Fisiología respiratoria. Neumología de altura: saturación de oxígeno, edema pulmonar y pruebas de función pulmonar / Respiratory physiology - High -altitude pneumology: oxygen saturation, pulmonary edema and pulmonary function tests

En las alturas, sobre todo a 2500 metros sobre el nivel del mar, la cantidad absoluta de oxígeno va decreciendo y por lo tanto la cantidad disponible para el intercambio gaseoso disminuye, produciéndose una vasoconstricción hipóxica pulmonar (VHP). La VHP asociada a la hipoxia hipobárica de la altura produce un aumento de la presión pulmonar que es mayor en los lactantes y a mayores alturas. No hay valores únicos de saturación de oxígeno (SatO2) en la altura, porque ésta va disminuyendo según el mayor nivel de altura, aumenta con la edad, y la brecha entre la vigilia y sueño es grande (sobre todo en los primeros meses de vida). El 25% de los niños sanos que viven en altura tienen valores de SatO2 significativamente menores que el 75% restante. Los valores normales de los índices de apnea/hipopnea son distintos a los de nivel del mar. El edema pulmonar de las alturas es una patología frecuente, que se produce por un incremento desproporcionado en la VHP reflejando una hiperactividad del lecho vascular pulmonar ante la exposición aguda a la hipoxia hipobárica. Tiene cuatro fenotipos, es infrecuente en menores de 5 años y rara vez es mortal, la sospecha clínica y el manejo oportuno con oxigeno es la clave. Finalmente, en la altura los valores normales de la función pulmonar de la espirometría, oscilometría de impulso y capacidad de difusión son distintos que a nivel del mar.

At high altitude, especially > 2,500 meters above sea level, the absolute amount of oxygen decreases and therefore the amount available for gas exchange decreases, producing hypoxic pulmonary vasoconstriction (VHP). VHP associated with high-altitude hypobaric hypoxia produces an increase in pulmonary pressure that is greater in infants and at higher altitudes. There are no single values of oxygen saturation (SatO2) at altitude, because it decreases with the highest level of altitude, increases with age, and the gap between wakefulness and sleep is large (especially in the first months of life). Around 25% of healthy children living at altitude have SatO2 values significantly lower than the remaining 75%. The normal values of the apnea/hypopnea indices are different from those at sea level. High altitude pulmonary edema is a frequent pathology that is produced by a disproportionate increase in VHP reflecting hyperactivity of the pulmonary vascular bed in the face of acute exposure to hypobaric hypoxia, it has four phenotypes, it is uncommon in children under 5 years of age, and it is rarely fatal, the clinical suspicion and timely management with oxygen is the key. Finally, at high altitude, the normal values of lung function from spirometry, impulse oscillometry, and diffusing capacity are different from those at sea level.

"Tiger stripes" sign in acute coronary syndrome.

The incidence of mitral regurgitation in acute myocardial syndromes is variable. Echocardiographic evaluation is fundamental in making a proper diagnosis of mechanical complications and to offer timely treatment. We present a case of a 64-year-old male who was admitted to the ER in acute pulmonary edema. The electrocardiogram showed negative ST-segment deviation from V4-V6, positive ST-segment deviation in aVR. Multivessel disease with severe mitral regurgitation was seen in catheterization. A transthoracic echocardiogram revealed important mitral regurgitation showing the "tiger stripes" sign, seen in the presence of intracardial oscillating structures, in this case, suspected papillary muscle rupture. Echocardiographic evaluation is necessary in every case of myocardial infarction who present with new-onset mitral regurgitation. Treatment is complex and must be determined with an interdisciplinary group.

Tiger stripes sign in acute coronary syndrome / Signo manchas de tigre en síndrome coronario agudo

Abstract The incidence of mitral regurgitation in acute myocardial syndromes is variable. Echocardiographic evaluation is fundamental in making a proper diagnosis of mechanical complications and to offer timely treatment. We present a case of a 64-year-old male who was admitted to the ER in acute pulmonary edema. The electrocardiogram showed negative ST-segment deviation from V4-V6, positive ST-segment deviation in aVR. Multivessel disease with severe mitral regurgitation was seen in catheterization. A transthoracic echocardiogram revealed important mitral regurgitation showing the "tiger stripes" sign, seen in the presence of intracardial oscillating structures, in this case, suspected papillary muscle rupture. Echocardiographic evaluation is necessary in every case of myocardial infarction who present with new-onset mitral regurgitation. Treatment is complex and must be determined with an interdisciplinary group.

Personalized pharmacological therapy for ARDS: a light at the end of the tunnel.

Introduction: Pharmacotherapy for the acute respiratory distress syndrome (ARDS) has been tested in preclinical and clinical studies. However, to date, no pharmacological interventions have proven effective. This may be attributed to lack of proper identification of different ARDS phenotypes.Areas covered: We designed inclusive search strings and searched four bibliographic databases (Cochrane Database of Systematic Reviews, PubMed, Web of Science, and clinicaltrials.gov) to identify relevant research. Search results were mainly restricted to papers published from 2009 through 2019. ARDS is a heterogeneous syndrome, and its different phenotypes - defined according to clinical, radiological, and biological parameters - may affect response to therapy. The most promising pharmacological approaches to date have been based on ARDS pathophysiology. They focus on reducing inflammation and pulmonary edema, promoting selective vasodilation, and repairing alveolar epithelial and endothelial cells.Expert opinion: Pharmacotherapeutic approaches targeting ARDS pathophysiology have failed to exert beneficial effects. Personalized medicine targeting the different ARDS phenotypes has emerged as an option to improve survival. Identification of specific ARDS patient phenotypes that respond to specific therapies seems to be the most important challenge for the next decade. Additional research is warranted before personalized medicine approaches can be applied at bedside for ARDS patients.

Effects of Obesity on Pulmonary Inflammation and Remodeling in Experimental Moderate Acute Lung Injury.

Obese patients are at higher risk of developing acute respiratory distress syndrome (ARDS); however, their survival rates are also higher compared to those of similarly ill non-obese patients. We hypothesized that obesity would not only prevent lung inflammation, but also reduce remodeling in moderate endotoxin-induced acute lung injury (ALI). Obesity was induced by early postnatal overfeeding in Wistar rats in which the litter size was reduced to 3 pups/litter (Obese, n = 18); Control animals (n = 18) were obtained from unculled litters. On postnatal day 150, Control, and Obese animals randomly received E. coli lipopolysaccharide (ALI) or saline (SAL) intratracheally. After 24 h, echocardiography, lung function and morphometry, and biological markers in lung tissue were evaluated. Additionally, mediator expression in neutrophils and macrophages obtained from blood and bronchoalveolar lavage fluid (BALF) was analyzed. Compared to Control-SAL animals, Control-ALI rats showed no changes in echocardiographic parameters, increased lung elastance and resistance, higher monocyte phagocytic capacity, collagen fiber content, myeloperoxidase (MPO) activity, and levels of interleukin (IL-6), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, and type III (PCIII), and I (PCI) procollagen in lung tissue, as well as increased expressions of TNF-α and monocyte chemoattractant protein (MCP)-1 in blood and BALF neutrophils. Monocyte (blood) and macrophage (adipose tissue) phagocytic capacities were lower in Obese-ALI compared to Control-ALI animals, and Obese animals exhibited reduced neutrophil migration compared to Control. Obese-ALI animals, compared to Obese-SAL, exhibited increased interventricular septum thickness (p = 0.003) and posterior wall thickness (p = 0.003) and decreased pulmonary acceleration time to pulmonary ejection time ratio (p = 0.005); no changes in lung mechanics, IL-6, TNF-α, TGF-ß, PCIII, and PCI in lung tissue; increased IL-10 levels in lung homogenate (p = 0.007); reduced MCP-1 expression in blood neutrophils (p = 0.009); decreased TNF-α expression in blood (p = 0.02) and BALF (p = 0.008) neutrophils; and increased IL-10 expression in monocytes (p = 0.004). In conclusion, after endotoxin challenge, obese rats showed less deterioration of lung function, secondary to anti-inflammatory and anti-fibrotic effects, as well as changes in neutrophil and monocyte/macrophage phenotype in blood and BALF compared to Control rats.

[Postictal pulmonary oedema: a review of the literature]. / Edema pulmonar postictal: revision de la bibliografia.

INTRODUCTION: Postictal neurogenic pulmonary oedema is an infrequent condition of varying severity, probably related to sudden unexpected death in epilepsy (SUDEP). It is more frequent in patients with generalised tonic-clonic seizures of long duration or with status epilepticus. AIM: Based on a review of the literature, the aim is to describe the clinical characteristics, pathophysiology, radiological findings, treatment and prognosis of patients with postictal pulmonary oedema. DEVELOPMENT: A search of the literature was performed in the PubMed, Embase, Cochrane Database of Systematic Reviews and BVS databases using a combination of free terms. The limits of the search applied were: papers published between 1 January 2000 and 26 April 2018, and papers for which the abstract was available. Altogether 23 papers were found, most of which were clinical cases, and used to extract the information needed to carry out the review. CONCLUSIONS: In postictal pulmonary oedema, generalised tonic-clonic seizures are the most frequently reported type. The most common clinical manifestations were dyspnoea and tachycardia appearing within a few minutes after the seizure. Among the paraclinical findings the most frequent was leukocytosis. In general terms, a good prognosis was found in most cases, with improvement of the oedema within a period of between 12 and 96 hours. Only two of the 21 patients reported died. In addition, in a clinical pathology study in patients with SUDEP, pulmonary oedema appeared in most cases.

TITLE: Edema pulmonar postictal: revision de la bibliografia.Introduccion. El edema pulmonar neurogeno postictal es una patologia poco frecuente con gravedad variable, probablemente en relacion con la muerte subita asociada a la epilepsia (SUDEP). La frecuencia es mayor en pacientes con crisis tonicoclonicas generalizadas de larga duracion o con estado epileptico. Objetivo. Por medio de una revision de la bibliografia se pretende describir las caracteristicas clinicas, la fisiopatologia, los hallazgos radiologicos, el tratamiento y el pronostico de los pacientes con edema pulmonar postictal. Desarrollo. Se realizo una busqueda de la bibliografia en las bases de datos PubMed, Embase, Cochrane y BVS empleando una combinacion de terminos libres. Se aplicaron como limites de busqueda: articulos publicados desde el 1 de enero de 2000 hasta el 26 de abril de 2018 y articulos que contaran con el resumen disponible. En total se revisaron 23 articulos, en su mayoria casos clinicos, de los cuales se obtuvo la informacion para desarrollar la revision. Conclusiones. En el edema pulmonar postictal, el tipo de crisis mas frecuentemente comunicada es la tonicoclonica generalizada. Las manifestaciones clinicas mas habituales fueron disnea y taquicardia de aparicion en los minutos posteriores a la crisis. En los paraclinicos, el hallazgo mas frecuente fue leucocitosis. En general se encontro un buen pronostico en la mayoria de los casos, con mejoria del edema entre las 12 y las 96 horas. Unicamente dos de los 21 pacientes comunicados fallecieron. Ademas, en un estudio clinico de patologia en pacientes con SUDEP, el edema pulmonar aparecio en la mayoria de los casos.

New determinants for casual peripheral mechanism of neurogenic lung edema in subarachnoid hemorrhage due to ischemic degeneration of vagal nerve, kidney and lung circuitry. Experimental study

Purpose:To evaluate whether there is a relationship between renal artery vasospasm related low glomerular density or degeneration and neurogenic lung edema (NLE) following subarachnoid hemorrhage.Methods:This study was conducted on 26 rabbits. A control group was formed of five animals, a SHAM group of 5 to which saline and a study group (n=16) injected with homologous blood into the sylvian cisterna. Numbers of degenerated axons of renal branches of vagal nerves, atrophic glomerulus numbers and NLE scores were recorded.Results:Important vagal degeneration, severe renal artery vasospasm, intrarenal hemorrhage and glomerular atrophy observed in high score NLE detected animals. The mean degenerated axon density of vagal nerves (n/mm2), atrophic glomerulus density (n/mm3) and NLE scores of control, SHAM and study groups were estimated as 2.40±1.82, 2.20±1.30, 1.80±1.10, 8.00±2.24, 8.80±2.39, 4.40±1.14 and 154.38±13.61, 34.69±2.68 and 12.19±1.97 consecutively. Degenerated vagal axon, atrophic glomerulus and NLE scores are higher in study group than other groups and the differences are statistically meaningful (p<0.001).Conclusion:Vagal complex degeneration based glomerular atrophy have important roles on NLE following SAH which has not been extensively mentioned in the literature.(AU)

Functional capacity in a rat model of heart failure: impact of myocardial infarct size.

NEW FINDINGS: What is the central question of this study? To the best of our knowledge, no studies have evaluated oxygen uptake, carbon dioxide production and exercise tolerance in rats that have undergone myocardial infarction classified by myocardial infarct (MI) size. What is the main finding and its importance? Oxygen uptake and exercise intolerance are MI size dependent, and classification based on MI size can distinguish rats with functional capacity impairment. Rats with a large MI (>40% of the left ventricle) might provide a good model for the testing of new therapies that have the potential to modify the variables of functional capacity. Oxygen uptake (V̇O2) and exercise tolerance in rats classified by myocardial infarct (MI) size are underexplored. The aim of this study was to evaluate V̇O2, carbon dioxide production (V̇CO2) and exercise tolerance in rats that had undergone myocardial infarction. Fourteen weeks after myocardial infarction or sham surgery, rats underwent an integrated approach to evaluation of left ventricular function and V̇O2/V̇O2V̇CO2V̇CO2, exercise tolerance and skeletal muscle weight. Based on determination of MI size, rats were assigned to sham-operated controls (Sham, n = 12), small myocardial infarction (SMI, n = 8) and large myocardial infarction (LMI, n = 5) groups. The LMI rats showed lower systolic (ejection fraction and fractional shortening) and diastolic (E/A ratio) left ventricular function compared with SMI. Maximal V̇O2 (∼24%, P < 0.05), V̇O2 reserve (∼30%, P < 0.05), time to exhaustion (∼36%, P < 0.05) and maximal velocity (∼30%, P < 0.05) were lower in LMI compared with sham-operated control animals, with no difference between SMI rats and sham-operated controls. Maximal V̇CO2 and respiratory exchange ratio showed no significant difference between MI rats and sham-operated control rats. The LMI rats demonstrated lower gastrocnemius weight (∼12%, P < 0.05) and soleus weight (∼19%, P = 0.07) compared with sham-operated control rats. Significant correlations between MI size, left ventricular end-diastolic pressure, right ventricle hypertrophy, pulmonary congestion, ejection fraction and fractional shortening with maximal V̇O2 and distance run were observed. Oxygen uptake and exercise intolerance are MI size dependent.

Edema pulmonar de reexpansão na doença pleural / Re-expansion pulmonary edema in pleural disease

O edema pulmonar de reexpansão é uma condição clínica rara, porém frequentemente letal. É uma complicação secundária à rápida reexpansão do pulmão colapsado em consequência a um pneumotórax ou derrame pleural de grande volume. São de fundamental importância para sua prevenção, o conhecimento da etiopatogenia e a execução de técnica adequada na drenagem pleural tubular e na toracocentese. A sua patogênese é multifatorial. O esvaziamento lento da cavidade pleural, a monitorização da oximetria e administração de oxigênio são necessários para prevenção e tratamento. AU

The reexpansion pulmonary edema (RPE) is a rare clinical condition, but often lethal. It is a secondary complication to the rapid re-expansion of the lung collapsed as a result of a pneumothorax or pleural effusion of large volume. The fundamental importance for prevention are knowledge of the pathogenesis and executing proper technique on pleural drainage and thoracentesis. Its pathogenesis is multifactorial. Its prevention is still based on slow pleuralemptying procedures, without standards to avoid RPEevolution. The oximetry monitoring and administration of oxygen are needed for treatment. AU

Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation.

Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation.

Experimental lung injury promotes alterations in energy metabolism and respiratory mechanics in the lungs of rats: prevention by exercise.

In the present study we investigated the effects of lung injury on energy metabolism (succinate dehydrogenase, complex II, cytochrome c oxidase, and ATP levels), respiratory mechanics (dynamic and static compliance, elastance and respiratory system resistance) in the lungs of rats, as well as on phospholipids in bronchoalveolar lavage fluid. The protective effect of physical exercise on the alterations caused by lung injury, including lung edema was also evaluated. Wistar rats were submitted to 2 months of physical exercise. After this period the lung injury was induced by intratracheal instillation of lipopolysaccharide. Adult Wistar rats were submitted to 2 months of physical exercise and after this period the lung injury was induced by intratracheal instillation of lipopolysaccharide in dose 100 µg/100 g body weight. The sham group received isotonic saline instillation. Twelve hours after the injury was performed the respiratory mechanical and after the rats were decapitated and samples were collected. The rats subjected to lung injury presented a decrease in activities of the enzymes of the electron transport chain and ATP levels in lung, as well as the formation of pulmonary edema. A decreased lung dynamic and static compliance, as well as an increase in respiratory system resistance, and a decrease in phospholipids content were observed. Physical exercise was able to totally prevent the decrease in succinate dehydrogenase and complex II activities and the formation of pulmonary edema. It also partially prevented the increase in respiratory system resistance, but did not prevent the decrease in dynamic and static compliance, as well as in phospholipids content. These findings suggest that the mitochondrial dysfunction may be one of the important contributors to lung damage and that physical exercise may be beneficial in this pathology, although it did not prevent all changes present in lung injury.

Cardiovascular dysfunction and pulmonary edema secondary to severe envenoming by Tityus pachyurus sting. Case report.

The scorpion envenomation is considered the second event by poisonous animals in importance around the world according to the World Health Organization. In Colombia there are 35 species of clinical significance, among them, the genus Tityus, which contains the most deadly scorpions in South America and is represented by 29 species of wide distribution in Colombia, which include Tityus pachyurus causing life-threatening events, especially in children. The present work shows the case of a 12 years old boy, from Tolemaida to 2 h of Bogotá D.C., who was stung by a scorpion on his right thigh, with the onset of intense signs and symptoms of local effect rapidly progressing to severe systemic involvement causing myocardial dysfunction, cardiovascular collapse and heart arrest, and his favorable response to adequate basic and advanced life support and use of scorpion-specific F(ab')2 antivenom.

[Pulmonary hypertension and lung edema at high altitude. Role of endothelial dysfunction and fetal programming]. / Hipertensión y edema pulmonar de altura. Rol de la disfunción endotelial y de la programación fetal.

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.

Echocardiographic parameters associated with pulmonary congestion in outpatients with Chagas' cardiomyopathy and non-chagasic cardiomyopathy.

INTRODUCTION: Despite significant left ventricular (LV) systolic dysfunction and cardiomegaly, pulmonary congestion does not seem to be a major finding in Chagas' cardiomyopathy (CC). This study sought to identify echocardiographic parameters associated with pulmonary congestion in CC and in dilated cardiomyopathy of other etiologies, such as non-CC (NCC), and to compare pulmonary venous hypertension between the two entities. METHODS: A total of 130 consecutive patients with CC and NCC, with similar echocardiographic characteristics, were assessed using Doppler echocardiography and chest radiography. Pulmonary venous vessel abnormalities were graded using a previously described pulmonary congestion score, and this score was compared with Doppler echocardiographic parameters. RESULTS: NCC patients were older than CC patients (62.4 ± 13.5 × 47.8 ± 11.2, p = 0.00), and there were more male subjects in the CC group (66.2% × 58.5%, p = 0.4). Pulmonary venous hypertension was present in 41 patients in the CC group (63.1%) and in 63 (96.9%) in the NCC group (p = 0.0), the mean lung congestion score being 3.2 ± 2.3 and 5.9 ± 2.6 (p = 0.0), respectively. On linear regression multivariate analysis, the E/e' ratio (ß = 0.13; p = 0.0), LV diastolic diameter (ß = 0.06; p = 0.06), left atrial diameter (ß = 0.51; p = 0.08), and right ventricular (RV) end-diastolic diameter (ß = 0.02; p = 0.48) were the variables that correlated with pulmonary congestion in both groups. CONCLUSIONS: Pulmonary congestion was less significant in patients with CC. The degree of LV of systolic and diastolic dysfunction and the RV diameter correlated with pulmonary congestion in both groups. The E/e' ratio was the hallmark of pulmonary congestion in both groups.

Echocardiographic parameters associated with pulmonary congestion in outpatients with Chagas' cardiomyopathy and non-chagasic cardiomyopathy / Parâmetros ecocardiográficos associados com a congestão pulmonar nas miocardiopatias chagásica e não-chagásica

INTRODUCTION: Despite significant left ventricular (LV) systolic dysfunction and cardiomegaly, pulmonary congestion does not seem to be a major finding in Chagas' cardiomyopathy (CC). This study sought to identify echocardiographic parameters associated with pulmonary congestion in CC and in dilated cardiomyopathy of other etiologies, such as non-CC (NCC), and to compare pulmonary venous hypertension between the two entities. METHODS: A total of 130 consecutive patients with CC and NCC, with similar echocardiographic characteristics, were assessed using Doppler echocardiography and chest radiography. Pulmonary venous vessel abnormalities were graded using a previously described pulmonary congestion score, and this score was compared with Doppler echocardiographic parameters. RESULTS: NCC patients were older than CC patients (62.4 ± 13.5 × 47.8 ± 11.2, p = 0.00), and there were more male subjects in the CC group (66.2% × 58.5%, p = 0.4). Pulmonary venous hypertension was present in 41 patients in the CC group (63.1%) and in 63 (96.9%) in the NCC group (p = 0.0), the mean lung congestion score being 3.2 ± 2.3 and 5.9 ± 2.6 (p = 0.0), respectively. On linear regression multivariate analysis, the E/e' ratio (β = 0.13; p = 0.0), LV diastolic diameter (β = 0.06; p = 0.06), left atrial diameter (β = 0.51; p = 0.08), and right ventricular (RV) end-diastolic diameter (β = 0.02; p = 0.48) were the variables that correlated with pulmonary congestion in both groups. CONCLUSIONS: Pulmonary congestion was less significant in patients with CC. The degree of LV of systolic and diastolic dysfunction and the RV diameter correlated with pulmonary congestion in both groups. The E/e' ratio was the hallmark of pulmonary congestion in both groups.

INTRODUÇÃO: Na miocardiopatia chagásica, ocorre uma discrepância entre os achados de disfunção ventricular e uma menor magnitude de congestão pulmonar em relação a outras miocardiopatias. Foram associados parâmetros morfofuncionais ecocardiográficos com achados de congestão pulmonar à radiografia do tórax em pacientes portadores de miocardiopatia chagásica e não chagásica, sendo a intensidade dos achados radiológicos comparada nos dois grupos. MÉTODOS: Foram recrutados 130 pacientes portadores de miocardiopatia chagásica e não chagásica, tendo os dois grupos parâmetros ecocardiográficos semelhantes. Todos realizaram o estudo radiológico do tórax, sendo atribuída uma pontuação aos achados sugestivos de congestão pulmonar, conforme escore já previamente estabelecido, sendo este comparado com os achados ecocardiográficos de disfunção ventricular. RESULTADOS: Os pacientes não chagásicos eram mais idosos (62,4±13,5 x 47,8±11,2, p=0,0), havendo um predomínio do sexo feminino nos chagásicos (66,2% x 58,5%, p=0,4). A hipertensão venocapilar pulmonar esteve presente em 41 chagásicos (63,1%) e 63 (96,9%) não-chagásicos (p=0,0), com escore da congestão pulmonar de 3,2±2,3 e 5,9±2,6 (p=0,0) respectivamente. Na análise de regressão linear, a relação E/e' (β=0,13; p=0,0), o diâmetro diastólico do ventrículo esquerdo (β=0,06; p=0,06), o diâmetro do átrio esquerdo (β=0,51; p=0,08) e o diâmetro diastólico final do ventrículo direito (β=0,02; p=0,48) foram as variáveis que mais se associaram com a congestão pulmonar nos dois grupos. CONCLUSÕES: Os pacientes chagásicos apresentaram um menor grau de congestão pulmonar. Os parâmetros de disfunção sistólica e diastólica associaram com a intensidade da congestão pulmonar, sendo a relação E/e' a variável que mais determinou a congestão pulmonar nos dois grupos.

Hipertensión y edema pulmonar de altura: Rol de la disfunción endotelial y de la programación fetal / Pulmonary hypertensión and lung edema at high altitude: Role of endothelial dysfunction and fetal programming

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.

Echocardiographic parameters associated with pulmonary congestion in Chagas cardiomyopathy.

INTRODUCTION: Discrepancy between the intensity of pulmonary congestion and the grade of cardiomegaly seems to be a common finding of Chagas cardiomyopathy, in spite of significant systolic dysfunction of the left ventricle. Its mechanism has not been established. The aim of this study was to investigate pulmonary congestion and to analyze if it correlated with Doppler echocardiographic parameters in patients with Chagas dilated cardiomyopathy. METHODS: Fifty-five patients with positive serology tests for Trypanosoma cruzi and Chagas dilated cardiomyopathy were studied. Chest x-rays, Doppler echocardiogram and plasmatic brain natriuretic peptide levels were obtained in all patients. The degree of pulmonary venous vessels changes on chest x-ray was graded using a pulmonary congestion score, and then compared to Doppler echocardiographic parameters. RESULTS: Mean age was 48.5 +/- 11.2 years and 29% were women. The majority (95%) of patients were in NYHA functional class I and II. Mild pulmonary congestion by chest x-ray was found in 80% of the patients. In a multivariate analysis, left ventricular ejection fraction, right ventricular TEI index and the color M-mode velocity correlated with the degree of pulmonary congestion. CONCLUSIONS: Pulmonary venous changes on chest x-rays are frequent, but usually mild in patients with Chagas dilated cardiomyopathy. The degree of pulmonary congestion correlates with Doppler echocardiographic left and right ventricular dysfunction and with color M-mode velocity.

Echocardiographic parameters associated with pulmonary congestion in Chagas cardiomyopathy / Parâmetros ecocardiográficos associados com a congestão pulmonar na miocardiopatia chagásica

INTRODUCTION: Discrepancy between the intensity of pulmonary congestion and the grade of cardiomegaly seems to be a common finding of Chagas cardiomyopathy, in spite of significant systolic dysfunction of the left ventricle. Its mechanism has not been established. The aim of this study was to investigate pulmonary congestion and to analyze if it correlated with Doppler echocardiographic parameters in patients with Chagas dilated cardiomyopathy. METHODS: Fifty-five patients with positive serology tests for Trypanosoma cruzi and Chagas dilated cardiomyopathy were studied. Chest x-rays, Doppler echocardiogram and plasmatic brain natriuretic peptide levels were obtained in all patients. The degree of pulmonary venous vessels changes on chest x-ray was graded using a pulmonary congestion score, and then compared to Doppler echocardiographic parameters. RESULTS: Mean age was 48.5 ± 11.2 years and 29 percent were women. The majority (95 percent) of patients were in NYHA functional class I and II. Mild pulmonary congestion by chest x-ray was found in 80 percent of the patients. In a multivariate analysis, left ventricular ejection fraction, right ventricular TEI index and the color M-mode velocity correlated with the degree of pulmonary congestion. CONCLUSIONS: Pulmonary venous changes on chest x-rays are frequent, but usually mild in patients with Chagas dilated cardiomyopathy. The degree of pulmonary congestion correlates with Doppler echocardiographic left and right ventricular dysfunction and with color M-mode velocity.

INTRODUÇÃO: Na miocardiopatia chagásica, é considerado haver uma menor intensidade de congestão pulmonar, mesmo na vigência de disfunção ventricular esquerda importante, não havendo ainda explicação definitiva para este fenômeno. O objetivo deste estudo foi de investigar a presença de congestão pulmonar na miocardiopatia chagásica e analisar se a intensidade da congestão esteve associada com parâmetros morfofuncionais ecocardiográficos de disfunção cardíaca. MÉTODOS: Cinquenta e cinco pacientes com sorologia positiva para o Trypanosoma cruzi e portadores de miocardiopatia chagásica foram estudados. Todos os pacientes foram submetidos ao estudo radiológico do tórax, ecocardiograma e dosagem plasmática do peptídeo natriurético cerebral. O grau de congestão pulmonar foi quantificado através de um escore da congestão pulmonar, e então comparado com os parâmetros ecocardiográficos. RESULTADOS: A idade média foi de 48.5 ± 1.2 anos e 29 por cento eram mulheres. A maior (95 por cento) parte dos pacientes encontrava-se na classe funcional I e II. Discreta congestão pulmonar à radiografia do tórax foi encontrada em 80 por cento dos pacientes. Na análise multivariada, a fração de ejeção do ventrículo esquerdo, o índice de TEI do ventrículo direito e a velocidade ao color M mode foram as variáveis que mais estiveram associadas com o grau de congestão pulmonar. CONCLUSÕES: Nos pacientes com miocardiopatia chagásica, as alterações do fluxo venoso pulmonar foram frequentes, porém discretas. O grau de congestão pulmonar associou com parâmetros ecocardiográficos de disfunção ventricular esquerda e direita e com a velocidade do color M mode.

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.