Characterization of oleic acid-induced acute respiratory distress syndrome model in rat.

Animal studies using oleic acid (OA) model to produce acute respiratory distress syndrome (ARDS) have been inconsistent. Therefore, the present study was undertaken to establish an acute model of ARDS in rats using OA and to characterize its effect on cardio-respiratory parameters and lethality. The trachea, jugular vein and femoral artery of anesthetized adult rats were cannulated. A dose of OA (30-90 µL; iv) was injected in each animal and changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were recorded. Minute ventilation and PaO2/FiO2 (P/F) ratio were also determined. At the end, lungs were excised for determination of pulmonary water content and histological examination. At all doses of OA, there was immediate decrease followed by increase in RF, however at 75 and 90 µL of OA, RF decreased abruptly and the animals died by 63 ± 8.2 min and 19 ± 6.3 min; respectively. In all the groups, HR and MAP changes followed the respiratory changes. The minute ventilation increased in a dose-dependent manner while the values of P/F ratio decreased correspondingly. Pulmonary edema was induced at all doses. Histological examination of the lung showed alveolar damage, microvascular congestion, microvascular injury, infiltration of inflammatory cells, pulmonary edema and necrosis in a dose-dependent manner. With these results, OA can be used to induce different grades of ARDS in rats and OA doses of 50, 60 and 75 µL resemble mild, moderate and severe forms of ARDS respectively. Hence, OA model serves as a useful tool to study the pathophysiology of ARDS.

Mechanical ventilation and volutrauma: study in vivo of a healthy pig model

Mechanical ventilation is essential in intensive care units. However, it may itself induce lung injury. Current studies are based on rodents, using exceptionally large tidal volumes for very short periods, often after a "priming" pulmonary insult. Our study deepens a clinically relevant large animal model, closely resembling human physiology and the ventilator setting used in clinic settings. Our aim was to evaluate the pathophysiological mechanisms involved in alveolo/capillary barrier damage due to mechanical stress in healthy subjects. We randomly divided 18 pigs (sedated with medetomidine/tiletamine-zolazepam and anesthetised with thiopental sodium) into three groups (n=6): two were mechanically ventilated (tidal volume of 8 or 20 ml/kg), the third breathed spontaneously for 4 hours, then animals were sacrificed (thiopental overdose). We analyzed every 30' hemogasanalysis and the main circulatory and respiratory parameters. Matrix gelatinase expression was evaluated on bronchoalveolar lavage fluid after surgery and before euthanasia. On autoptic samples we performed zymographic analysis of lung, kidney and liver tissues and histological examination of lung. Results evidenced that high Vt evoked profound alterations of lung mechanics and structure, although low Vt strategy was not devoid of side effects, too. Unexpectedly, also animals that were spontaneously breathing showed a worsening of the respiratory functions.

Evaluation of lung infiltration score to predict postural hypoxemia in ventilated acute respiratory distress syndrome patients and the lateralization of skin pressure sore.

Context: Mechanical ventilation with positive end expiratory pressure (PEEP) is associated with unequal aeration of lungs in acute respiratory distress syndrome (ARDS) patients. Therefore, patients may develop asymmetric atelectasis and postural hypoxemia during lateral positioning. Aims: To validate proposed lung infiltration score (LIS) based on chest x-ray to predict postural hypoxemia and lateralization of skin sores in ARDS patients. Settings and Design: University hospital ICU. Prospective, observational study of consecutive patients. Materials and Methods: Sixteen adult patients of both genders on mechanical ventilation with PEEP for 24 to <48 hours. On chest x-ray, 6 segments were identified on each lung. The proposed LIS points (0- normal; 1- patchy infiltrates; 2- white infiltrates matching heart shadow) were assigned to each segment. Without changing ventilation parameters, supine, left and right lateral positions at 45° tilt were randomly changed. At the end of 20 minutes of ventilation in each position, we observed arterial oxygen saturation, hemodynamic and arterial blood gases. Later, position change protocol (4 hourly) was practiced in ICU, and skin pressure sore grading was noted within a week of ICU stay. Statistical Analysis Used: Nonparametric Bland and Altman correlation analysis, ANOVA and Student t test. Results: Arterial oxygenation (PaO 2 /FiO 2 = 313± 145.6) was significantly (P<0.01) higher in better lung (lower LIS)-down position than supine (PaO 2 /FiO 2 = 199± 70.2) or a better lung-up position (PaO 2 /FiO 2 = 165± 64.8). The positioning-related arterial oxygenation was significant (P< 0.05) at LIS asymmetry ≥3 between two lungs. Conclusions: The LIS mapping on chest x-ray was useful to differentiate between asymmetric lung disease and postural hypoxemia in ICU patients, which predisposed patients to early skin sore changes on higher LIS side.

Síndrome da angústia respiratória do adulto por embolia gordurosa no período pós-operatório de lipoaspiração e lipoenxertia / Adult respiratory distress syndrome due to fat embolism in the postoperative period following liposuction and fat grafting

A embolia gordurosa é definida como a ocorrência de bloqueio mecânico da luz vascular por gotículas circulantes de gordura. Acomete principalmente o pulmão, podendo afetar também o sistema nervoso central, a retina e a pele. A síndrome da embolia gordurosa é uma disfunção desses órgãos causada pelos êmbolos gordurosos. As causas mais comuns de embolia gordurosa e síndrome da embolia gordurosa são as fraturas de ossos longos, mas há relatos de sua ocorrência após procedimentos estéticos. O diagnóstico é clínico, e o tratamento ainda se restringe a medidas de suporte. Apresentamos o caso de uma paciente que evoluiu com síndrome da angústia respiratória do adulto por embolia gordurosa no período pós-operatório de lipoaspiração e lipoenxertia e respondeu bem às manobras de recrutamento alveolar e à ventilação mecânica protetora.Apresentamos também uma análise epidemiológica e fisiopatológica da síndrome da embolia gordurosa após procedimentos estéticos.

Fat embolism is defined as mechanical blockage of the vascular lumen by circulating fat globules. Although it primarily affects the lungs, it can also affect the central nervous system, retina, and skin. Fat embolism syndrome is a dysfunction of these organs caused by fat emboli. The most common causes of fat embolism and fat embolism syndrome are long bone fractures, although there are reports of its occurrence after cosmetic procedures. The diagnosis is made clinically, and treatment is still restricted to support measures. We report the case of a female patient who developed adult respiratory distress syndrome due to fat embolism in the postoperative period following liposuction and fat grafting. In this case, the patient responded well to alveolar recruitment maneuvers and protective mechanical ventilation. In addition, we present an epidemiological and pathophysiological analysis of fat embolism syndrome after cosmetic procedures.

Utilization of the lower inflection point of the pressure-volume curve results in protective conventional ventilation comparable to high frequency oscillatory ventilation in an animal model of acute respiratory distress syndrome

INTRODUCTION: Studies comparing high frequency oscillatory and conventional ventilation in acute respiratory distress syndrome have used low values of positive end-expiratory pressure and identified a need for better recruitment and pulmonary stability with high frequency. OBJECTIVE: To compare conventional and high frequency ventilation using the lower inflection point of the pressure-volume curve as the determinant of positive end-expiratory pressure to obtain similar levels of recruitment and alveolar stability. METHODS: After lung lavage of adult rabbits and lower inflection point determination, two groups were randomized: conventional (positive end-expiratory pressure = lower inflection point; tidal volume=6 ml/kg) and high frequency ventilation (mean airway pressures= lower inflection point +4 cmH2O). Blood gas and hemodynamic data were recorded over 4 h. After sacrifice, protein analysis from lung lavage and histologic evaluation were performed. RESULTS: The oxygenation parameters, protein and histological data were similar, except for the fact that significantly more normal alveoli were observed upon protective ventilation. High frequency ventilation led to lower PaCO2 levels. DISCUSSION: Determination of the lower inflection point of the pressure-volume curve is important for setting the minimum end expiratory pressure needed to keep the airways opened. This is useful when comparing different strategies to treat severe respiratory insufficiency, optimizing conventional ventilation, improving oxygenation and reducing lung injury. CONCLUSIONS: Utilization of the lower inflection point of the pressure-volume curve in the ventilation strategies considered in this study resulted in comparable efficacy with regards to oxygenation and hemodynamics, a high PaCO2 level and a lower pH. In addition, a greater number of normal alveoli were found after protective conventional ventilation in an animal model of acute respiratory distress syndrome.

Precisão do diagnóstico clínico da síndrome do desconforto respiratório agudo quando comparado a achados de necropsia / Accuracy of clinical diagnosis of acute respiratory distress syndrome in comparison with autopsy findings

OBJETIVO: Comparar a definição de síndrome do desconforto respiratório agudo (SDRA) estabelecida pela American-European Consensus Conference (AECC, Conferência Americano-Européia) com achados de necropsia. MÉTODOS: Avaliaram-se todos os pacientes que morreram na unidade de terapia intensiva do Hospital Universitário da Universidade Federal de Juiz de Fora entre 1995 e 2003 e que foram submetidos à necropsia. Seus prontuários foram revisados para estabelecer a presença ou não dos critérios clínicos de SDRA, cujo diagnóstico histológico foi definido pela presença de dano alveolar difuso (DAD). RESULTADOS: No período, 592 pacientes faleceram e 22 foram submetidos à necropsia. Destes, 10 pacientes (45 por cento) preencheram os critérios de SDRA pela AECC e sete (32 por cento) preencheram os critérios histopatológicos de DAD. A sensibilidade da definição clínica foi de 71 por cento (IC95 por cento: 36-92 por cento) e a especificidade foi de 67 por cento (IC95 por cento: 42-85 por cento). Os valores preditivos positivo e negativo foram, respectivamente, 50 e 83 por cento; e as razões de verossimilhança positiva e negativa foram, respectivamente, 2,33 e 0,47. Os achados histopatológicos nos cinco pacientes que preencheram os critérios clínicos de SDRA, mas não apresentavam DAD, foram pneumonia (n = 2), embolia pulmonar (n = 1), tuberculose (n = 1) e criptococose (n = 1). CONCLUSÃO: A precisão dos critérios da AECC para diagnóstico de SDRA não é tão boa. Em função do baixo valor preditivo positivo e da baixa razão de verossimilhança positiva do diagnóstico clínico, outras hipóteses devem ser consideradas quando há suspeita de SDRA.

OBJECTIVE: To compare the American-European Consensus Conference (AECC) definition of acute respiratory distress syndrome (ARDS) to autopsy findings. METHODS: All patients who died in the intensive care unit of the Federal University of Juiz de Fora University Hospital between 1995 and 2003 and were submitted to autopsy were included in the study. Patient clinical charts were reviewed to establish whether cases met the AECC criteria for a diagnosis of ARDS, histologically defined as the presence of diffuse alveolar damage (DAD). RESULTS: During the study period, 592 patients died, and 22 were submitted to autopsy. Of those 22 patients, 10 (45 percent) met the AECC criteria, and 7 (32 percent) met the histopathological criteria for DAD. The AECC clinical criteria presented a sensitivity of 71 percent (95 percentCI: 36-92 percent) and a specificity of 67 percent (95 percentCI: 42-85 percent). The positive and negative predictive values were, respectively, 50 and 83 percent, whereas the positive and negative likelihood ratios were, respectively, 2.33 and 0.47. The histopathological findings in the 5 patients who met AECC criteria but did not present DAD were pneumonia (n = 2), pulmonary embolism (n = 1), tuberculosis (n = 1), and cryptococcosis (n = 1). CONCLUSION: The accuracy of the AECC definition of ARDS was godless than satisfactory. Due to the low positive predictive value and the low positive likelihood ratio, other hypotheses must be considered when ARDS is suspected.

Pathology and pathophysiology of pulmonary manifestations in leptospirosis

Leptospirosis is a re-emerging zoonosis occurring as large outbreaks throughout the world caused by Leptospira interrogans. The incidence of pulmonary involvement in leptospirosis has been reported to be increasing in the last years, affecting up to 70 percent of the patients. Alveolar hemorrhage presented as dyspnea and hemoptysis is the main pulmonary manifestation. The emergence of massive hemoptysis and acute respiratory distress syndrome has characterized the recent changes reported in the clinical patterns of leptospirosis. The pulmonary involvement has been emerged as a serious life threat, becoming the main cause of death due to leptospirosis in some countries. In this review we present the main clinical and pathological manifestations of pulmonary involvement in leptospirosis, with special focus on recent data concerning the pathophysiological mechanisms underlying lung injury.

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage / Imunomarcação não homogênea das membranas hialinas na sindrome da angustia respiratório do adulto pulmonar, extrapulmonar e idiopática

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (a-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65 percent ± 3.24 percent), while extrapulmonary diffuse alveolar damage (9.52 percent ± 3.64 percent) and idiopathic diffuse alveolar damage (7.34 percent ± 2.11 percent) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36 percent ± 3.12 percent), extrapulmonary (16.12 percent ± 4.58 percent), and idiopathic (13.74 ± 4.20 percent) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12 percent ± 6.25 percent) than extrapulmonary diffuse alveolar damage...

OBJETIVO: Determinar a natureza da membrana hialina nas diferentes manifestações do dano alveolar difuso [pulmonar e extrapulmonar síndrome do desconforto respiratório] e idiopático [pneumonia intersticial aguda]. MATERIAIS E MÉTODOS: Espécimes pulmonares foram obtidos de 17 pacientes com SDRA e 9 pacientes com pneumonia intersticial aguda e separados em três diferentes grupos: (a) dano alveolar difuso pulmonar (DADp) (n=8) constituído por casos de pneumonia, (b) dano alveolar difuso extrapulmonar (DADexp) (n=9) constituído por casos de sepse e choque séptico e (c) dano alveolar difuso idiopático (DADi) (n=9) constituído por casos idopáticos (ou pneumonia intersticial aguda). As características das membranas hialinas do padrão histológico de dano alveolar difuso foram examinadas usando vários tipos de anticorpos. Os anticorpos usados foram surfactante apoproteina A (SP-A), anti-citokeratina 7 (CK7), citokeratina 8 (CK8), alfa actina de músculo liso (a-SMA), citokeratina AE1/AE3 (AE1/AE3) e antígeno relacionado ao fator VIII (Fator VIII). RESULTADOS: Observaram-se aumentos maiores da quantidade de membrana hialina no dano alveolar difuso pulmonar (12.65 ± 3.24 por cento), intermediários no dano alveolar difuso extrapulmonar (9.52 ± 3.64 por cento) e baixos no dano alveolar difuso idiopático (7.34 ± 2.11 por cento) respectivamente, esta diferencia foi estatística significante entre o dano alveolar difuso pulmonar e o dano alveolar difuso idiopático (p<0.05). Não se encontrou significância estatística para a quantidade de imunomarcação de Sp-A nos grupos de dano alveolar difuso pulmonar (15.36 ± 3.12 por cento), extrapulmonar (16.12 ± 4.58 por cento) e idiopático (13.74 ± 4.20 por cento). Com relação ao Fator VIII, nós encontramos maiores aumentos da imunomarcação da membrana hialina no grupo dano alveolar difuso idiopático (14.12 ± 6.25 por cento) do que no dano alveolar difuso extrapulmonar (3.93 ± 2.86 por cento), com significância estatística (p<0.001). Da mesma...

Lung tissue remodeling in the acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro¡liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patientÆs prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

Acute Respiratory Distress Syndrome Induced by Adenovirus in an Otherwise Healthy Woman

Acute respiratory distress syndrome (ARDS) caused by adenovirus is a rare event in healthy adults, especially in non- military settings. Although treatment with intravenous ribavirin has been reported, supportive care, including mechanical ventilation, is known to be the main stay in the treatment of ARDS caused by adenovirus, with high-dose steroid treatment having rarely been reported. We report our experience with a 41-year-old, otherwise healthy, woman with ARDS, treated with high-dose steroid and mechanical ventilatory support.

Morphological changes of carotid bodies in acute respiratory distress syndrome: a morphometric study in humans

Carotid bodies are chemoreceptors sensitive to a fall of partial oxygen pressure in blood (hypoxia). The morphological alterations of these organs in patients with chronic obstructive pulmonary disease (COPD) and in people living at high altitude are well known. However, it is not known whether the histological profile of human carotid bodies is changed in acute clinical conditions such as acute respiratory distress syndrome (ARDS). The objective of the present study was to perform a quantitative analysis of the histology of carotid bodies collected from patients who died of ARDS. A morphometric study of carotid bodies collected during routine autopsies was carried out on three groups: patients that died of non-respiratory diseases (controls, N = 8), patients that presented COPD and died of its complications or associated diseases (N = 7), and patients that died of ARDS (N = 7). Morphometric measurements of the volume fraction of clusters of chief cells were performed in five fields on each slide at 40X magnification. The numerical proportion of the four main histological cell types (light, dark, progenitor and sustentacular cells) was determined analyzing 10 fields on each slide at 400X magnification. The proportion of dark cells was 0.22 in ARDS patients, 0.12 in controls (P<0.001), and 0.08 in the COPD group. The proportion of light cells was 0.33 (ARDS), 0.44 (controls) (P<0.001), and 0.36 (COPD). These findings suggest that chronic and acute hypoxia have different effects on the histology of glomic tissue

Hemoptise/s e síndrome de angústia respiratória do adulto como causas de morte na leptospirose: mudanças de padröes clínicos e anatomopatológicos / Hemoptysis ant the adult respiratory distress syndrome as the causes of death leptospirosis: changes in the clinical and anatomopathological patterns

A leptospirose humana, uma das principais endemias dos centros urbanos no Brasil, vem crescendo de forma dramática nas três últimas décadas, com prevalência após enchentes causadas pelas chuvas de veräo. Säo descritas as recentes modificaçöes de seus padröes clínicos em nossa regiäo, constituídas pelo surgimento de hemoptise/s maciça/s e da síndrome de angústia respiratória do adulto, ou de ambas associadamente. Essas evidentes mudanças situadas nas estruturas respiratórias depontaram como séria ameaça à vida e como mecanismos de morte, passando a representar entre nós, por sua grande freqüência, a principal causa de óbito na leptospirose. A nova face da doença impöe revisäo dos conceitos sobre sua gravidade e especulaçäo sobre a patogenia dessas alteraçöes. A evoluçäo fatal dos seis pacientes descritos, dois deles sem icterícia e sem insuficiência renal, mostra a grandeza do desafio

Pulmón de choque en el niño: síndrome de insuficiencia respiratoria aguda / Schock lung in the child: acute respiratory insufficiency syndrome

Se estudiaron los pulmones de 50 pacientes fallecidos con sintomatología y/o diagnóstico clínico de choque. Todos tuvieron septicemia. Las lesiones histológicas de los pulmones más frecuentes fueron: engrosamiento de los septos interalveolares por edema y/o acumulamiento de leucocitos, hemorragias focales, material hialino intraalveolar y microtrombos de fibrina, lesiones debidas a un daño profundo de los endotelios, membranas basales y alveolocitos y que clínicamente corresponden a insuficiencia respiratoria, frecuente causa de muerte en pacientes con choque