RESUMO
High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.
Assuntos
Doença da Altitude/fisiopatologia , Endotélio Vascular/embriologia , Endotélio Vascular/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Edema Pulmonar/fisiopatologia , Doença da Altitude/complicações , Doença da Altitude/embriologia , Desenvolvimento Fetal , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/embriologia , Óxido Nítrico/biossíntese , Óxido Nítrico/deficiência , Estresse Oxidativo , Edema Pulmonar/embriologia , Edema Pulmonar/etiologiaRESUMO
La altura constituye un fascinante laboratorio natural para la investigación médica. Si bien al principio el objetivo de la investigación en la altura fue la comprensión de los mecanismos de adaptación del organismo a la hipoxia y la búsqueda de tratamientos para las enfermedades relacionadas con la altura, durante la última década el alcance de esta investigación se ha ampliado considerablemente. Dos importantes observaciones han generado las bases para el crecimiento del alcance científico de la investigación en la altura. Primero, el hecho de que el edema pulmonar agudo de la altura constituye un modelo único para estudiar los mecanismos fundamentales de la hipertensión pulmonar y el edema pulmonar en humanos. Segundo, que la hipoxia ambiental asociada con la exposición a la altura facilita la detección de disfunción vascular pulmonar y sistémica en un estadio precoz. Aquí revisaremos los estudios que, capitalizando estas observaciones, han llevado a la descripción de nuevos mecanismos subyacentes del edema pulmonar y de la hipertensión pulmonar, y a la primera demostración directa de la existencia de una programación fetal sobre la disfunción vascular en humanos.
High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.
Assuntos
Humanos , Doença da Altitude/fisiopatologia , Endotélio Vascular/embriologia , Endotélio Vascular/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Edema Pulmonar/fisiopatologia , Doença da Altitude/complicações , Doença da Altitude/embriologia , Desenvolvimento Fetal , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/embriologia , Óxido Nítrico/biossíntese , Óxido Nítrico/deficiência , Estresse Oxidativo , Edema Pulmonar/embriologia , Edema Pulmonar/etiologiaRESUMO
La altura constituye un fascinante laboratorio natural para la investigación médica. Si bien al principio el objetivo de la investigación en la altura fue la comprensión de los mecanismos de adaptación del organismo a la hipoxia y la búsqueda de tratamientos para las enfermedades relacionadas con la altura, durante la última década el alcance de esta investigación se ha ampliado considerablemente. Dos importantes observaciones han generado las bases para el crecimiento del alcance científico de la investigación en la altura. Primero, el hecho de que el edema pulmonar agudo de la altura constituye un modelo único para estudiar los mecanismos fundamentales de la hipertensión pulmonar y el edema pulmonar en humanos. Segundo, que la hipoxia ambiental asociada con la exposición a la altura facilita la detección de disfunción vascular pulmonar y sistémica en un estadio precoz. Aquí revisaremos los estudios que, capitalizando estas observaciones, han llevado a la descripción de nuevos mecanismos subyacentes del edema pulmonar y de la hipertensión pulmonar, y a la primera demostración directa de la existencia de una programación fetal sobre la disfunción vascular en humanos.(AU)
High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.(AU)
RESUMO
La altura constituye un fascinante laboratorio natural para la investigación médica. Si bien al principio el objetivo de la investigación en la altura fue la comprensión de los mecanismos de adaptación del organismo a la hipoxia y la búsqueda de tratamientos para las enfermedades relacionadas con la altura, durante la última década el alcance de esta investigación se ha ampliado considerablemente. Dos importantes observaciones han generado las bases para el crecimiento del alcance científico de la investigación en la altura. Primero, el hecho de que el edema pulmonar agudo de la altura constituye un modelo único para estudiar los mecanismos fundamentales de la hipertensión pulmonar y el edema pulmonar en humanos. Segundo, que la hipoxia ambiental asociada con la exposición a la altura facilita la detección de disfunción vascular pulmonar y sistémica en un estadio precoz. Aquí revisaremos los estudios que, capitalizando estas observaciones, han llevado a la descripción de nuevos mecanismos subyacentes del edema pulmonar y de la hipertensión pulmonar, y a la primera demostración directa de la existencia de una programación fetal sobre la disfunción vascular en humanos.(AU)
High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.(AU)
RESUMO
BACKGROUND: Chronic mountain sickness (CMS) is an important public health problem and is characterized by exaggerated hypoxemia, erythrocytosis, and pulmonary hypertension. While pulmonary hypertension is a leading cause of morbidity and mortality in patients with CMS, it is relatively mild and its underlying mechanisms are not known. We speculated that during mild exercise associated with daily activities, pulmonary hypertension in CMS is much more pronounced. METHODS: We estimated pulmonary artery pressure by using echocardiography at rest and during mild bicycle exercise at 50 W in 30 male patients with CMS and 32 age-matched, healthy control subjects who were born and living at an altitude of 3,600 m. RESULTS: The modest, albeit significant difference of the systolic right-ventricular-to-right-atrial pressure gradient between patients with CMS and controls at rest (30.3 +/- 8.0 vs 25.4 +/- 4.5 mm Hg, P 5 .002) became more than three times larger during mild bicycle exercise (56.4 +/- 19.0 vs 39.8 +/- 8.0 mm Hg, P < .001). CONCLUSIONS: Measurements of pulmonary artery pressure at rest greatly underestimate pulmonary artery pressure during daily activity in patients with CMS. The marked pulmonary hypertension during mild exercise associated with daily activity may explain why this problem is a leading cause of morbidity and mortality in patients with CMS.
Assuntos
Doença da Altitude/complicações , Teste de Esforço/métodos , Exercício Físico/fisiologia , Hipertensão Pulmonar/etiologia , Pressão Propulsora Pulmonar/fisiologia , Doença da Altitude/epidemiologia , Doença da Altitude/fisiopatologia , Bolívia/epidemiologia , Doença Crônica , Teste de Esforço/efeitos adversos , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Prognóstico , Taxa de Sobrevida/tendênciasRESUMO
A realização de Consultorias em Ética Clínica tem sido reduzida, muitas vezes, a uma simples aplicação de um método de análise de casos baseados em princípios. A consultoria seria reduzida a uma simples avaliação de um conflito entre princípios. A proposta de uma abordagem baseada em uma Deliberação de Caso Moral pode ser uma alternativa importante, onde o consultor atua como facilitador e não tomando decisões que cabem aos profissionais de saúde.
Clinical Ethics Consultancy, often, has been reduced as a simple method of case analysis based on principles. The consultancy would be reduced to a simple evaluation of a conflict between principles. The proposed approach based on a Moral Case Deliberation could be an important alternative, where the consultant acts as a facilitator and not as a decision maker.
Assuntos
Humanos , Consultoria Ética/ética , Consultoria Ética/história , Consultoria Ética/normas , Consultoria Ética/tendências , Ética Clínica , Bioética/tendências , Ética Baseada em PrincípiosRESUMO
Obesity, insulin resistance and associated cardiovascular complications are reaching epidemic proportions worldwide and represent a major public health problem. Over the past decade, evidence has accumulated indicating that insulin administration, in addition to its metabolic effects, also has important cardiovascular actions. The sympathetic nervous system and the L-arginine-nitric oxide pathway are the central players in the mediation of insulin's cardiovascular actions. Based on recent animal and human research, we demonstrate that both defective and augmented NO synthesis represent a central defect triggering many of the metabolic, vascular and sympathetic abnormalities characteristic of insulin-resistant states. These observations provide the rationale for the use of pharmaceutical drugs releasing small and physiological amounts of NO and/or inhibitors of NO overproduction as a future treatment for insulin resistance and associated comorbidities.
Assuntos
Hipoglicemiantes/farmacologia , Resistência à Insulina/fisiologia , Insulina/farmacologia , Óxido Nítrico/biossíntese , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Disponibilidade Biológica , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Homeostase , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Óxido Nítrico/deficiência , Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Sistema Nervoso Simpático/fisiopatologiaRESUMO
Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.
Assuntos
Altitude , Expiração/fisiologia , Hipertensão Pulmonar/etnologia , Óxido Nítrico/metabolismo , Pressão Propulsora Pulmonar/fisiologia , Adaptação Fisiológica , Adolescente , Ar/análise , Bolívia/epidemiologia , Criança , Pré-Escolar , Europa (Continente)/etnologia , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Incidência , Lactente , Masculino , Fatores de RiscoRESUMO
La incidencia de la obesidad y de la resistencia a la insulina con sus complicaciones asociadas, como la hipertensión arterial y el aumento de la morbi-mortalidad cardiovascular, alcanzan hoy en día proporciones epidémicas y representan un problema mayor de salud pública. En los últimos años se ha demostrado que la administración de insulina, además de sus efectos metabólicos, posee efectos cardiovasculares importantes. El sistema nervioso simpático y el sistema L-arginina - óxido nítrico son los mediadores centrales de estas acciones cardiovasculares de la insulina. Mostramos, gracias a estudios realizados en animales y en humanos, que no sólo un déficit de la síntesis del óxido nítrico (NO), sino también un aumento exagerado en su producción representan un defecto subyacente central de las anomalías metabólicas, cardiovasculares y del sistema nervioso simpático que caracterizan a la insulino resistencia. Mostramos cómo estos resultados establecen el fundamento científico para la utilización de sustancias farmacológicas capaces de liberar de manera prolongada cantidades fisiológicas de NO o de inhibidores de su sobreproducción como futuros tratamientos para la resistencia a la insulina y sus complicaciones asociadas.
Obesity, insulin resistance and associated cardiovascular complications are reaching epidemic proportions worldwide and represent a major public health problem. Over the past decade, evidence has accumulated indicating that insulin administration, in addition to its metabolic effects, also has important cardiovascular actions. The sympathetic nervous system and the L-arginine-nitric oxide pathway are the central players in the mediation of insulin's cardiovascular actions. Based on recent animal and human research, we demonstrate that both defective and augmented NO synthesis represent a central defect triggering many of the metabolic, vascular and sympathetic abnormalities characteristic of insulin-resistant states. These observations provide the rationale for the use of pharmaceutical drugs releasing small and physiological amounts of NO and/or inhibitors of NO overproduction as a future treatment for insulin resistance and associated comorbidities.
Assuntos
Animais , Humanos , Ratos , Hipoglicemiantes/farmacologia , Resistência à Insulina/fisiologia , Insulina/farmacologia , Óxido Nítrico/biossíntese , Sistema Nervoso Simpático/efeitos dos fármacos , Disponibilidade Biológica , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Homeostase , Hipertensão/etiologia , Hipertensão/fisiopatologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/deficiência , Óxido Nítrico/farmacologia , Sistema Nervoso Simpático/fisiopatologiaRESUMO
There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.
Assuntos
Aclimatação/fisiologia , Altitude , Pressão Sanguínea/fisiologia , Monitoramento Ambiental , Indígenas Sul-Americanos , População Branca , Adulto , Bolívia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etnologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Óxido Nítrico/metabolismo , Oximetria , Artéria Pulmonar/fisiologia , Fatores de RiscoRESUMO
High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, it has become clear that the results of high-altitude research may have important implications not only for the understanding of diseases in the millions of people living permanently at high altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general.
Assuntos
Doença da Altitude/complicações , Hipertensão Pulmonar/complicações , Circulação Pulmonar , Edema Pulmonar/etiologia , Sistema Nervoso Simpático , Doença da Altitude/tratamento farmacológico , Doença da Altitude/fisiopatologia , Disponibilidade Biológica , Transporte Biológico/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Canais Epiteliais de Sódio/fisiologia , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Óxido Nítrico/biossíntese , Alvéolos Pulmonares/efeitos dos fármacos , Circulação Pulmonar/fisiologia , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/fisiopatologia , Sódio/farmacocinética , Sódio/uso terapêutico , Sistema Nervoso Simpático/fisiopatologiaRESUMO
La altura, fascinante laboratorio natural de investigación médica, provee resultados con importantes implicancias para la comprensión de enfermedades que afectan a millones de personas que viven en ella, asi como para el tratamiento de enfermedades ligadas a la hipoxemia en pacientes que viven en baja altitud. El edema pulmonar de altura (EPA) es una entidad que pone en peligro la vida y que ocurre en sujetos predispuestos pero sanos. Esto permite estudiar los mecanismos subyacentes del edema pulmonar en humanos, sin la presencia de factores que presten a la confusión como enfermedades concomitantes. El EPA resulta de la conjunción de dos defectos mayores: acumulación de líquido en el espacio alveolar debido a una hipertensión pulmonar hipóxica exagerada, y alteración en la eliminación del mismo por un defecto en el transporte transepitelial alveolar de sodio. En esta revisión, describimos brevemente las características clínicas y revisaremos este novedoso concepto. Proveemos evidencia experimental de como la síntesis alterada de óxido nítrico y/o la disminución de su biodisponibilidad representan el defecto central que predispone a la vasoconstricción pulmonar hipóxica exagerada y a la acumulación de líquido en el espacio alveolar. Mostramos que la hipertensión pulmonar hipóxica exagerada, per se, no es suficiente para producir un EPA, y que una alteración en la eliminación del fluido del espacio alveolar representa un segundo mecanismo fisiopatológico importante. Finalmente, describimos cómo los nuevos aportes obtenidos de los estudios del EPA pueden ser trasladados al manejo de otros estados patológicos ligados a la hipoxemia.
High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, it has become clear that the results of high-altitude research may have important implications not only for the understanding of diseases in the millions of people living permanently at high altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general.
Assuntos
Humanos , Doença da Altitude/fisiopatologia , Hipertensão Pulmonar/complicações , Circulação Pulmonar , Edema Pulmonar/etiologia , Sistema Nervoso Simpático , Doença da Altitude/complicações , Doença da Altitude/tratamento farmacológico , Disponibilidade Biológica , Transporte Biológico/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Canais Epiteliais de Sódio/fisiologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Óxido Nítrico/biossíntese , Óxido Nítrico/farmacocinética , Alvéolos Pulmonares/efeitos dos fármacos , Circulação Pulmonar/fisiologia , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/fisiopatologia , Sódio/farmacocinética , Sódio/uso terapêutico , Sistema Nervoso Simpático/fisiopatologiaRESUMO
La altura, fascinante laboratorio natural de investigación médica, provee resultados con importantes implicancias para la comprensión de enfermedades que afectan a millones de personas que viven en ella, asi como para el tratamiento de enfermedades ligadas a la hipoxemia en pacientes que viven en baja altitud. El edema pulmonar de altura (EPA) es una entidad que pone en peligro la vida y que ocurre en sujetos predispuestos pero sanos. Esto permite estudiar los mecanismos subyacentes del edema pulmonar en humanos, sin la presencia de factores que presten a la confusión como enfermedades concomitantes. El EPA resulta de la conjunción de dos defectos mayores: acumulación de líquido en el espacio alveolar debido a una hipertensión pulmonar hipóxica exagerada, y alteración en la eliminación del mismo por un defecto en el transporte transepitelial alveolar de sodio. En esta revisión, describimos brevemente las características clínicas y revisaremos este novedoso concepto. Proveemos evidencia experimental de como la síntesis alterada de óxido nítrico y/o la disminución de su biodisponibilidad representan el defecto central que predispone a la vasoconstricción pulmonar hipóxica exagerada y a la acumulación de líquido en el espacio alveolar. Mostramos que la hipertensión pulmonar hipóxica exagerada, per se, no es suficiente para producir un EPA, y que una alteración en la eliminación del fluido del espacio alveolar representa un segundo mecanismo fisiopatológico importante. Finalmente, describimos cómo los nuevos aportes obtenidos de los estudios del EPA pueden ser trasladados al manejo de otros estados patológicos ligados a la hipoxemia. (AU)
High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, it has become clear that the results of high-altitude research may have important implications not only for the understanding of diseases in the millions of people living permanently at high altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general. (AU)
Assuntos
Humanos , Doença da Altitude/fisiopatologia , Edema Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Sistema Nervoso Simpático , Circulação Pulmonar , Doença da Altitude/complicações , Doença da Altitude/tratamento farmacológico , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/fisiopatologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Transporte Biológico/fisiologia , Canais Epiteliais de Sódio/fisiologia , Alvéolos Pulmonares/efeitos dos fármacos , Sódio/farmacocinética , Sódio/uso terapêutico , Óxido Nítrico/biossíntese , Óxido Nítrico/farmacocinética , Sistema Nervoso Simpático/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Circulação Pulmonar/fisiologia , Disponibilidade BiológicaRESUMO
The prevalence of hypertension among adults of both sexes was assessed as part of a primary medical attention program in an Indian Wichi-Chorote community in Santa Victoria Este, province of Salta, Argentina. Arterial blood pressure was measured after a five minutes rest in a sitting position in adults (over 18 years old) of both sexes with a calibrated sphygmomanometer. A total of 522 adults (318 women and 204 men) were evaluated with median age of 43.5 +/- 16.3. The mean systolic blood pressure (SBP) was 125.2 +/- 22.7 mm Hg, and the mean dyastolic blood pressure (DBP) was 76.3 +/- 12.8 mm Hg. Thirty five percent of the people evaluated had normal pressure values (SBP<80 and DBP<120), 37% prehypertensive (SBP 120-139 or DBP 80-89) and 28% hypertensive (SBP > or = 140 or DBP > or = 90). Thirty one percent of the men (mean age: 43.93 +/- 17.11, mean SBP: 126.81 +/- 22.61 and mean DBP: 77.80 +/- 13.33) and 27% of the women studied (mean age: 42.93 +/- 16.3, mean SBP: 124.92 +/- 24.02 and mean DBP: 75.28 +/- 12.57) were hypertense. Fifty nine percent of the people over 65 years of age (n:58) (mean age: 73.15 +/- 6.36, mean SBP: 144.81 +/- 28.72 and mean DBP: 79.68 +/- 13.17) had blood pressure values in the hypertense range. The prevalence of hypertension in the evaluated rural population, suffering extreme demographic and sanitary conditions, is similar to that reported for urbanized societies in the USA but lower than the one reported for other rural areas of our country.
Assuntos
Hipertensão/epidemiologia , Indígenas Sul-Americanos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores SocioeconômicosRESUMO
The prevalence of hypertension among adults of both sexes was assessed as part of a primary medical attention program in an Indian Wichi-Chorote community in Santa Victoria Este, province of Salta, Argentina. Arterial blood pressure was measured after a five minutes rest in a sitting position in adults (over 18 years old) of both sexes with a calibrated sphygmomanometer. A total of 522 adults (318 women and 204 men) were evaluated with median age of 43.5 +/- 16.3. The mean systolic blood pressure (SBP) was 125.2 +/- 22.7 mm Hg, and the mean dyastolic blood pressure (DBP) was 76.3 +/- 12.8 mm Hg. Thirty five percent of the people evaluated had normal pressure values (SBP<80 and DBP<120), 37
prehypertensive (SBP 120-139 or DBP 80-89) and 28
hypertensive (SBP > or = 140 or DBP > or = 90). Thirty one percent of the men (mean age: 43.93 +/- 17.11, mean SBP: 126.81 +/- 22.61 and mean DBP: 77.80 +/- 13.33) and 27
of the women studied (mean age: 42.93 +/- 16.3, mean SBP: 124.92 +/- 24.02 and mean DBP: 75.28 +/- 12.57) were hypertense. Fifty nine percent of the people over 65 years of age (n:58) (mean age: 73.15 +/- 6.36, mean SBP: 144.81 +/- 28.72 and mean DBP: 79.68 +/- 13.17) had blood pressure values in the hypertense range. The prevalence of hypertension in the evaluated rural population, suffering extreme demographic and sanitary conditions, is similar to that reported for urbanized societies in the USA but lower than the one reported for other rural areas of our country.