RESUMEN
Fundamento: O tempo de aceleração na artéria pulmonar (TAP) pode ser utilizado para avaliação da hipertensão pulmonar na análise da função diastólica do ventrículo esquerdo. Objetivo: Avaliar se existe correlação entre o valor do tempo de aceleração na artéria pulmonar e parâmetros da função diastólica do ventrículo esquerdo em indivíduos com função sistólica do ventrículo esquerdo preservada e de acordo com sexo, idade e fatores de risco cardiovasculares. Métodos: Estudo observacional, transversal. Foram selecionados 119 pacientes (59 mulheres; 49,6%). Os indivíduos foram submetidos ao ecocardiograma transtorácico incluindo os valores de tempo de aceleração na artéria pulmonar; ondas E e A e relação E/A ao Doppler espectral do influxo mitral; ondas e' septal, e' lateral e relação E/e' ao Doppler tecidual do anel mitral; pressão sistólica na artéria pulmonar e volume atrial esquerdo. Resultados: No sexo feminino, foi encontrada correlação positiva (coeficiente de correlação de Spearman) entre o valor do tempo de aceleração na artéria pulmonar e e' lateral (coeficiente de correlação de Spearman de 0,47; p=0,002), relação E/A (coeficiente de correlação de Spearman de 0,32; p=0,04) e e' septal (coeficiente de correlação de Spearman de 0,36; p=0,023) e uma correlação negativa entre o valor do tempo de aceleração na artéria pulmonar e pressão sistólica na artéria pulmonar (coeficiente de correlação de Spearman de -0,43; p=0,034). No sexo masculino, não foi encontrada correlação significativa. Foram encontrados menores valores de tempo de aceleração na artéria pulmonar em mulheres com hipertensão arterial sistêmica quando comparadas a mulheres sem hipertensão arterial sistêmica (0,13±0,03 segundos versus 0,16±0,03 segundos; p = 0,015). Conclusão: O presente estudo mostrou correlação significativa dos valores do TAP com alguns parâmetros da função diastólica do ventrículo esquerdo apenas no sexo feminino, sendo que mulheres hipertensas apresentaram menores valores de TAP. (AU)
Background: Pulmonary artery acceleration time (PAAT) can be used as a parameter in the evaluation of pulmonary hypertension and aids left ventricular diastolic function (LVDF) analyses. Objective: To assess whether there is a correlation between PAAT and LVDF parameters in individuals with a preserved left ventricular systolic function and by sex, age, and cardiovascular risk factors. Method: Observational cross-sectional study. One hundred nineteen patients were selected (59 women [49.6%]). The subjects underwent transthoracic echocardiography including measurements of PAAT, E and A waves and E/A ratio, e' septal and e' lateral waves and E/e' ratio, pulmonary artery systolic pressure (PASP), and left atrial volume. Results: In female patients, a positive correlation (Spearman's correlation coefficient Spearman correlation coefficient [SCC]) was found between the PAAT value and the lateral e' (SCC, 0.47; p = 0.002), with the E/A ratio (SCC, 0.32; p = 0.04), and with septal e' (SCC, 0.36; p = 0.023), and a negative correlation between PAAT and PASP (SCC, -0.43; p = 0.034). In men, no correlation was found between PAAT. and any parameters. Lower PAAT values were found in women with systemic arterial hypertension (hypertension) than in women without hypertension (0.13 ± 0.03 s versus 0.16 ± 0.03 s; p = 0.015). Conclusion: The present study showed a significant correlation between PAAT and some LVDF parameters in female patients only. Hypertension was correlated with lower PAAT values in women. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Arteria Pulmonar/fisiología , Ventrículos Cardíacos/anomalías , Hipertensión Pulmonar/diagnóstico , Tabaquismo/complicaciones , Enfermedad de la Arteria Coronaria/complicaciones , Ecocardiografía/métodos , Estadísticas no Paramétricas , Ecocardiografía Doppler de Pulso/métodos , Dislipidemias/complicaciones , Factores de Riesgo de Enfermedad CardiacaRESUMEN
Exposure to secondhand cigarette smoke is associated with the development of diverse diseases. Resistance training has been considered one of the most useful tools for patients with pulmonary disease, improving their quality of life. This study aimed to evaluate the effect of resistance training (RT) on the prevention of thickening of the right ventricle wall of rats exposed to secondhand cigarette smoke. Thirty-two Wistar rats were divided into four groups: Control (C), Smoker (S), Exercised (E) and Exercised Smoker (ES). The smoker groups were exposed to the smoke of four cigarettes for 30 min, twice daily, five days a week, for 16 weeks. The exercised groups climbed on a vertical ladder with progressive load, once a day, five days a week, for 16 weeks. The heart, trachea, lung, liver and gastrocnemius muscle were removed for histopathological analysis. Pulmonary emphysema (S and ES vs C and E, P < 0.0001) and pulmonary artery thickness enlargement (S vs C and E, P = 0.003, ES vs C, P = 0.003) were detected in the smoking groups. There was an increase in the right ventricle thickness in the S group compared with all other groups (P < 0.0001). An increase in resident macrophages in the liver was detected in both smoking groups compared with the C group (P = 0.002). Additionally, a relevant reduction of the diameter of the muscle fibers was detected only in ES compared with the C, S and E groups (P = 0.0002), impairing, at least in part, the muscle mass in exercised smoking rats. Therefore, it was concluded that resistance training prevented the increase of thickness of the right ventricle in rats exposed to secondhand cigarette smoke, but it may be not so beneficial for the skeletal muscle of smoking rats.
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Fumar Cigarrillos/efectos adversos , Hipertrofia Ventricular Derecha/prevención & control , Condicionamiento Físico Animal/métodos , Contaminación por Humo de Tabaco/efectos adversos , Animales , Fumar Cigarrillos/patología , Fumar Cigarrillos/fisiopatología , Modelos Animales de Enfermedad , Humanos , Hipertrofia Ventricular Derecha/patología , Hipertrofia Ventricular Derecha/fisiopatología , Masculino , Músculo Esquelético/patología , Arteria Pulmonar/fisiología , Enfisema Pulmonar/etiología , Enfisema Pulmonar/patología , Enfisema Pulmonar/fisiopatología , Ratas , Ratas Wistar , Entrenamiento de FuerzaRESUMEN
Pulmonary arterial pressure (PAP) is a diagnostic measure used to determine an individual's susceptibility to developing high-altitude disease. The importance of PAP measures collected at elevations lower than the intended breeding elevation of the bulls (i.e., ≥1,520 m) is unknown. Therefore, the objective of this study was to determine the genetic relationship between PAP measures collected in a range of elevations using reaction norm models. A total of 9,177 PAP and elevation observations on purebred Angus cattle, which averaged 43.49 ± 11.32 mmHg and 1,878.6 ± 296.8 m, respectively, were used in the evaluation. The average age of the individuals in the evaluation was 434.04 ± 115.9 d. A random regression model containing the effects of sex, a linear covariate of age, a quadratic fixed covariate of elevation, and random effects consisting of a contemporary group and a linear regression of PAP on elevation was used for the evaluation of PAP. Two forms of PAP were evaluated with this model. First, to address the non-normality of the data, PAP was raised to the power of -2.6 (ptPAP) based on the results of a Box-Cox analysis. Second, raw PAP (rPAP) phenotypes were evaluated to compare the results to those obtained from the transformed data. For ptPAP, heritability ranged from 0.25 to 0.37 corresponding to elevations of 1,900 and 1,215 m, respectively. For rPAP, heritability ranged from 0.22 to 0.41 corresponding to elevations of 1,700 and 2,495 m, respectively. Generally, lower elevations corresponded to decreased heritabilities while higher elevations corresponded to increased heritability estimates. For ptPAP, genetic correlations ranged from 0.18 (elevation: 1,215 and 2,495 m) to 1.00. For rPAP, genetic correlations ranged from 0.08 (elevation: 1,215 and 2,495 m) to 1.00. In general, the closer the elevations in which PAP was measured, the greater the genetic relationship. The greater the difference in elevation between PAP measures resulted in lower genetic correlations. The rank correlation between expected progeny differences (EPD) for 1,215 and 2,495 m was 0.65 and 0.49 for the ptPAP and rPAP, respectively. These results suggested that PAP measures collected in lower elevations may be used as an indicator of high-altitude adaptability. In the estimation of EPD to rank sires for their suitability for use in high-elevation production systems, it is important to account for the relationships among varied altitudes.
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Presión Arterial/fisiología , Bovinos/fisiología , Modelos Estadísticos , Altitud , Animales , Cruzamiento , Bovinos/genética , Femenino , Modelos Lineales , Masculino , Fenotipo , Arteria Pulmonar/fisiologíaRESUMEN
The purpose of calculating the capillary filtration coefficient is to experimentally evaluate edema formation in models of pulmonary ischemia-reperfusion injury. For many years, the obtaining of this coefficient implies a series of manual maneuvers during ex-vivo reperfusion of pulmonary arterial pressure, venous pressure and weight, as well as the calculation of the Kfc formula. Through automation, the calculation of capillary filtration coefficient could be easier and more efficient. To describe an automatic method designed in our laboratory to calculating the capillary filtration coefficient and compare with traditional determination of capillary filtration coefficient as gold standard method. An automatic three valve perfusion system was constructed, commanded by a mastery module connected to a graphical user interface. To test its accuracy, cardiopulmonary blocks of Wistar rats were harvested and distributed in manual (n=8) and automated (n=8) capillary filtration coefficient determination groups. Physiological parameters as pulmonary arterial pressure, pulmonary venous pressure, weight and capillary filtration coefficient were obtained. Results: Capillary filtration coefficient, pulmonary arterial pressure, venous arterial pressure shown no statistical significance difference between the groups. The automated perfusion system for obtaining Kfc was standardized and validated, giving reliable results without biases and making the process more efficient in terms of time and personal staff.
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Capilares/fisiología , Permeabilidad Capilar/fisiología , Perfusión/métodos , Arteria Pulmonar/fisiología , Venas Pulmonares/fisiología , Animales , Técnicas de Cultivo de Órganos , Perfusión/instrumentación , Presión Esfenoidal Pulmonar/fisiología , Ratas , Ratas WistarRESUMEN
RESUMEN: Antecedentes: La presión media arterial pulmonar (PMAP) es una variable hemodinámica indispensable para el diagnóstico, clasificación y pronóstico de la Hipertensión Pulmonar (HP). Su cuantificación se realiza en forma invasiva por cateterismo cardíaco derecho (CCD) y no invasivamente por ecocardiografía Doppler. Masuyama propuso su medición mediante el gradiente transvalvular pulmonar diastólico derivado de la velocidad máxima inicial de la regurgitación pulmonar (∆RPi2) correspondiendo cercanamente a la medición invasiva. Objetivos: Revalidar 3 métodos ecocardiográficos que estiman la PMAP y valorar la utilidad del método de Chemla en el Test de Reactividad Vascular Pulmonar (TRVP). Métodos: Estudio prospectivo, observacional, doble ciego divido en dos etapas. A) o I) 30 pacientes se realizó ecocardiografía Doppler diagnóstica en nuestro centro. Se midieron regurgitación tricuspídea (RT) y tiempo de aceleración pulmonar (TAP) para derivar las siguientes ecuaciones: 1) 0.61xPSAP+1.95 (Chemla) 2) Gradiente presión media RT (∆PmRT) +PAD (presión-aurícula derecha) (Aduen) y 3) 79-0.45xTAP o 90-0.60xTAP, según sea el valor del TAP. B) o II) 10 pacientes enrolados para realizar el TRVP comparando la medición ecocardiográfica (Chemla) con CCD. Resultados: En la primera parte del estudio se encontró alta correlación entre las 3 ecuaciones: ChemlaAduen, R2=0.91; Chemla-Kitabatake, R2=0.87; Aduen-Kitabatake, R2=0,91. En la segunda parte comparando la PMAP-Chemla y Cateterismo derecho (CD) obtuvimos alta correlación: en tiempo 0, 30 min y recuperación:(R2=0.87, 0.99, 0.98, respectivamente). Ambas partes del estudio mostraron límites de concordancia satisfactoria con valor medio de la diferencia entre los métodos cercano a 1 en el t30 y tR del TRVP. Conclusión: los métodos dependientes de la medición de la RT son efectivos y confiables para estimar la PMAP. El método de Chemla es útil en el TRVP.
ABSTRACTS: Background: Mean Pulmonary arterial pressure (PMAP)is an indispensable hemodynamic variable for the diagnosis, classification and prognosis of Pulmonary Hypertension (PH). Its quantification is performed invasively by cardiac catheterization and non-invasively by Doppler echocardiography. Masuyama proposed its measurement by the transvalvular diastolic pulmonary gradient derived from the initial maximum velocity of pulmonary regurgitation(ΔPRi2) corresponding closely to the invasive measurement. Objectives: to compare 3 known echocardiographic methods to estimate MPAP and demonstrate the usefulness of the Chemla method in the Pulmonary Vascular Reactivity Test (PVRT). Methods: prospective, observational, double-blind study divided into two stages. A) 30 patients underwent diagnostic Doppler echocardiography. Tricuspid regurgitation (TR) and pulmonary acceleration time (PAT) were measured to derive the equations: 1) 0.61xSPAP + 1.95 (Chemla) 2) Gradient mean pressure TR (ΔPmTR) + RAP (right atrium pressure) (Aduen).3) 79-0.45xPAT o 90-0.60xPAT depending on the value of PAT. B) 10 patients enrolled to PVRT comparing the echocardiographic measurement (Chemla) with right catheterization. Results: in the first part of the study a high correlation between the 3 equations was found : ChemlaAduen, R2 = 0.91; Chemla-Kitabatake, R2=0.87; Aduen-Kitabatake, R2=0.91. In the second part comparing the MPAP-Chemla and RHC we obtained a high correlation in time 0, 30 min and recovery: (R2=0.87,0,99,0.98, respectively). Both parts of the study showed satisfactory limits concordance with mean value of the difference between the methods close to 1 in the t30 and tR of the TRVP. Conclusion: the methods dependent on the measurement of the TR are effective and reliable for estimating MPAP. The Chemla method is useful in the PVRT.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Arteria Pulmonar/fisiología , Arteria Pulmonar/diagnóstico por imagen , Circulación Pulmonar/fisiología , Hipertensión Pulmonar/diagnóstico , Resistencia Vascular , Velocidad del Flujo Sanguíneo , Cateterismo Cardíaco , Ecocardiografía Doppler/métodos , Modelos Lineales , Método Doble Ciego , Interpretación Estadística de Datos , Estudios Prospectivos , Presión Arterial/fisiología , Aceleración , Hipertensión Pulmonar/fisiopatología , Pulmón/fisiología , Pulmón/irrigación sanguíneaRESUMEN
KEY POINTS: Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. We show that high- compared to lowland newborn llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn llama. ABSTRACT: Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. The cardiopulmonary function of newborn llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.
Asunto(s)
Hipoxia/fisiopatología , Óxido Nítrico/fisiología , Altitud , Animales , Animales Recién Nacidos , Presión Arterial , Camélidos del Nuevo Mundo , Frecuencia Cardíaca , Pulmón/fisiología , Arteria Pulmonar/fisiología , Circulación Pulmonar , VasoconstricciónRESUMEN
BACKGROUND: Nitrite has been shown to reduce right ventricle (RV) remodeling in experimental pulmonary hypertension. However, whether this effect is due to a reduction in RV afterload (ie, reduction in pulmonary artery pressure) or a direct effect on the RV itself remains unanswered. We hypothesize that nitrite has direct effects on RV remodeling and studied its effects in mice with pulmonary artery banding (PAB). METHODS AND RESULTS: PAB decreased exercise tolerance and reduced RV systolic and diastolic function. Nitrite treatment attenuated the decrease in RV systolic function and improved the RV diastolic function. Nitrite-treated mice with PAB had similar exercise tolerance compared with a control group. PAB induced RV hypertrophy and fibrosis which were associated with increased expression of phospho-Akt. Interestingly, nitrite treatment attenuated PAB-induced RV hypertrophy and reduced the expression of phospho-Akt in RV tissue from mice with PAB. In neonatal rat cardiac fibroblast, nitrite also attenuated hypoxia-induced increase in expression of phospho-Akt. CONCLUSION: Our study indicates that nitrite treatment has direct beneficial effects on RV and improves function and attenuates remodeling in RV exposed to chronic pressure overload. These beneficial effects, at least in part, could be due to the inhibition of the phospho-Akt (p-Akt) pathway activation.
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Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/prevención & control , Nitritos/administración & dosificación , Arteria Pulmonar/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Células Cultivadas , Insuficiencia Cardíaca/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Arteria Pulmonar/fisiología , Disfunción Ventricular Derecha/patología , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/prevención & control , Remodelación Ventricular/fisiologíaRESUMEN
Bioengineering of functional lung tissue by using whole lung scaffolds has been proposed as a potential alternative for patients awaiting lung transplant. Previous studies have demonstrated that vascular resistance (Rv) could be altered to optimize the process of obtaining suitable lung scaffolds. Therefore, this work was aimed at determining how lung inflation (tracheal pressure) and perfusion (pulmonary arterial pressure) affect vascular resistance. This study was carried out using the lungs excised from 5 healthy male Sprague-Dawley rats. The trachea was cannulated and connected to a continuous positive airway pressure (CPAP) device to provide a tracheal pressure ranging from 0 to 15cmH2O. The pulmonary artery was cannulated and connected to a controlled perfusion system with continuous pressure (gravimetric level) ranging from 5 to 30cmH2O. Effective Rv was calculated by ratio of pulmonary artery pressure (PPA) by pulmonary artery flow (V'PA). Rv in the decellularized lungs scaffolds decreased at increasing V'PA, stabilizing at a pulmonary arterial pressure greater than 20cmH2O. On the other hand, CPAP had no influence on vascular resistance in the lung scaffolds after being subjected to pulmonary artery pressure of 5cmH2O. In conclusion, compared to positive airway pressure, arterial lung pressure markedly influences the mechanics of vascular resistance in decellularized lungs.
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Pulmón/fisiología , Arteria Pulmonar/fisiología , Resistencia Vascular , Animales , Presión de las Vías Aéreas Positiva Contínua , Insuflación , Pulmón/irrigación sanguínea , Masculino , Perfusión , Ratas Sprague-Dawley , Andamios del Tejido , TráqueaRESUMEN
CONTEXT AND OBJECTIVE: P2 hyperphonesis is considered to be a valuable finding in semiological diagnoses of pulmonary hypertension (PH). The aim here was to evaluate the accuracy of the pulmonary component of second heart sounds for predicting PH in patients with interstitial lung disease. DESIGN AND SETTING: Cross-sectional study at the University of Brasilia and Hospital de Base do Distrito Federal. METHODS: Heart sounds were acquired using an electronic stethoscope and were analyzed using phonocardiography. Clinical signs suggestive of PH, such as second heart sound (S2) in pulmonary area louder than in aortic area; P2 > A2 in pulmonary area and P2 present in mitral area, were compared with Doppler echocardiographic parameters suggestive of PH. Sensitivity (S), specificity (Sp) and positive (LR+) and negative (LR-) likelihood ratios were evaluated. RESULTS: There was no significant correlation between S2 or P2 amplitude and PASP (pulmonary artery systolic pressure) (P = 0.185 and 0.115; P= 0.13 and 0.34, respectively). Higher S2 in pulmonary area than in aortic area, compared with all the criteria suggestive of PH, showed S = 60%, Sp= 22%; LR+ = 0.7; LR- = 1.7; while P2> A2 showed S= 57%, Sp = 39%; LR+ = 0.9; LR- = 1.1; and P2 in mitral area showed: S= 68%, Sp = 41%; LR+ = 1.1; LR- = 0.7. All these signals together showed: S= 50%, Sp = 56%. CONCLUSIONS: The semiological signs indicative of PH presented low sensitivity and specificity levels for clinically diagnosing this comorbidity.
RESUMO CONTEXTO E OBJETIVO: Hiperfonese de P2 tem sido considerada como achado valoroso no diagnóstico semiológico de hipertensão pulmonar (HP). O objetivo foi de avaliar a acurácia do componente pulmonar da segunda bulha cardíaca em predizer HP nos pacientes portadores de doenças intersticiais pulmonares. TIPO DE ESTUDO E LOCAL: Estudo transversal na Universidade de Brasília e Hospital de Base do Distrito Federal. MÉTODOS: Os sons cardíacos foram adquiridos com estetoscópio eletrônico e analisados por fonocardiografia. Os sinais clínicos sugestivos de HP, como B2 mais intensamente audível em área pulmonar que aórtica, P2 > A2 na área pulmonar e P2 presente em área mitral foram confrontados com parâmetros cardiográficos no exame de Doppler sugestivos de HP. Sensibilidade (S), especificidade (E), razões de verossimilhança positiva (RV+) e negativa (RV-) foram avaliados. RESULTADOS: Não houve correlação significativa entre amplitude de B2 e P2 e a PSAP (pressão sistólica arterial pulmonar) (P = 0,185 e 0,115; P = 0,13 e 0,34; respectivamente). A análise da presença de B2 mais intensa na área pulmonar que aórtica, quando comparada a todos os critérios sugestivos de HP, mostrou S = 60%; E = 22%; RV+ = 0,7; RV- = 1,7; enquanto P2 > A2 mostrou: S = 57%; E = 39%; RV+ = 0,9; RV- = 1,1; e P2 no foco mitral mostrou: S = 68%; E = 41%; RV+ = 1,1; RV- = 0,7. Todos os sinais juntos mostraram S = 50%; E = 56%. CONCLUSÃO: Os sinais semiológicos indicativos de HP apresentam baixos valores de especificidade e sensibilidade para diagnóstico clínico dessa comorbidade.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Ruidos Cardíacos/fisiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Hipertensión Pulmonar/diagnóstico , Fonocardiografía , Arteria Pulmonar/fisiología , Ecocardiografía , Estudios Transversales , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Hipertensión Pulmonar/fisiopatologíaRESUMEN
CONTEXT AND OBJECTIVE: P2 hyperphonesis is considered to be a valuable finding in semiological diagnoses of pulmonary hypertension (PH). The aim here was to evaluate the accuracy of the pulmonary component of second heart sounds for predicting PH in patients with interstitial lung disease. DESIGN AND SETTING: Cross-sectional study at the University of Brasilia and Hospital de Base do Distrito Federal. METHODS: Heart sounds were acquired using an electronic stethoscope and were analyzed using phonocardiography. Clinical signs suggestive of PH, such as second heart sound (S2) in pulmonary area louder than in aortic area; P2 > A2 in pulmonary area and P2 present in mitral area, were compared with Doppler echocardiographic parameters suggestive of PH. Sensitivity (S), specificity (Sp) and positive (LR+) and negative (LR-) likelihood ratios were evaluated. RESULTS: There was no significant correlation between S2 or P2 amplitude and PASP (pulmonary artery systolic pressure) (P = 0.185 and 0.115; P= 0.13 and 0.34, respectively). Higher S2 in pulmonary area than in aortic area, compared with all the criteria suggestive of PH, showed S = 60%, Sp= 22%; LR+ = 0.7; LR- = 1.7; while P2> A2 showed S= 57%, Sp = 39%; LR+ = 0.9; LR- = 1.1; and P2 in mitral area showed: S= 68%, Sp = 41%; LR+ = 1.1; LR- = 0.7. All these signals together showed: S= 50%, Sp = 56%. CONCLUSIONS: The semiological signs indicative of PH presented low sensitivity and specificity levels for clinically diagnosing this comorbidity.
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Ruidos Cardíacos/fisiología , Hipertensión Pulmonar/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ecocardiografía , Femenino , Humanos , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Fonocardiografía , Valor Predictivo de las Pruebas , Arteria Pulmonar/fisiología , Sensibilidad y EspecificidadRESUMEN
Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.
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Aloinjertos/fisiología , Implantación de Prótesis Vascular/métodos , Prótesis Vascular , Criopreservación/métodos , Crioprotectores , Liofilización/métodos , Glutaral , Arteria Pulmonar , Aloinjertos/anatomía & histología , Aloinjertos/cirugía , Análisis de Varianza , Animales , Presión Sanguínea , Prótesis Vascular/efectos adversos , Perros , Femenino , Masculino , Arteria Pulmonar/patología , Arteria Pulmonar/fisiología , Circulación Pulmonar , Trasplante Homólogo , Resistencia VascularRESUMEN
Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.
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Animales , Perros , Femenino , Masculino , Aloinjertos/fisiología , Prótesis Vascular , Implantación de Prótesis Vascular/métodos , Crioprotectores , Criopreservación/métodos , Liofilización/métodos , Glutaral , Arteria Pulmonar , Análisis de Varianza , Aloinjertos/anatomía & histología , Aloinjertos/cirugía , Presión Sanguínea , Prótesis Vascular/efectos adversos , Circulación Pulmonar , Arteria Pulmonar/patología , Arteria Pulmonar/fisiología , Trasplante Homólogo , Resistencia VascularRESUMEN
Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. Perfusion of decellularizing media through the pulmonary artery has shown to be effective. How vascular perfusion pressure and flow vary throughout lung decellularization, which is not well known, is important for optimizing the process (minimizing time) while ensuring scaffold integrity (no barotrauma). This work was aimed at characterizing the pressure/flow relationship at the pulmonary vasculature and at how effective vascular resistance depends on pressure- and flow-controlled variables when applying different methods of media perfusion for lung decellularization. Lungs from 43 healthy mice (C57BL/6; 7-8 weeks old) were investigated. After excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization with a solution of 1% sodium dodecyl sulfate (SDS). Pressure (PPA) and flow (V'PA) at the pulmonary artery were continuously measured. Decellularization media was perfused through the pulmonary artery: (a) at constant PPA=20 cmH2O or (b) at constant V'PA=0.5 and 0.2 ml/min. Effective vascular resistance was computed as Rv=PPA/V'PA. Rv (in cmH2O/(ml/min)); mean±SE) considerably varied throughout lung decellularization, particularly for pressure-controlled perfusion (from 29.1±3.0 in baseline to a maximum of 664.1±164.3 (p<0.05), as compared with flow-controlled perfusion (from 49.9±3.3 and 79.5±5.1 in baseline to a maximum of 114.4±13.9 and 211.7±70.5 (p<0.05, both), for V'PA of 0.5 and 0.2 ml/min respectively. Most of the media infused to the pulmonary artery throughout decellularization circulated to the airways compartment across the alveolar-capillary membrane. This study shows that monitoring perfusion mechanics throughout decellularization provides information relevant for optimizing the process time while ensuring that vascular pressure is kept within a safety range to preserve the organ scaffold integrity.
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Bioingeniería/métodos , Pulmón/irrigación sanguínea , Pulmón/citología , Fenómenos Mecánicos , Perfusión , Presión , Arteria Pulmonar/fisiología , Animales , Fenómenos Biomecánicos , Masculino , Ratones , Ratones Endogámicos C57BL , Resistencia VascularRESUMEN
Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial- and muscular-dependent pathways. This was associated with an enhanced nitric oxide-dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.
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Antioxidantes/farmacología , Hipertensión Pulmonar/metabolismo , Pulmón/efectos de los fármacos , Melatonina/farmacología , Estrés Oxidativo/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Animales , Animales Recién Nacidos , Pulmón/irrigación sanguínea , Arteria Pulmonar/fisiología , OvinosRESUMEN
Painschab, Matthew S., Gary E. Malpartida, Victor G. Davila-Roman, Robert H. Gilman, Todd M. Kolb, Fabiola Leon-Velarde, J. Jaime Miranda, and William Checkley. Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. High Alt Med Biol 16:26-33, 2015.-Long-term residence at high altitude is associated with the development of chronic mountain sickness (CMS), which is characterized by excessive erythrocytosis (EE). EE occurs under chronic hypoxia, and a strongly selected mutation in hypoxia-inducible factor 2α (HIF2A) has been found in native Tibetans that correlates with having a normal hemoglobin at high altitude. We sought to evaluate differences in plasma levels of four HIF-responsive proteins in 20 participants with EE (hemoglobin >21 g/dL in men and >19 in women) and in 20 healthy, age- and sex-matched participants without EE living at high altitude in Puno, Peru. We performed ELISA to measure plasma levels of the four HIF-responsive proteins: vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), endothelin-1, and erythropoietin. As a secondary aim, we evaluated the association between HIF-responsive proteins and echocardiography-estimated pulmonary artery systolic pressure (PASP) in a subset of 26 participants. sVEGF-R1 was higher in participants with vs. without EE (mean 107 pg/mL vs. 90 pg/mL; p=0.007). Although plasma concentrations of endothelin-1, VEGF, and erythropoietin were higher in participants with vs. without EE, they did not achieve statistical significance (all p>0.25). Both sVEGF-R1 (p=0.04) and erythropoietin (p=0.04) were positively associated with PASP after adjustment for age, sex, and BMI. HIF-responsive proteins may play a pathophysiological role in altitude-related, chronic diseases but our results did not show consistent changes in all measured HIF-responsive proteins. Larger studies are needed to evaluate for additional genetic and environmental risk factors.
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Mal de Altura/sangre , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/sangre , Hipoxia/sangre , Policitemia/sangre , Adulto , Anciano , Altitud , Biomarcadores/sangre , Presión Sanguínea , Estudios de Casos y Controles , Endotelina-1/sangre , Eritropoyetina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perú , Arteria Pulmonar/fisiología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASSBio-1359), on monocrotaline (MCT)-induced pulmonary hypertension in rats. EXPERIMENTAL APPROACH: PAH was induced in male Wistar rats by a single i.p. injection of MCT (60 mg·kg(-1)) and 2 weeks later, oral LASSBio-1359 (50 mg·kg(-1)) or vehicle was given once daily for 14 days. Echocardiography was used to measure cardiac function and pulmonary artery dimensions, with histological assay of vascular collagen. Studies of binding to human recombinant adenosine receptors (A1, A2A, A3) and of docking with A2A receptors were also performed. KEY RESULTS: MCT administration induced changes in vascular and ventricular structure and function, characteristic of PAH. These changes were reversed by treatment with LASSBio-1359. MCT also induced endothelial dysfunction in pulmonary artery, as measured by diminished relaxation of pre-contracted arterial rings, and this dysfunction was reversed by LASSBio-1359. In pulmonary artery rings from normal Wistar rats, LASSBio-1359 induced relaxation, which was decreased by the adenosine A2A receptor antagonist, ZM 241385. In adenosine receptor binding studies, LASSBio-1359 showed most affinity for the A2A receptor and in the docking analyses, binding modes of LASSBio-1359 and the A2A receptor agonist, CGS21680, were very similar. CONCLUSION AND IMPLICATIONS: In rats with MCT-induced PAH, structural and functional changes in heart and pulmonary artery were reversed by treatment with oral LASSBio-1359, most probably through the activation of adenosine A2A receptors.
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Agonistas del Receptor de Adenosina A2/uso terapéutico , Benzamidas/uso terapéutico , Hidrazonas/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Agonistas del Receptor de Adenosina A2/farmacología , Administración Oral , Animales , Benzamidas/farmacología , Colágeno/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Hemodinámica , Hidrazonas/farmacología , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/tratamiento farmacológico , Hipertrofia Ventricular Derecha/metabolismo , Hipertrofia Ventricular Derecha/fisiopatología , Técnicas In Vitro , Masculino , Simulación del Acoplamiento Molecular , Monocrotalina , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiología , Ratas Wistar , Receptores de Adenosina A2RESUMEN
PURPOSE: To validate the use of particle traces derived from four-dimensional (4D) flow magnetic resonance (MR) imaging to quantify in vivo the caval flow contribution to the pulmonary arteries (PAs) in patients who had been treated with the Fontan procedure. MATERIALS AND METHODS: The institutional review boards approved this study, and informed consent was obtained. Twelve healthy volunteers and 10 patients with Fontan circulation were evaluated. The particle trace method consists of creating a region of interest (ROI) on a blood vessel, which is used to emit particles with a temporal resolution of approximately 40 msec. The flow distribution, as a percentage, is then estimated by counting the particles arriving to different ROIs. To validate this method, two independent observers used particle traces to calculate the flow contribution of the PA to its branches in volunteers and compared it with the contribution estimated by measuring net forward flow volume (reference method). After the method was validated, caval flow contributions were quantified in patients. Statistical analysis was performed with nonparametric tests and Bland-Altman plots. P < .05 was considered to indicate a significant difference. RESULTS: Estimation of flow contributions by using particle traces was equivalent to estimation by using the reference method. Mean flow contribution of the PA to the right PA in volunteers was 54% ± 3 (standard deviation) with the reference method versus 54% ± 3 with the particle trace method for observer 1 (P = .4) and 54% ± 4 versus 54% ± 4 for observer 2 (P = .6). In patients with Fontan circulation, 87% ± 13 of the superior vena cava blood flowed to the right PA (range, 63%-100%), whereas 55% ± 19 of the inferior vena cava blood flowed to the left PA (range, 22%-82%). CONCLUSION: Particle traces derived from 4D flow MR imaging enable in vivo quantification of the caval flow distribution to the PAs in patients with Fontan circulation. This method might allow the identification of patients at risk of developing complications secondary to uneven flow distribution. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120778/-/DC1.
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Procedimiento de Fontan , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Complicaciones Posoperatorias/diagnóstico , Arteria Pulmonar/fisiología , Venas Cavas/fisiología , Adolescente , Análisis de Varianza , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Hemodinámica , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Lactante , Masculino , Complicaciones Posoperatorias/fisiopatología , Programas Informáticos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Acute vasoreactivity testing (VT) is considered mandatory in the diagnostic work-up of patients with pulmonary arterial hypertension (PAH). We studied the relation between the acute absolute arterial vasodilatation and the severity of vascular remodeling estimated by intravascular ultrasound (IVUS) in patients with idiopathic PAH. METHODS: Simultaneous right heart catheterization and IVUS of the pulmonary artery (PA) were performed both in basal conditions and during short-term intravenous epoprostenol infusion in nineteen idiopathic PAH patients. Pulmonary vascular resistance (PVRi) and capacitance indexes (stroke volume/pulse pressure, Cp), were calculated. Local pulsatility was estimated by IVUS (IVUSp) (systolic-diastolic lumen area/diastolic lumen area×100; sA-dA/dA) and PA stiffness was assessed by the elastic modulus (E: pulse pressure/IVUSp). RESULTS: Epoprostenol infusion (11±2ng/kg/min) determined a real vasodilatation (increment of dA>10%) in six patients. This vasodilation group presented on average significantly higher cardiac index, stroke volume index and Cp, and lower PVRi and IVUSp (P<0.05), with a lower E (P=0.08). Three patients were responders according to the actual criteria, but only one showed a real vasodilator response. Baseline E below the median value (≤190mm Hg) was able to differentiate patients with an acute vasodilator response (sensibility 83%, specificity 73%, area under ROC 0.81; P<0.05). Neither E nor vasodilator response is correlated with delta mean PA pressure and PVRi. CONCLUSIONS: Patients with higher IVUSp and lesser E displayed an absolute PA vasodilation during VT with epoprostenol. The patients with a positive VT according to actual criteria do not necessarily have a real vasodilatation on intravascular ultrasound.
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Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/fisiología , Rigidez Vascular/fisiología , Vasodilatación/fisiología , Adulto , Anciano , Cateterismo Cardíaco/métodos , Epoprostenol/farmacología , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/efectos de los fármacos , Rigidez Vascular/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: The aim of this study was to examine the effects of controlled hemorrhage and shock on oxygenation and ventilation using needle cricothyroidotomy and jet ventilation in an animal model. METHODS: Twenty-four male pigs were randomly allocated into 4 groups: SHOCK (animals in hemorrhagic shock only), CRICH (animals that underwent needle cricothyroidotomy only), SHOCK+CRICH (animals in hemorrhagic shock + needle cricothyroidotomy), and SHAM (anesthetized animals submitted to surgical preparation only). All animals were surgically prepared and were observed for a period of 40 minutes (T0 - T40). Hemodynamic and blood gas variables were compared using analysis of variance and Bonferroni post hoc testing at a level of significance of 95%. RESULTS: CRICH and SHOCK+CRICH developed respiratory acidosis, with a progressive decrease of arterial pH after T20, and they presented a significant increase of PaCO(2) levels after T10, when compared with SHAM and SHOCK (P < .001). When SHOCK+CRICH was compared with CRICH, it presented a larger increase of PaCO(2) after T10 (P = .036) and an even more significant increase after T20 (P = .009). CONCLUSION: Hemorrhagic shock anticipated and intensified the retention of carbon dioxide and respiratory acidosis during manual jet ventilation through needle cricothyroidotomy in comparison with animals with jet ventilation but without shock. The results found in this work should be considered in future protocols for the assistance of victims of trauma in prehospital settings.