Lung inflammation induced by silica particles triggers hippocampal inflammation, synapse damage and memory impairment in mice.

BACKGROUND: Considerable evidence indicates that a signaling crosstalk between the brain and periphery plays important roles in neurological disorders, and that both acute and chronic peripheral inflammation can produce brain changes leading to cognitive impairments. Recent clinical and epidemiological studies have revealed an increased risk of cognitive impairment and dementia in individuals with impaired pulmonary function. However, the mechanistic underpinnings of this association remain unknown. Exposure to SiO2 (silica) particles triggers lung inflammation, including infiltration by peripheral immune cells and upregulation of pro-inflammatory cytokines. We here utilized a mouse model of lung silicosis to investigate the crosstalk between lung inflammation and memory. METHODS: Silicosis was induced by intratracheal administration of a single dose of 2.5 mg SiO2/kg in mice. Molecular and behavioral measurements were conducted 24 h and 15 days after silica administration. Lung and hippocampal inflammation were investigated by histological analysis and by determination of pro-inflammatory cytokines. Hippocampal synapse damage, amyloid-ß (Aß) peptide content and phosphorylation of Akt, a proxy of hippocampal insulin signaling, were investigated by Western blotting and ELISA. Memory was assessed using the open field and novel object recognition tests. RESULTS: Administration of silica induced alveolar collapse, lung infiltration by polymorphonuclear (PMN) cells, and increased lung pro-inflammatory cytokines. Lung inflammation was followed by upregulation of hippocampal pro-inflammatory cytokines, synapse damage, accumulation of the Aß peptide, and memory impairment in mice. CONCLUSION: The current study identified a crosstalk between lung and brain inflammatory responses leading to hippocampal synapse damage and memory impairment after exposure to a single low dose of silica in mice.

On some factors determining the pressure drop across tracheal tubes during high-frequency percussive ventilation: a flow-independent model.

To provide an in vitro estimation of the pressure drop across tracheal tubes (ΔPTT) in the face of given pulsatile frequencies and peak pressures (Pwork) delivered by a high-frequency percussive ventilator (HFPV) applied to a lung model. Tracheal tubes (TT) 6.5, 7.5 and 8.0 were connected to a test lung simulating the respiratory system resistive (R = 5, 20, 50 cmH2O/L/s) and elastic (C = 10, 20, and 50 mL/cmH2O) loads. The model was ventilated by HFPV with a pulse inspiratory peak pressure (work pressure Pwork) augmented in 5-cmH2O steps from 20 to 45 cmH2O, yielding 6 diverse airflows. The percussive frequency (f) was set to 300, 500 and 700 cycles/min, respectively. Pressure (Paw and Ptr) and flow (V') measurements were performed for all 162 possible combinations of loads, frequencies, and work pressures for each TT size, thus yielding 486 determinations. For each respiratory cycle ΔPTT was calculated by subtracting each peak Ptr from its corresponding peak Paw. A non-linear model was constructed to assess the relationships between single parameters. Performance of the produced model was measured in terms of root mean square error (RMSE) and the coefficient of determination (r2). ΔPTT was predicted by Pwork (exponential Gaussian relationship), resistance (quadratic and linear terms), frequency (quadratic and linear terms) and tube diameter (linear term), but not by compliance. RMSE of the model on the testing dataset was 1.17 cmH2O, r2 was 0.79 and estimation error was lower than 1 cmH2O in 68% of cases. As a result, even without a flow value, the physician would be able to evaluate ΔPTT pressure. If the present results of our bench study could be clinically confirmed, the use of a nonconventional ventilatory strategy as HFPV, would be safer and easier.

FLOW-i ventilator performance in the presence of a circle system leak.

Recently, the FLOW-i anaesthesia ventilator was developed based on the SERVO-i intensive care ventilator. The aim of this study was to test the FLOW-i's tidal volume delivery in the presence of a leak in the breathing circuit. We ventilated a test lung model in volume-, pressure-, and pressure-regulated volume-controlled modes (VC, PC, and PRVC, respectively) with a FLOW-i. First, the circuit remained airtight and the ventilator was tested with fresh gas flows of 6, 1, and 0.3 L/min in VC, PC, and PRVC modes and facing 4 combinations of different resistive and elastic loads. Second, a fixed leak in the breathing circuit was introduced and the measurements repeated. In the airtight system, FLOW-i maintained tidal volume (VT) and circuit pressure at approximately the set values, independently of respiratory mode, load, or fresh gas flow. In the leaking circuit, set VT = 500 mL, FLOW-i delivered higher VTs in PC (about 460 mL) than in VC and PRVC, where VTs were substantially less than 500 mL. Interestingly, VT did not differ appreciably from 6 to 0.3 L/min of fresh air flow among the 3 ventilatory modes. In the absence of leakage, peak inspiratory pressures were similar, while they were 35-45 % smaller in PRVC and VC than in PC mode in the presence of leaks. In conclusion, FLOW-i maintained VT (down to fresh gas flows of 0.3 L/min) to 90 % of its preset value in PC mode, which was 4-5 times greater than in VC or PRVC modes.

Spontaneous effort causes occult pendelluft during mechanical ventilation.

RATIONALE: In normal lungs, local changes in pleural pressure (P(pl)) are generalized over the whole pleural surface. However, in a patient with injured lungs, we observed (using electrical impedance tomography) a pendelluft phenomenon (movement of air within the lung from nondependent to dependent regions without change in tidal volume) that was caused by spontaneous breathing during mechanical ventilation. OBJECTIVES: To test the hypotheses that in injured lungs negative P(pl) generated by diaphragm contraction has localized effects (in dependent regions) that are not uniformly transmitted, and that such localized changes in P(pl) cause pendelluft. METHODS: We used electrical impedance tomography and dynamic computed tomography (CT) to analyze regional inflation in anesthetized pigs with lung injury. Changes in local P(pl) were measured in nondependent versus dependent regions using intrabronchial balloon catheters. The airway pressure needed to achieve comparable dependent lung inflation during paralysis versus spontaneous breathing was estimated. MEASUREMENTS AND MAIN RESULTS: In all animals, spontaneous breathing caused pendelluft during early inflation, which was associated with more negative local P(pl) in dependent regions versus nondependent regions (-13.0 ± 4.0 vs. -6.4 ± 3.8 cm H2O; P < 0.05). Dynamic CT confirmed pendelluft, which occurred despite limitation of tidal volume to less than 6 ml/kg. Comparable inflation of dependent lung during paralysis required almost threefold greater driving pressure (and tidal volume) versus spontaneous breathing (28.0 ± 0.5 vs. 10.3 ± 0.6 cm H2O, P < 0.01; 14.8 ± 4.6 vs. 5.8 ± 1.6 ml/kg, P < 0.05). CONCLUSIONS: Spontaneous breathing effort during mechanical ventilation causes unsuspected overstretch of dependent lung during early inflation (associated with reciprocal deflation of nondependent lung). Even when not increasing tidal volume, strong spontaneous effort may potentially enhance lung damage.

End-tidal versus manually-controlled low-flow anaesthesia.

During low-flow manually-controlled anaesthesia (MCA) the anaesthetist needs constantly adjust end-tidal oxygen (EtO2) and anaesthetic concentrations (EtAA) to assure an adequate and safe anaesthesia. Recently introduced anaesthetic machines can automatically maintain those variables at target values, avoiding the burden on the anaesthetist. End-tidal-controlled anaesthesia (EtCA) and MCA provided by the same anaesthetic machine under the same fresh gas flow were compared. Eighty patients were prospectively observed: in MCA group (n = 40) target end-tidal sevoflurane (1%) and EtO2 concentrations (≥ 35%) were manually controlled by the anaesthetist. In EtCA group (n = 40) the same anaesthetic machine with an additional end-tidal control feature was used to reach the same targets, rendering automatic the achievement and maintenance of those targets. Anaesthetic machine characteristics, amount of consumed gases, oxygen and sevoflurane efficiencies, and the amount of interventions by the anaesthetist were recorded. In EtCA group EtAA was achieved later (145 s) than in MCA (71 s) and remained controlled thereafter. Even though the target expired gas fractions were achieved faster in MCA, manual adjustments were required throughout anaesthesia for both oxygen and sevoflurane. In MCA patients the number of manual adjustments to stabilize EtAA and EtO2 were 137 and 107, respectively; no adjustment was required in EtCA. Low-flow anaesthesia delivered with an anaesthetic machine able to automatically control EtAA and EtO2 provided the same clinical stability and avoided the continuous manual adjustment of delivered sevoflurane and oxygen concentrations. Hence, the anaesthetist could dedicate more time to the patient and operating room activities.

Volume-independent elastance: a useful parameter for open-lung positive end-expiratory pressure adjustment.

BACKGROUND: A decremental positive end-expiratory pressure (PEEP) trial after full lung recruitment allows for the adjustment of the lowest PEEP that prevents end-expiratory collapse (open-lung PEEP). For a tidal volume (Vt) approaching zero, the PEEP of minimum respiratory system elastance (PEEP(minErs)) is theoretically equal to the pressure at the mathematical inflection point (MIP) of the pressure-volume curve, and seems to correspond to the open-lung PEEP in a decremental PEEP trial. Nevertheless, the PEEP(minErs) is dependent on Vt and decreases as Vt increases. To circumvent this dependency, we proposed the use of a second-order model in which the volume-independent elastance (E1) is used to set open-lung PEEP. METHODS: Pressure-volume curves and a recruitment maneuver followed by decremental PEEP trials, with a Vt of 6 and 12 mL/kg, were performed in 24 Wistar rats with acute lung injury induced by intraperitoneally injected (n = 8) or intratracheally instilled (n = 8) Escherichia coli lipopolysaccharide. In 8 control animals, the anterior chest wall was surgically removed after PEEP trials, and the protocol was repeated. Airway pressure (Paw) and flow (F) were continuously acquired and fitted by the linear single-compartment model (Paw = Rrs·F + Ers·V + PEEP, where Rrs is the resistance of the respiratory system, and V is volume) and the volume-dependent elastance model (Paw = Rrs·F + E1 + E2·V·V + PEEP, where E2·V is the volume-dependent elastance). From each model, PEEPs of minimum Ers and E1 (PEEP(minE1)) were identified and compared with each respective MIP. The accuracy of PEEPminE1 and PEEPminErs in estimating MIP was assessed by bias and precision plots. Comparisons among groups were performed with the unpaired t test whereas a paired t test was used between the control group before and after chest wall removal and within groups at different Vts. All P values were then corrected for multiple comparisons by the Bonferroni procedure. RESULTS: In all experimental groups, PEEPminErs, but not PEEPminE1, tended to decrease as Vt increased. The difference between MIP and PEEPminE1 exhibited a lower bias compared with the difference between MIP and PEEPminErs (P < 0.001). The PEEPminE1 was always significantly higher than the PEEPminErs (7.7 vs 3.8, P < 0.001) and better approached MIP (7.7 vs 7.3 cm H2O with P = 0.04 at low Vt, and 7.8 vs 7.1 cm H2O with P < 0.001 at high Vt). CONCLUSIONS: PEEPminE1 better identifies the open-lung PEEP independently of the adjusted Vt, and may be a practical, more individualized approach for PEEP titration.

Early short-term application of high-frequency percussive ventilation improves gas exchange in hypoxemic patients.

BACKGROUND: Hypoxemia in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients represents a common finding in the intensive care unit (ICU) and frequently does not respond to standard ventilatory techniques. OBJECTIVE: To study whether the early short-term application of high-frequency percussive ventilation (HFPV) can improve gas exchange in hypoxemic patients with ALI/ARDS or many other conditions in comparison to conventional ventilation (CV) using the same mean airway pressure (P(aw)), representing the main determinant of oxygenation and hemodynamics, irrespective of the mode of ventilation. METHODS: Thirty-five patients not responding to CV were studied. During the first 12 h after admission to the ICU the patients underwent CV. Thereafter HFPV was applied for 12 h with P(aw) kept constant. They were then returned to CV. Gas exchange was measured at: 12 h after admission, every 4 h during the HFPV trial, 1 h after the end of HFPV, and 12 h after HFPV. Thirty-five matched patients ventilated with CV served as the control group (CTRL). RESULTS: PaO(2)/FiO(2) and the arterial alveolar ratio (a/A PO(2)) increased during HFPV treatment and a PaO(2)/FiO(2) steady state was reached during the last 12 h of CV, whereas both did not change in CTRL. PaCO(2) decreased during the first 4 h of HFPV, but thereafter it remained unaltered; PaCO(2) did not vary in CTRL. Respiratory system compliance increased after HFPV. CONCLUSIONS: HFPV improved gas exchange in patients who did not respond to conventional treatment. This improvement remained unaltered until 12 h after the end of HFPV.

Comparison of noninvasive ventilation by sequential use of mask and helmet versus mask in acute exacerbation of chronic obstructive pulmonary disease: a preliminary study.

BACKGROUND: Noninvasive positive pressure ventilation (NPPV) using a face mask is the ventilatory mode of choice in selected patients experiencing acute exacerbation of chronic obstructive pulmonary disease (COPD). A high incidence of intolerance limits the use of this approach. OBJECTIVE: To evaluate the sequential use of mask and helmet during NPPV in patients with severe exacerbation of COPD in order to reduce the intolerance to these devices. METHODS: Fifty-three patients ventilated for the first 2 h with NPPV by mask were studied. If gas exchange and clinical status improved, they were randomized to continue on NPPV by mask or helmet. Physiological parameters were measured at admission, after the first 2 h on NPPV by mask, 4 h after randomization and at discharge. Need for intubation, ventilatory assistance, length of stay (LOS) and complications were recorded. RESULTS: After the first 2 h of NPPV, gas exchange and clinical parameters improved in 40 patients. Four hours after randomization, PaCO(2) was lower in the mask group than in the helmet group. Nine patients in the mask group and 2 in the helmet group failed NPPV, 8 and 1, respectively, owing to intolerance. Time of noninvasive ventilation and LOS were lower in the mask than in the helmet group. CONCLUSIONS: In patients with acute exacerbation of COPD and undergoing NPPV, the sequential use of a mask and helmet diminished the incidence of failure. Under the present experimental conditions, the use of a helmet increased LOS and the duration of artificial ventilation.

Panic disorder respiratory subtype: psychopathology and challenge tests - an update.

Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.

High-frequency percussive ventilation improves perioperatively clinical evolution in pulmonary resection.

OBJECTIVE: During thoracotomy, positive end-expiratory pressure is applied to the dependent lung and continuous positive airway pressure (CPAP) inflates the nondependent lung to avoid hypoxemia. These methods do not allow the removal of produced secretions. We hypothesized that high-frequency percussive ventilation(HFPV) can improve both conditions and reduce hospital length of stay in these patients. DESIGN: Randomized prospective study. SETTING: University Hospital. PATIENTS: Fifty-three consecutive patients undergoing elective pulmonary partial resection were enrolled. Nine were excluded because of surgical reasons. INTERVENTIONS: The nondependent lung was ventilated with HFPV in 22 patients and other 22 received CPAP. In both groups,the dependent lung was ventilated with continuous mechanical ventilation. MEASUREMENT AND MAIN RESULTS: Cardiocirculatory variables and blood gas analysis were measured during surgery. Postoperatively,all patients underwent chest physiotherapy, and SpO2,body temperature, the amount of sputum produced, and chest radiography were recorded. Before nondependent lung re-expansion,HFPV patients presented higher PaO2 than CPAP group (p = 0.020). The amount of secretions was higher in chronic obstructive pulmonary disease patients treated with HFPV than in those who received CPAP (199 and 64 mL, respectively, p = 0.028). HFPV increased by 5.28 times the chance of sputum production by chronic obstructive pulmonary disease patients (chi(2) = 46.66, p < 0.0001; odds ratio = 5.28). A patient treated with HFPV had a 3.14-fold larger chance of being discharged earlier than a CPAP-treated subject (likelihood ratio = 11.5, p = 0.0007). CONCLUSIONS: Under the present settings, HFPV improved oxygenation in one-lung ventilation during pulmonary resection. Postoperatively, it decreased the length of stay and increased the removal of secretions in comparison with CPAP.

Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury.

OBJECTIVE: To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). DESIGN: Prospective, randomized, and controlled experimental study. SETTING: University research laboratory. SUBJECTS: Wistar rats were randomly assigned to control (C) [saline (0.1 mL), intraperitoneally] and ALI [paraquat (15 mg/kg), intraperitoneally] groups. MEASUREMENTS AND MAIN RESULTS: After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H2O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (DeltaP2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and DeltaP2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. CONCLUSIONS: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and DeltaP2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful.

Panic disorder and social anxiety disorder subtypes in a caffeine challenge test.

Studies have demonstrated the vulnerability of anxiety disorder patients to challenge tests. Our aim was to observe if panic disorder (PD) patients and generalized social anxiety disorder (GSAD) and performance social anxiety disorder (PSAD) patients respond in a similar way to the induction of anxiety symptoms and panic attacks by an oral caffeine challenge test. We compared 28 PD patients, 25 GSAD patients, 19 PSAD, and 26 control subjects after a 480-mg caffeine test. The patients had not received psychotropic drugs for at least a 4-week period. In a randomized double-blind experiment performed in two occasions 7 days apart, 480 mg of caffeine and a caffeine-free solution were administered and anxiety scales were administered before and after each test. A panic attack was induced in 17 (60.7%) PD patients, 4 (16.0%) GSAD patients, and 10 (52.6%) PSAD patients, during the caffeine test. None of the control subjects had a panic attack after the caffeine intake. Neither patients nor any control subject had a panic attack after drinking the caffeine-free solution. Our data suggest that there is an association between PD and PSAD hyperreactivity to an oral caffeine challenge test. The PD and PSAD patients had a higher number of induced panic attacks, some specific anxiety symptoms, and a more severe anxiety response than GSAD patients and normal volunteers.

The anti-inflammatory and anti-oxidative actions of eugenol improve lipopolysaccharide-induced lung injury.

Acute lung injury (ALI) remains a major cause of mortality. In lipopolysaccharide (LPS)-stimulated macrophages, eugenol reduces cyclooxygenase-2 expression, NF-κB activation, and inflammatory mediators. We examined the anti-inflammatory and anti-oxidative action of eugenol in an in vivo model of LPS-induced lung injury. Lung mechanics and histology were analyzed in mice 24 h after LPS exposure, with and without eugenol treatment at different doses. Additional animals, submited to the same protocol, were treated with eugenol at 150 mg/kg to determine its effect on inflammatory cytokines (ELISA) and oxidative markers. LPS-induced lung functional and histological changes were significantly improved by eugenol, in a dose-dependent way. Furthermore, eugenol (150 mg/kg) was able to inhibit the release of inflammatory cytokines (TNF-α, IL-1ß and IL-6), NADPH oxidase activity, as well as antioxidant enzymes activity (superoxide dismutase, catalase and glutathione peroxidase). Finally, eugenol reduced LPS-induced protein oxidation. In conclusion, eugenol improved in vivo LPS-induced ALI through both anti-inflammatory and anti-oxidative effects, avoiding damage to lung structure.

Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit.

OBJECTIVE: To test the effects of positive expiratory pressure on the leakage of fluid around cuffs of different tracheal tubes, in mechanically ventilated patients and in a benchtop model. DESIGN: Randomized clinical trial and experimental in vitro study. SETTING: Intensive care unit of a university hospital. PATIENTS: Forty patients recovering in the intensive care unit were ventilated in volume-controlled mode. Twenty patients were randomly intubated with Hi-Lo tubes (HL group), whereas the remaining 20 subjects were intubated with SealGuard tubes (SG group). INTERVENTIONS: Immediately after intubation and cuff inflation with 30 cm H2O, Evans blue was applied onto the cephalic surface of the tracheal tube cuff. A 5-cm H2O positive expiratory pressure was used during the first 5 hrs of stay, and thereafter it was removed. Bronchoscopy verified whether the dye leaked around the cuff. The experiment lasted 12 hrs. Leakage was also tested in vitro with the same tracheal tubes with incremental level of positive expiratory pressure. MEASUREMENTS AND MAIN RESULTS: At 1 hr, 5 hrs, and thereafter hourly until 12 hrs, bronchoscopy was used to test the presence of dye on the trachea caudal to the cuff. At the fifth hour, two patients of the HL group failed the test. One hour after positive expiratory pressure removal, all subjects in group HL exhibited a dyed lower trachea. On the other hand, one patient in group SG presented a leak at the eighth hour, and at the 12th hour three of them were still sealed. In vitro, the same level of positive expiratory pressure delayed the passage of dye around the cuff; after 30 mins positive expiratory pressure was removed, and in 10 mins all dye leaked only in the Hi-Lo tube. CONCLUSIONS: We found that 5 cm H2O positive expiratory pressure was effective in delaying the passage of fluid around the cuffs of tracheal tubes both in vivo and in vitro. The SealGuard tube proved to be more resistant to leakage than Hi-Lo.

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 microg, 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: PaO2, 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.

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

OBJECTIVE: Corticosteroids 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, Cexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 microg, ALIp) or intraperitoneally (125 microg, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp 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 static elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interleukin-6, and transforming growth factor (TGF)-beta levels in bronchoalveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta1 and TGF-beta2 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, IFNgamma, and TGF-beta2 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.

A caffeine challenge test in panic disorder patients, their healthy first-degree relatives, and healthy controls.

Our aim was to observe the induction of anxiety symptoms and panic attacks by a caffeine challenge test in panic disorder (PD) patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 PD patients, 27 healthy first-degree relatives of probands with PD, and 22 healthy volunteers with no family history of PD. In a randomized double-blind experiment performed over two occasions 7 days apart, 480 mg caffeine and a caffeine-free solution were administered in a coffee form. Using specific panic attack criteria, 52.0% (n=13) PD patients, 40.7% (n=11) first-degree relatives (chi2=1.81, df=1, P=0.179), and none of the control subjects had a panic attack after the test (chi2=51.7, df=2, P<0.001). In this caffeine challenge test, PD patients and their first-degree relatives were more sensitive than healthy volunteers to the panic attack symptoms but less sensitive to headache, increase in blood pressure, and insomnia. Our data suggest that there is an association between panic attacks after the intake of 480 mg of caffeine in PD patients and their first-degree relatives. There is a clear differentiation of PD patients and their first-degree relatives by a caffeine test from the healthy group.

Impact of lung remodelling on respiratory mechanics in a model of severe allergic inflammation.

We developed a model of severe allergic inflammation and investigated the impact of airway and lung parenchyma remodelling on in vivo and in vitro respiratory mechanics. BALB/c mice were sensitized and challenged with ovalbumin in severe allergic inflammation (SA) group. The control group (C) received saline using the same protocol. Light and electron microscopy showed eosinophil and neutrophil infiltration and fibrosis in airway and lung parenchyma, mucus gland hyperplasia, and airway smooth muscle hypertrophy and hyperplasia in SA group. These morphological changes led to in vivo (resistive and viscoelastic pressures, and static elastance) and in vitro (tissue elastance and resistance) lung mechanical alterations. Airway responsiveness to methacholine was markedly enhanced in SA as compared with C group. Additionally, IL-4, IL-5, and IL-13 levels in the bronchoalveolar lavage fluid were higher in SA group. In conclusion, this model of severe allergic lung inflammation enabled us to directly assess the role of airway and lung parenchyma inflammation and remodelling on respiratory mechanics.

Effects of amiodarone on lung tissue mechanics and parenchyma remodeling.

We studied the results of chronic oral administration of amiodarone on in vitro lung tissue mechanics, light and electron microscopy. Fifteen Wistar male rats were divided into three groups. In control (CTRL) group animals received saline (0.5 mL/day). In amiodarone (AMIO) groups, amiodarone was administered by gavage at a dose of 175 mg/kg 5 days per week for 6 (6AMIO) or 12 weeks (12AMIO). Lung tissue strips were analyzed 24h after the last drug administration. Tissue resistance and elastance were higher in 6AMIO and 12AMIO than in CTRL, while hysteresivity was similar in all groups. Total amount of collagen fibers in lung parenchyma increased progressively with the time course of the lesion. However, at 6 weeks there was an increase in the amount of type III collagen fibers, while in 12AMIO mainly type I collagen fibers were found. In our study amiodarone increased lung tissue impedance that was accompanied by matrix remodeling and lesion of type II pneumocytes.

Effects of different nutritional support on lung mechanics and remodelling in undernourished rats.

This study investigated the impact of three different oral nutritional support regimens on lung mechanics and remodelling in young undernourished Wistar rats. In the nutritionally deprived group, rats received one-third of their usual daily food consumption for 4 weeks. Undernourished rats were divided into three groups receiving a balanced, glutamine-supplemented, or long-chain triglyceride-supplemented diet for 4 weeks. In the two control groups, rats received food ad libitum for 4 (C4) or 8 weeks. Lung viscoelastic pressure and static elastance were higher in undernourished compared to C4 rats. After refeeding, lung mechanical data remained altered except for the glutamine-supplemented group. Undernutrition led to a reduced amount of elastic and collagen fibres in the alveolar septa. Elastic fibre content returned to control with balanced and glutamine-supplemented diets, but increased with long-chain triglyceride-supplemented diet. The amount of collagen fibre augmented independent of nutritional support. In conclusion, glutamine-supplemented diet is better at reducing morphofunctional changes than other diets after 4 weeks of refeeding.