Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice

Objective: Gorticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: One hundred twenty-eight BALB/c mice (20-25 g). Interventions: Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Gexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 mu g, ALIp) or intraperitoneally (125 mu g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALlexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively). Measurements and Main Results: At 24 hrs, lung state elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interieukin-6, and transforming growth factor (TGF)-beta levels in bronchoatveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta 1 and TGF-beta 2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFN gamma, and TGF-beta 2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups. Conclusions. Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.

Pulmonary mechanic and lung histology injury induced by Crotalus durissus terrificus snake venom

In the present work we investigated the effects of Crotalus durissus terrificus venom (CdtV) on the pulmonary mechanic events [static and dynamic elastance, resistive (Delta P1) and viscoelastic pressures (Delta P2)] and histology after intramuscular injection of saline solution (control) or venom (0.6 mu g/g). The static and dynamic elastance values were increased significantly after 3 It of venom inoculation, but were reduced at control values in the other periods studied. The Delta P1 values that correspond to the resistive properties of lung tissue presented a significant increase after 6 h of CdtV injection, reducing to basal levels 12 h after the venom injection. In Delta P2 analysis, correspondent to viscoelastic components, an increase occurred 12 h after the venom injection, returning to control values at 24 h. CdtV also caused an increase of leukocytes recruitment (3-24 h) to the airways wall as well as to the lung parenchyma. In conclusion, C. durissus terrificus rattlesnake venom leads to lung injury which is reverted, after 24 h of inoculation. (c) 2008 Elsevier Ltd. All rights reserved.

Recruitment maneuver in pulmonary and extrapulmonary experimental acute lung injury

Objective. The aim of this study is to test the hypothesis that recruitment maneuvers (RMs) might act differently in models of pulmonary (p) and extrapulmonary (exp) acute lung injury (ALI) with similar transpulmonary pressure changes. Design: Prospective, randomized, controlled experimental study. Setting. University research laboratory. Subjects: Wistar rats were randomly divided into four groups. In control groups, sterile saline solution was intratracheally (0.1 mL, Cp) or intraperitoneally (1 mL, Cexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (100 jig, ALIp) or intraperitoneally (1 mg, ALIexp). After 24 hrs, animals were mechanically ventilated (tidal volume, 6 mL/kg; positive end-expiratory pressure, 5 cm H2O) and three RMs (pressure inflations to 40 cm H2O for 40 secs, 1 min apart) applied. Measurements and Main Results. Pao(2), lung resistive and viscoelastic pressures, static elastance, lung histology (light and electron microscopy), and type III procollagen messenger RNA expression in pulmonary tissue were measured before RMs and at the end of 1 hr of mechanical ventilation. Mechanical variables, gas exchange, and the fraction of area of alveolar collapse were similar in both ALI groups. After RMs, lung resistive and viscoelastic pressures and static elastance decreased more in ALIexp (255%,180%, and 118%, respectively) than in ALIp (103%, 59%, and 89%, respectively). The amount of atelectasis decreased more in ALIexp than in ALIp (from 58% to 19% and from 59% to 33%, respectively). RMs augmented type III procollagen messenger RNA expression only in the ALIp group (19%), associated with worsening in alveolar epithelium injury but no capillary endothelium lesion, whereas the ALIexp group showed a minor detachment of the alveolar capillary membrane. Conclusions. Given the same transpulmonary pressures, RMs are more effective at opening collapsed alveoli in ALIexp than in ALIp, thus improving lung mechanics and oxygenation with limited damage to alveolar epithelium.

Pulmonary morphofunctional effects of mechanical ventilation with high inspiratory air flow

Objective: Uncertainties about the numerous degrees of freedom in ventilator settings leave many unanswered questions about the biophysical determinants of lung injury. We investigated whether mechanical ventilation with high air flow could yield lung mechanical stress even in normal animals. Design. Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects. Thirty normal male Wistar rats (180-230 g). Interventions: Rats were ventilated for 2 hrs with tidal volume of 10 mL/kg and either with normal inspiratory air flow (V`) of 10 mL/s (F10) or high V` of 30 mL/s (F30). In the control group, animals did not undergo mechanical ventilation. Because high flow led to elevated respiratory rate (200 breaths/min) and airway peak inspiratory pressure (PIP,aw = 17 cm H2O), two additional groups were established to rule out the potential contribution of these variables: a) normal respiratory rate = 100 breaths/min and V` = 30 mL/sec; and b) PIP,aw = 17 cm H2O and V` 10 mL/sec. Measurements and Main Results: Lung mechanics and histology (light and electron microscopy), arterial blood gas analysis, and type III procollagen messenger RNA expression in lung tissue were analyzed. Ultrastructural microscopy was similar in control and F10 groups. High air flow led to increased lung plateau and peak pressures, hypoxemia, alveolar hyperinflation and collapse, pulmonary neutrophilic infiltration, and augmented type III procollagen messenger RNA expression compared with control rats. The reduction of respiratory rate did not modify the morphofunctional behavior observed in the presence of increased air flow. Even though the increase in peak pressure yielded mechanical and histologic changes, type III procollagen messenger RNA expression remained unaltered. Conclusions: Ventilation with high inspiratory air flow may lead to high tensile and shear stresses resulting in lung functional and morphologic compromise and elevation of type III procollagen messenger RNA expression.

Cardiopulmonary Effects of Matching Positive End-Expiratory Pressure to Abdominal Pressure in Concomitant Abdominal Hypertension and Acute Lung Injury

Background: To evaluate the cardiopulmonary effects of positive end-expiratory pressure (PEEP) equalization to intra-abdominal pressure (IAP) in an experimental model of intra-abdominal hypertension (IAH) and acute lung injury (ALI). Methods: Eight anesthetized pigs were submitted to IAH of 20 mm Hg with a carbon dioxide insufflator for 30 minutes and then submitted to lung lavage with saline and Tween (2.5%). Pressure x volume curves of the respiratory system were performed by a low flow method during IAH and ALI, and PEEP was subsequently adjusted to 27 cm center dot H(2)O for 30 minutes. Results: IAH decreases pulmonary and respiratory system static compliances and increases airway resistance, alveolar-arterial oxygen gradient, and respiratory dead space. The presence of concomitant ALI exacerbates these findings. PEEP identical to AP moderately improved oxygenation and respiratory mechanics; however, an important decline in stroke index and right ventricle ejection fraction was observed. Conclusions: Simultaneous IAH and ALI produce important impairments in the respiratory physiology. PEEP equalization to AP may improve the respiratory performance, nevertheless with a secondary hemodynamic derangement.

Time course of haemodynamic, respiratory and inflammatory disturbances induced by experimental acute pulmonary polystyrene microembolism

Background and objective The time course of cardiopulmonary alterations after pulmonary embolism has not been clearly demonstrated and nor has the role of systemic inflammation on the pathogenesis of the disease. This study aimed to evaluate over 12 h the effects of pulmonary embolism caused by polystyrene microspheres on the haemodynamics, lung mechanics and gas exchange and on interleukin-6 production. Methods Ten large white pigs (weight 35-42 kg) had arterial and pulmonary catheters inserted and pulmonary embolism was induced in five pigs by injection of polystyrene microspheres (diameter similar to 300 mu mol l(-1)) until a value of pulmonary mean arterial pressure of twice the baseline was obtained. Five other animals received only saline. Haemodynamic and respiratory data and pressure-volume curves of the respiratory system were collected. A bronchoscopy was performed before and 12 h after embolism, when the animals were euthanized. Results The embolism group developed hypoxaemia that was not corrected with high oxygen fractions, as well as higher values of dead space, airway resistance and lower respiratory compliance levels. Acute haemodynamic alterations included pulmonary arterial hypertension with preserved systemic arterial pressure and cardiac index. These derangements persisted until the end of the experiments. The plasma interleukin-6 concentrations were similar in both groups; however, an increase in core temperature and a nonsignificant higher concentration of bronchoalveolar lavage proteins were found in the embolism group. Conclusion Acute pulmonary embolism induced by polystyrene microspheres in pigs produces a 12-h lasting hypoxaemia and a high dead space associated with high airway resistance and low compliance. There were no plasma systemic markers of inflammation, but a higher central temperature and a trend towards higher bronchoalveolar lavage proteins were found. Eur J Anaesthesiol 27:67-76 (C) 2010 European Society of Anaesthesiology.

Human bocavirus respiratory infections in children

Human bocavirus (HBoV) was recently identified in respiratory samples from patients with acute respiratory infections and has been reported in different regions of the world. To the best of our knowledge, HBoV has never been reported in respiratory infections in Brazil. Nasopharyngeal aspirates were collected from patients aged <5 years hospitalized in 2005 with respiratory infections in Ribeirao Preto, southeast Brazil, and tested by polymerase chain reaction (PCR) for HBoV. HBoV-positive samples were further tested by PCR for human respiratory syncytial virus, human metapneumovirus, human coronaviruses 229E and OC43, human influenza viruses A and B, human parainfluenza viruses 1, 2 and 3, human rhinovirus and human adenovirus. HBoV was detected in 26/248 (10.5%) children of which 21 (81%) also tested positive for other respiratory viruses. Despite the high rates of co-infections, no significant differences were found between HBoV-positive patients with and without co-infections with regard to symptoms.

Effects of Chronic Exposure to Crack Cocaine on the Respiratory Tract of Mice

Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.

Cavopulmonary anastomosis improves left ventricular assist device support in acute biventricular failure

Objective: Right ventricular failure during left ventricular assist device (WAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavopulmonary anastomosis on right ventricular loading and WAD performance in a model of severe biventricular failure. Methods: LVAD support was performed by means of centrifugal pump implantation in 14 anesthetized dogs (20-30 kg) with severe biventricular failure obtained by ventricular fibrillation induction. Animals were randomized to be submitted to classical cavopulmonary anastomosis (Glenn shunt) or to control group and were maintained under WAD support for 2 h. Left and right atrial, right ventricular and systemic pressures were monitored, white total pulmonary flow was simultaneously recorded by transonic flowmeters located on the superior vena cava and pulmonary trunk. Blood gas and venous lactate determinations were also obtained. Results: Ventricular fibrillation maintenance resulted in acute WAD performance impairment after 90 min in the control group, while animals with Glenn circuit maintained normal WAD pump flow (55 +/- 13 ml kg(-1) min(-1) vs 21 +/- 4 ml kg(-1) min(-1), p < 0.001) and better peripheral perfusion (blood lactate of 29 +/- 10 pg/ml vs 46 +/- 9 pg/ml, p < 0.001). Left and right atrial pressures did not change significantly, while right ventricular pressure was tower in animals with Glenn circuit (13 +/- 3 mmHg vs 22 +/- 8 mmHg, p = 0.005). Right ventricular unloading with Glenn shunt also resulted in superior total pulmonary flow (59 +/- 13 ml kg(-1) min(-1) vs 17 +/- 3 ml kg(-1) min(-1), p < 0.001). Conclusion: The concomitant use of cavopulmonary anastomosis during LVAD support in a model of severe biventricular failure limited right ventricular overloading and resulted in better hemodynamic performance. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Improvements in the 6-Min Walk Test and Spirometry Following Thoracentesis for Symptomatic Pleural Effusions

Background: Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. Methods: Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV, were analyzed before and 48 h after the removal of large pleural effusions. Results: The mean fluid removed was 1,564 +/- 695 mL. After the procedure, values of FVC, FEV and 6-min walk distance increased (P<.001), whereas dyspnea decreased (P<.001). Statistical correlations (P<.001) between 6-min walk distance and FVC (r=0.725) and between 6-min walk distance and FEV, (r=0.661) were observed. Correlations also were observed between the deltas (prethoracentesis X postthoracentesis) of the 6-min walk test and the percentage of FVC (r=0.450) and of FEV, (r=0.472) divided by the volume of fluid removed (P<.05). Conclusion: In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities. CHEST 2011; 139(6):1424-1429

Influence of ventilatory settings on static and functional haemodynamic parameters during experimental hypovolaemia

Background and objective The influence of ventilatory settings on static and functional haemodynamic parameters during mechanical ventilation is not completely known. The purpose of this study was to evaluate the effect of positive end-expiratory pressure, tidal volume and inspiratory to expiratory time ratio variations on haemodynamic parameters during haemorrhage and after transfusion of shed blood. Methods Ten anaesthetized pigs were instrumented and mechanically ventilated with a tidal volume of 8 ml kg(-1), a positive end-expiratory pressure of 5 cmH(2)O and an inspiratory to expiratory ratio of 1 : 2. Then, they were submitted in a random order to different ventilatory settings (tidal volume 16 ml kg(-1), positive end-expiratory pressure 15 cmH(2)O or inspiratory to expiratory time ratio 2: 1). Functional and static haemodynamic parameters (central venous pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic volume and pulse pressure variation) were evaluated at baseline, during hypovolaemia (withdrawal of 20% of estimated blood volume) and after an infusion of withdrawn blood (posttransfusion). Results During baseline, a positive end-expiratory pressure of 15cmH(2)O significantly increased pulmonary artery occlusion pressure from 14.6 +/- 1.6 mmHg to 17.4 +/- 1.7 mmHg (P<0.001) and pulse pressure variation from 15.8 +/- 8.5% to 25.3 +/- 9.5% (P<0.001). High tidal volume increased pulse pressure variation from 15.8 8.5% to 31.6 +/- 10.4% (P<0.001), and an inspiratory to expiratory time ratio of 2: 1 significantly increased only central venous pressure. During hypovolaemia, high positive end-expiratory pressure influenced all studied variables, and high tidal volume strongly increased pulse pressure variation (40.5 +/- 12.4% pre vs. 84.2 +/- 19.1 % post, P<0.001). The inversion of the inspiratory to expiratory time ratio only slightly increased filling pressures during hypovolaemia, without without affecting pulse pressure variation or right ventricle end-diastolic volume. Conclusion We concluded that pulse pressure variation measurement is influenced by cyclic variations in intrathoracic pressure, such as those caused by augmentations in tidal volume. The increase in mean airway pressure caused by positive end-expiratory pressure affects cardiac filling pressures and also pulse pressure variation, although to a lesser extent. Inversion of the inspiratory to expiratory time ratio does not induce significant changes in static and functional haemodynamic parameters. Eur J Anaesthesiol 26:66-72 (c) 2009 European Society of Anaesthesiology.

The epidemiology of acute respiratory failure in hospitalized patients: A Brazilian prospective cohort study

Purpose: The purpose of this study was to assess risk factors associated with the development of acute respiratory failure (ARF) and death in a general intensive care unit (ICU). Materials and Methods: Adults who were hospitalized at 12 surgical and nonsurgical ICUs were prospectively followed up. Multivariable analyses were realized to determine the risk factors for ARF and point out the prognostic factors for mortality in these patients. Results: A total of 1732 patients were evaluated, with an ARF prevalence of 57%. Of the 889 patients who were admitted without ARF, 141 (16%) developed this syndrome in the ICU. The independent risk factors for developing ARF were 64 years of age or older, longer time between hospital and ICU admission, unscheduled surgical or clinical reason for ICU admission, and severity of illness. Of the 984 patients with ARF, 475 (48%) died during the ICU stay. Independent prognostic factors for death were age older than 64 years, time between hospital and ICU admission of more than 4 days, history of hematologic malignancy or AIDS, the development of ARF in ICU, acute lung injury, and severity of illness. Conclusions: Acute respiratory failure represents a large percentage of all ICU patients, and the high mortality is related to some preventable factors such as the time to ICU admission. (C) 2011 Elsevier Inc. All rights reserved.

Molecular Characterization of Strains of Respiratory Syncytial Virus Identified in a Hematopoietic Stem Cell Transplant Outpatient Unit Over 2 Years: Community or Nosocomial Infection?

Respiratory syncytial virus (RSV) is recognized as the leading cause of nosocomial respiratory infection among hematopoietic stem cell transplant (HSCT) recipients, causing considerable morbidity and mortality. RSV is easily transmitted by contact with contaminated surfaces, and in HSCT units, more than 50% of RSV infections have been characterized as of nosocomial origin. From April 2001 to October 2002, RSV was identified by direct immunofluorescent assay in 42 symptomatic HSCT recipients. Seven RSV strains from 2001 and 12 RSV strains from 2002 were sequenced. RNA extraction, cDNA synthesis, and seminested polymerase chain reaction (PCR) with primers complementary to RSV genes G and F were pet-formed. PCR products were analyzed by nucleotide sequencing of the C-terminal region of gene G for typing (in group A or B). Of the 7 strains analyzed in 2001, only 2 belonged to group B; the other 5 belonged to group A. Of these 7 strains, 3 were identical and were from recipients receiving outpatient care. In 2002, of the 12 strains analyzed, 3 belonged to group A and the other 9 belonged to group B. Of these 9 strains, 7 were genetically identical and were also from recipients receiving outpatient care. Therefore, multiple strains of RSV cocirculated in the hematopoietic stem cell transplant units (ward and outpatient units) between 2001 and 2002. Nosocomial transmission was more likely to occur at the HSCT outpatient unit than in the HSCT ward. Infection control practices should also be implemented in the outpatient setting.

Comparative study of pressure- and volume-controlled ventilation on pulse pressure variation in a model of hypovolaemia in rabbits

Background and objective: Dynamic indices represented by systolic pressure variation and pulse pressure variation have been demonstrated to be more accurate than filling pressures in predicting fluid responsiveness. However, the literature is scarce concerning the impact of different ventilatory modes on these indices. We hypothesized that systolic pressure variation or pulse pressure variation could be affected differently by volume-controlled ventilation and pressure-controlled ventilation in an experimental model, during normovolaemia and hypovolaemia. Method: Thirty-two anaesthetized rabbits were randomly allocated into four groups according to ventilatory modality and volaemic status where G1-ConPCV was the pressure-controlled ventilation control group, G2-HemPCV was associated with haemorrhage, G3-ConVCV was the volume-controlled ventilation control group and G4-HemVCV was associated with haemorrhage. In the haemorrhage groups, blood was removed in two stages: 15% of the estimated blood volume withdrawal at M1, and, 30 min later, an additional 15% at M2. Data were submitted to analysis of variance for repeated measures; a value of P < 0.05 was considered to be statistically significant. Results: At MO (baseline), no significant differences were observed among groups. At M1, dynamic parameters differed significantly among the control and hypovolaemic groups (P < 0.05) but not between ventilation modes. However, when 30% of the estimated blood volume was removed (M2), dynamic parameters became significantly higher in animals under volume-controlled ventilation when compared with those under pressure-controlled ventilation. Conclusions: Under normovolaemia and moderate haemorrhage, dynamic parameters were not influenced by either ventilatory modalities. However, in the second stage of haemorrhage (30%), animals in volume-controlled ventilation presented higher values of systolic pressure variation and pulse pressure variation when compared with those submitted to pressure-controlled ventilation.