Regional Lung Recruitability During Pneumoperitoneum Depends on Chest Wall Elastance - A Mechanical and Computed Tomography Analysis in Rats.

Background: Laparoscopic surgery with pneumoperitoneum increases respiratory system elastance due to the augmented intra-abdominal pressure. We aim to evaluate to which extent positive end-expiratory pressure (PEEP) is able to counteract abdominal hypertension preventing progressive lung collapse and how rib cage elastance influences PEEP effect. Methods: Forty-four Wistar rats were mechanically ventilated and randomly assigned into three groups: control (CTRL), pneumoperitoneum (PPT) and pneumoperitoneum with restricted rib cage (PPT-RC). A pressure-volume (PV) curve followed by a recruitment maneuver and a decremental PEEP trial were performed in all groups. Thereafter, animals were ventilated using PEEP of 3 and 8 cmH2O divided into two subgroups used to evaluate respiratory mechanics or computed tomography (CT) images. In 26 rats, we compared respiratory system elastance (Ers) at the two PEEP levels. In 18 animals, CT images were acquired to calculate total lung volume (TLV), total volume and air volume in six anatomically delimited regions of interest (three along the cephalo-caudal and three along the ventro-dorsal axes). Results: PEEP of minimal Ers was similar in CTRL and PPT groups (3.8 ± 0.45 and 3.5 ± 3.89 cmH2O, respectively) and differed from PPT-RC group (9.8 ± 0.63 cmH2O). Chest restriction determined a right- and downward shift of the PV curve, increased Ers and diminished TLV and lung aeration. Increasing PEEP augmented TLV in CTRL group (11.8 ± 1.3 to 13.6 ± 2 ml, p < 0.05), and relative air content in the apex of PPT group (3.5 ± 1.4 to 4.6 ± 1.4% TLV, p < 0.03) and in the middle zones in PPT-RC group (21.4 ± 1.9 to 25.3 ± 2.1% TLV cephalo-caudally and 18.1 ± 4.3 to 22.0 ± 3.3% TLV ventro-dorsally, p < 0.005). Conclusion: Regional lung recruitment potential during pneumoperitoneum depends on rib cage elastance, reinforcing the concept of PEEP individualization according to the patient's condition.

The Role of Multidetector Computed Tomography and the Forced Oscillation Technique in Assessing Lung Damage in Adults With Cystic Fibrosis.

BACKGROUND: With increased survival rates and the consequent emergence of an adult population with cystic fibrosis (CF), developing novel tools for periodic evaluations of these patients has become a new challenge. Thus, we sought to determine the contribution of lung-volume quantification using multidetector computed tomography (CT) in adults with CF and to investigate the association between structural changes and functional abnormalities. METHODS: This was a cross-sectional study in which 21 adults with CF and 22 control subjects underwent lung-volume quantification using multidetector CT. Voxel densities were divided into 4 bands: -1,000 to -900 Hounsfield units (HU) (hyperaerated region), -900 to -500 HU (normally aerated region), -500 to -100 HU (poorly aerated region), and -100 to 100 HU (non-aerated region). In addition, all participants performed pulmonary function tests including spirometry, body plethysmography, diffusion capacity for carbon monoxide, and the forced oscillation technique. RESULTS: Adults with CF had more non-aerated regions and poorly aerated regions with lung-volume quantification using multidetector CT than controls. Despite these abnormalities, total lung volume measured by lung-volume quantification using multidetector CT did not differ between subjects and controls. Total lung capacity (TLC) measured by body plethysmography correlated with both total lung volume (rs = 0.71, P < .001) and total air volume (rs = 0.71, P < .001) as measured with lung-volume quantification using multidetector CT. While the hyperaerated regions correlated with the functional markers of gas retention in the lungs (increased residual volume (RV) and RV/TLC ratio), the poorly aerated regions correlated with the resistive parameters measured by the forced oscillation technique (increased intercept resistance and mean resistance). We also observed a correlation between normally aerated regions and highest pulmonary diffusion values (rs = 0.68, P < .001). CONCLUSIONS: In adults with CF, lung-volume quantification using multidetector CT can destimate the lung volumes of compartments with different densities and determine the aerated and non-aerated contents of the lungs; furthermore, lung-volume quantification using multidetector CT is clearly related to pulmonary function parameters.

Integrin αDß2 (CD11d/CD18) mediates experimental malaria-associated acute respiratory distress syndrome (MA-ARDS).

BACKGROUND: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a potentially lethal complication of clinical malaria. Acute lung injury in MA-ARDS shares features with ARDS triggered by other causes, including alveolar inflammation and increased alveolar-capillary permeability, leading to leak of protein-rich pulmonary oedema fluid. Mechanisms and physiologic alterations in MA-ARDS can be examined in murine models of this syndrome. Integrin αDß2 is a member of the leukocyte, or ß2 (CD18), sub-family of integrins, and emerging observations indicate that it has important activities in leukocyte adhesion, accumulation and signalling. The goal was to perform analysis of the lungs of mice wild type C57Bl/6 (a D (+/+) ) and Knockout C57Bl/6 (a D (-/-) ) with malaria-associated acute lung injury to better determine the relevancy of the murine models and investigate the mechanism of disease. METHODS: C57BL/6 wild type (a D (+/+) ) and deficient for CD11d sub-unit (a D (-/-) ) mice were monitored after infection with 10(5) Plasmodium berghei ANKA. CD11d subunit expression RNA was measured by real-time polymerase chain reaction, vascular barrier integrity by Evans blue dye (EBD) exclusion and cytokines by ELISA. Protein and leukocytes were measured in bronchoalveolar lavage fluid (BALF) samples. Tissue cellularity was measured by the point-counting technique, F4/80 and VCAM-1 expression by immunohistochemistry. Respiratory function was analysed by non-invasive BUXCO and mechanical ventilation. RESULTS: Alveolar inflammation, vascular and interstitial accumulation of monocytes and macrophages, and disrupted alveolar-capillary barrier function with exudation of protein-rich pulmonary oedema fluid were present in P. berghei-infected wild type mice and were improved in αDß2-deficient animals. Key pro-inflammatory cytokines were also decreased in lung tissue from α D (-/-) mice, providing a mechanistic explanation for reduced alveolar-capillary inflammation and leak. CONCLUSIONS: The results indicate that αDß2 is an important inflammatory effector molecule in P. berghei-induced MA-ARDS, and that leukocyte integrins regulate critical inflammatory and pathophysiologic events in this model of complicated malaria. Genetic deletion of integrin subunit αD in mice, leading to deficiency of integrin αDß2, alters lung inflammation and acute lung injury in a mouse model of MA-ARDS caused by P. berghei.

Does acute exposure to aldehydes impair pulmonary function and structure?

Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1ß, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.

CT pulmonary densitovolumetry in patients with acromegaly: a comparison between active disease and controlled disease.

OBJECTIVE: Our purpose was to compare the findings of CT pulmonary densitovolumetry and pulmonary function in patients with active acromegaly and controlled acromegaly and, secondarily, to correlate these findings. METHODS: 11 patients with active acromegaly, 18 patients with controlled acromegaly and 17 control subjects, all non-smokers, underwent quantification of lung volume using multidetector CT (Q-MDCT) and pulmonary function tests. RESULTS: Patients with active acromegaly had larger total lung mass (TLM) values than the controls and larger amounts of non-aerated compartments than the other two groups. Patients with active acromegaly also had larger amounts of poorly aerated compartments than the other two groups, a difference that was observed in both total lung volume (TLV) and TLM. TLV as measured by inspiratory Q-MDCT correlated significantly with total lung capacity, whereas TLV measured using expiratory Q-MDCT correlated significantly with functional residual capacity. CONCLUSION: Patients with active acromegaly have more lung mass and larger amounts of non-aerated and poorly aerated compartments. There is a relationship between the findings of CT pulmonary densitovolumetry and pulmonary function test parameters. ADVANCES IN KNOWLEDGE: Although the nature of our results demands further investigation, our data suggest that both CT pulmonary densitovolumetry and pulmonary function tests can be used as useful tools for patients with acromegaly by assisting in the prediction of disease activity.

Repeated intranasal exposure to microcystin-LR affects lungs but not nasal epithelium in mice.

Microcystin-LR (MC-LR) is a harmful cyanotoxin able to induce adverse outcomes in the respiratory system. We aimed to examine the lungs and nasal epithelium of mice following a sub-chronic exposure to MC-LR. Swiss mice were intranasally instilled with 10 µL of distilled water (CTRL, n = 10) or 6.7 ng/kg of MC-LR diluted in 10 µL of distilled water (TOX, n = 8) during 30 consecutive days. Respiratory mechanics was measured in vivo and histology measurements (morphology and inflammation) were assessed in lungs and nasal epithelium samples 24 h after the last intranasal instillation. Despite the lack of changes in the nasal epithelium, TOX mice displayed an increased amount of PMN cells in the lungs (× 10(-3)/µm(2)), higher lung static elastance (cmH2O/mL), resistive and viscoelastic/inhomogeneous pressures (cmH2O) (7.87 ± 3.78, 33.96 ± 2.64, 1.03 ± 0.12, 1.01 ± 0.08, respectively) than CTRL (5.37 ± 4.02, 26.65 ± 1.24, 0.78 ± 0.06, 0.72 ± 0.05, respectively). Overall, our findings suggest that the nasal epithelium appears more resistant than lungs in this model of MC-LR intoxication.

Positive end-expiratory pressure and variable ventilation in lung-healthy rats under general anesthesia.

OBJECTIVES: Variable ventilation (VV) seems to improve respiratory function in acute lung injury and may be combined with positive end-expiratory pressure (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized that VV in combination with moderate levels of PEEP reduce the deterioration of pulmonary function related to general anesthesia. Hence, we aimed at evaluating the alveolar stability and lung protection of the combination of VV at different PEEP levels. DESIGN: Randomized experimental study. SETTING: Animal research facility. SUBJECTS: Forty-nine male Wistar rats (200-270 g). INTERVENTIONS: Animals were ventilated during 2 hours with protective low tidal volume (VT) in volume control ventilation (VCV) or VV and PEEP adjusted at the level of minimum respiratory system elastance (Ers), obtained during a decremental PEEP trial subsequent to a recruitment maneuver, and 2 cmH2O above or below of this level. MEASUREMENTS AND MAIN RESULTS: Ers, gas exchange and hemodynamic variables were measured. Cytokines were determined in lung homogenate and plasma samples and left lung was used for histologic analysis and diffuse alveolar damage scoring. A progressive time-dependent increase in Ers was observed independent on ventilatory mode or PEEP level. Despite of that, the rate of increase of Ers and lung tissue IL-1 beta concentration were significantly lower in VV than in VCV at the level of the PEEP of minimum Ers. A significant increase in lung tissue cytokines (IL-6, IL-1 beta, CINC-1 and TNF-alpha) as well as a ventral to dorsal and cranial to caudal reduction in aeration was observed in all ventilated rats with no significant differences among groups. CONCLUSIONS: VV combined with PEEP adjusted at the level of the PEEP of minimal Ers seemed to better prevent anesthesia-induced atelectasis and might improve lung protection throughout general anesthesia.

Effects of different levels of pressure support on intra-individual breath-to-breath variability.

BACKGROUND: Evidence exists that during pressure support ventilation (PSV), the addition of an extrinsic (ie, ventilator-generated) breath-to-breath variability (BBV) of breathing pattern improves respiratory function. If BBV is beneficial per se, choosing the PS level that maximizes it could be considered a valid strategy for conventional PSV. In this study, we evaluated the effect of different PS levels on intrinsic BBV in acutely ill, mechanically ventilated subjects to determine whether a significant relationship exists between PS level and BBV magnitude. METHODS: Fourteen invasively mechanically ventilated subjects were prospectively studied. PS was adjusted at 20 cm H2O and sequentially reduced to 15, 10, and 5 cm H2O. Arterial blood gas analysis and pressure at 0.1 s after the onset of inspiration (P0.1) were measured at each PS level. Airway and esophageal pressure and air flow were continuously recorded. Peak inspiratory flow, tidal volume (VT), breathing frequency, and pressure-time product (PTP) were calculated on a breath-by-breath basis. The breathing pattern variability was assessed by the coefficient of variation of the time series of VT, peak inspiratory flow, and breathing frequency from ∼ 60 consecutive breath cycles at each PS level. A general linear model for repeated measures was applied, with PS as an independent factor. A significance level of .05 was considered. RESULTS: Despite a large inter-individual difference in all measured variables (P < .001), the coefficient of variation was as low as 30%, and no significant differences in the coefficient of variation of peak inspiratory flow, breathing frequency, and VT between PS levels were observed (P > .15). Additionally, a significant increase in P0.1, PTP, and breathing frequency (P < .01) and a reduction in VT (P < .001) were observed with PS reduction. CONCLUSIONS: Despite a significant increase in spontaneous activity with PS reduction, BBV was not influenced by the PS level and was as low as 30% for all evaluated parameters.

Tidal lung recruitment and exhaled nitric oxide during coronary artery bypass grafting in patients with and without chronic obstructive pulmonary disease.

BACKGROUND: We studied the occurrence of intraoperative tidal alveolar recruitment/derecruitment, exhaled nitric oxide (eNO), and lung dysfunction in patients with and without chronic obstructive pulmonary disease (COPD) undergoing coronary artery bypass grafting (CABG). METHODS: We performed a prospective observational physiological study at a university hospital. Respiratory mechanics, shunt, and eNO were assessed in moderate COPD patients undergoing on-pump (n = 12) and off-pump (n = 8) CABG and on-pump controls (n = 8) before sternotomy (baseline), after sternotomy and before cardiopulmonary bypass (CPB), and following CPB before and after chest closure. Respiratory system resistance (R (rs)), elastance (E (rs)), and stress index (to quantify tidal recruitment) were estimated using regression analysis. eNO was measured with chemiluminescence. RESULTS: Mechanical evidence of tidal recruitment/derecruitment (stress index <1.0) was observed in all patients, with stress index <0.8 in 29% of measurements. Rrs in on-pump COPD was larger than in controls (p < 0.05). Ers increased in controls from baseline to end of surgery (19.4 ± 5.5 to 27.0 ± 8.5 ml cm H(2)O(-1), p < 0.01), associated with increased shunt (p < 0.05). Neither Ers nor shunt increased significantly in the COPD on-pump group. eNO was comparable in the control (11.7 ± 7.0 ppb) and COPD on-pump (9.9 ± 6.8 ppb) groups at baseline, and decreased similarly by 29% at end of surgery(p < 0.05). Changes in eNO were not correlated to changes in lung function. CONCLUSIONS: Tidal recruitment/derecruitment occurs frequently during CABG and represents a risk for ventilator-associated lung injury. eNO changes are consistent with small airway injury, including that from tidal recruitment injury. However, those changes are not correlated with respiratory dysfunction. Controls have higher susceptibility to develop complete lung derecruitment.

On the crucial ventilatory setting adjustment from two- to one-lung ventilation.

Lung mechanics, histology, oxygenation and type-III procollagen (PCIII) mRNA were studied aiming to evaluate the need to readjust ventilatory pattern when going from two- to one-lung ventilation (OLV). Wistar rats were assigned to three groups: the left lung was not ventilated while the right lung received: (1) tidal volume (V(T))=5 ml/kg and positive end-expiratory pressure (PEEP)=2 cm H(2)O (V5P2), (2) V(T)=10 ml/kg and PEEP=2 cm H(2)O (V10P2), and (3) V(T)=5 ml/kg and PEEP=5 cm H(2)O (V5P5). At 1-h ventilation, V5P2 showed hypoxemia, alveolar collapse and impaired lung function. Higher PEEP minimized these changes and prevented hypoxemia. Although high V(T) prevented hypoxemia and maintained a higher specific compliance than V5P2, a morphologically inhomogeneous parenchyma and higher PCIII expression resulted. In conclusion, the association of low V(T) and an adequate PEEP level could be useful to maintain arterial oxygenation without inducing a possible inflammatory/remodeling response.

LASSBio 596 per os avoids pulmonary and hepatic inflammation induced by microcystin-LR.

Cyanobacterial blooms that generate microcystins (MCYSTs) are increasingly recognized as an important health problem in aquatic ecosystems. We have previously reported the impairment of pulmonary structure and function by microcystin-LR (MCYST-LR) exposure as well as the pulmonary improvement by intraperitoneally injected (i.p.) LASSBio 596. In the present study, we aimed to evaluate the usefulness of LASSBio 596 per os on the treatment of pulmonary and hepatic injuries induced by MCYST-LR. Swiss mice received an intraperitoneal injection of 40 µl of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 µg/kg). After 6 h the animals received either saline (TOX and CTRL groups) or LASSBio 596 (50 mg/kg, LASS group) by gavage. Eight hours after the first instillation, lung impedance (static elastance, elastic component of viscoelasticity and resistive, viscoelastic and total pressures) was determined by the end-inflation occlusion method. Left lung and liver were prepared for histology. In lung and hepatic homogenates MCYST-LR, TNF-α, IL-1ß and IL-6 were determined by ELISA. LASSBio 596 per os (LASS mice) kept all lung mechanical parameters, polymorphonuclear (PMN) cells, pro-inflammatory mediators, and alveolar collapse similar to control mice (CTRL), whereas in TOX these findings were higher than CTRL. Likewise, liver structural deterioration (hepatocytes inflammation, necrosis and steatosis) and inflammatory process (high levels of pro-inflammatory mediators) were less evident in the LASS than TOX group. LASS and CTRL did not differ in any parameters studied. In conclusion, orally administered LASSBio 596 prevented lung and hepatic inflammation and completely blocked pulmonary functional and morphological changes induced by MCYST-LR.

Effects of descending positive end-expiratory pressure on lung mechanics and aeration in healthy anaesthetized piglets.

INTRODUCTION: Atelectasis and distal airway closure are common clinical entities of general anaesthesia. These two phenomena are expected to reduce the ventilation of dependent lung regions and represent major causes of arterial oxygenation impairment in anaesthetic conditions. In the present study, the behavior of the elastance of the respiratory system (Ers), as well as the lung aeration assessed by CT-scan, was evaluated during a descendent positive end-expiratory pressure (PEEP) titration. This work sought to evaluate the potential usefulness of the Ers monitoring to set the PEEP in order to prevent tidal recruitment and hyperinflation of healthy lungs under general anaesthesia. METHODS: PEEP titration (from 16 to 0 cmH2O, with a tidal volume of 8 ml/kg) was performed, and at each PEEP, helical CT-scans were obtained during end-expiratory and end-inspiratory pauses in six healthy, anaesthetized and paralyzed piglets. The distribution of lung compartments (hyperinflated (HA), normally- (NA), poorly- (PA), and non-aerated areas (N)) was determined and the tidal re-aeration was calculated as the difference between end-expiratory and end-inspiratory PA and NA areas. Similarly, the tidal hyperinflation was obtained as the difference between end-inspiratory and end-expiratory HA. The Ers was estimated on a breath-by-breath basis from the equation of motion of the respiratory system during all PEEP titration with the least squares method. RESULTS: HA decreased throughout PEEP descent from PEEP 16 cmH2O to ZEEP (ranges from 24-62% to 1-7% at end-expiratory and from 44-73% to 4-17% at end-inspiratory pauses) whereas NA areas increased (30-66% to 72-83% at end-expiratory and from 19-48% to 73-77% at end-inspiratory pauses). From 16 to 8 cmH2O, Ers decreased with a correspondent reduction in tidal hyperinflation. A flat minimum of Ers was observed from 8 to 4 cmH2O. For PEEP below 4 cmH2O, Ers increased associated with a rise in tidal re-aeration and a flat maximum of the NA areas. CONCLUSION: In healthy piglets under a descending PEEP protocol, the PEEP at minimum Ers presented a compromise between maximizing NA areas and minimizing tidal re-aeration and hyperinflation. High levels of PEEP, greater than 8 cmH2O, reduced tidal re-aeration but enlarged hyperinflation with a concomitant decrease in normally aerated areas.