assist in estimating disease progression and individual prognosis.
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Cateterismo Cardíaco/métodos , Hipertensión Pulmonar/diagnóstico , Arteria Pulmonar/fisiopatología , Administración por Inhalación , Adolescente , Anestesia General , Anestesia Local , Niño , Sedación Consciente , Consenso , Manejo de la Enfermedad , Cardiopatías Congénitas/complicaciones , Hemodinámica , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/terapia , Iloprost , Óxido Nítrico , Oxígeno , Pronóstico , Circulación Pulmonar , Respiración Artificial , Resistencia Vascular/fisiología , Vasodilatadores , Función VentricularRESUMEN
Obesity is pandemic in the Western Hemisphere, especially in the United States (US) and is associated with morbidity and mortality. Recent data show that a large proportion of the US population is at least overweight and almost 2 in 5 Americans are obese. This ongoing trend of increasing obesity rates has led to a thriving market for anorexigens. Despite the health benefits of weight loss, several anorexigens had devastating side effects including pulmonary vascular disease which manifests as the clinical syndrome of pulmonary arterial hypertension (PAH). PAH is an incurable and fatal disease and is characterized by vascular constriction, hypertrophy, and proliferation that over time lead to right-sided cardiac failure. Over the past few decades, several weight loss medications have been associated with the development of PAH, possibly caused by an increase in systemic serotonin levels, resulting in vasoconstriction of the pulmonary arteries and initiating a cascade of pathologic vascular remodeling leading to vascular fibrosis. Once sufficient evidence for the association of these drugs with PAH or other related pathologies was found, many were removed from the market. However, there are other appetite suppressants still currently on the market (whether Food and Drug Administration-approved or "dietary supplements") that have to some extent similar mechanisms of action to those associated with PAH but lack robust enough data to prove or disprove an association. The serotonin pathway seems to be repeatedly implicated. In conclusion, given that PAH is a progressive and debilitating disease, it is important to highlight possible risk factors that could be avoided.