Mild Lung Injury Research Articles

The Comparison of Spontaneous Breathing and Muscle Paralysis in Two Different Severities of Experimental Lung Injury*

The benefits of spontaneous breathing over muscle paralysis have been proven mainly in mild lung injury; no one has yet evaluated the effects of spontaneous breathing in severe lung injury. We investigated the effects of spontaneous breathing in two different severities of lung injury compared with muscle paralysis. Prospective, randomized, animal study. University animal research laboratory. Twenty-eight New Zealand white rabbits. Rabbits were randomly divided into the mild lung injury (surfactant depletion) group or severe lung injury (surfactant depletion followed by injurious mechanical ventilation) group and ventilated with 4-hr low tidal volume ventilation with spontaneous breathing or without spontaneous breathing (prevented by a neuromuscular blocking agent). Inspiratory pressure was adjusted to control tidal volume to 5-7 mL/kg, maintaining a plateau pressure less than 30 cm H2O. Dynamic CT was used to evaluate changes in lung aeration and the regional distribution of tidal volume. In mild lung injury, spontaneous breathing improved oxygenation and lung aeration by redistribution of tidal volume to dependent lung regions. However, in severe lung injury, spontaneous breathing caused a significant increase in atelectasis with cyclic collapse. Because of the severity of lung injury, this group had higher plateau pressure and more excessive spontaneous breathing effort, resulting in the highest transpulmonary pressure and the highest driving pressure. Although no improvements in lung aeration were observed, muscle paralysis with severe lung injury resulted in better oxygenation, more even tidal ventilation, and less histological lung injury. In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.

Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology

IntroductionBiphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assistance has not been determined. Furthermore, it is unclear whether the effects of partial ventilatory support depend on acute lung injury (ALI) etiology. This study aimed to investigate the impact of spontaneous and time-cycled control breaths during BIVENT on the lung and diaphragm in experimental pulmonary (p) and extrapulmonary (exp) ALI.MethodsThis was a prospective, randomized, controlled experimental study of 60 adult male Wistar rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALIp) or intraperitoneally (ALIexp). After 24 hours, animals were anesthetized and further randomized as follows: (1) pressure-controlled ventilation (PCV) with tidal volume (Vt) = 6 ml/kg, respiratory rate = 100 breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75, and 50 breaths/min). BIVENT was set with two levels of CPAP (Phigh = 10 cmH2O and Plow = 5 cmH2O). Inspiratory time was kept constant (Thigh = 0.3 s).ResultsBIVENT was associated with reduced markers of inflammation, apoptosis, fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both ALI models when compared to PCV. The inspiratory effort during spontaneous breaths increased during BIVENT-50 in both ALI models. In ALIp, alveolar collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and diaphragmatic injury was lower during BIVENT-50 compared to PCV and BIVENT-100. In ALIexp, alveolar collapse during BIVENT-100 and BIVENT-75 was comparable to PCV, while decreasing with BIVENT-50, and diaphragmatic injury increased during BIVENT-50.ConclusionsIn mild ALI, BIVENT had a lower biological impact on lung tissue compared to PCV. In contrast, the response of atelectasis and diaphragmatic injury to BIVENT differed according to the rate of spontaneous/controlled breaths and ALI etiology.

Pulmonary immunopathology mediated by proteolytic processing of TNF-α by antiviral CD8+ T cells (105.11)

Abstract Infection with influenza virus evokes a potent CD8+ T cell response that may contribute to lung immunopathology. Recognition of alveolar anitgen by CD8+ T cells results in significant injury that is critically dependent on TNF-α expressed by CD8+ T cells and is largely mediated by the secretion of chemokines by alveolar epithelial cells and the subsequent pulmonary infiltration. TNF-α is expressed as a transmembrane (tm) protein that is proteolytically processed by TNF-α converting enzyme (TACE) to produce soluble (s) TNF-α. To determine the roles of tmTNF-α and sTNF-α in CD8+ T cell mediated lung injury, we generated CD8+ T cells that express either a noncleavable tmTNF-α or have a deletion in the catalytic domain of TACE. Both T cells are impaired in sTNF-α production but exhibited no defect in other effector functions. In vitro analysis indicated that proteolytic processing of tmTNF-α to sTNF-α was required to induce alveolar epithelial cell expression of macrophage inflammatory protein-2. Furthermore, inhibition of proteolytic processing of TNF-α resulted in reduced induction of alveolar epithelial cell chemokines, less neutrophil infiltration and milder lung injury, though these T cells exhibited no defect in antiviral activity in vivo. This indicates that proteolytic processing of tmTNF-α to sTNF-α is a critical event in the initiation of CD8+ T cell mediated lung injury and represents a potential mechanism of regulation of immunopathology during an influenza infection.

Evaluation of lung injury and respiratory mechanics in a rat model of acute pancreatitis complicated with endotoxin

BackgroundAcute lung injury (ALI) is a common complication of acute pancreatitis (AP) and contributes to the majority of AP-associated deaths, particularly in the setting of secondary infection. This ‘two-hit’ model mimics clinical cases where the presentation of AP is associated with mild lung injury that, following a secondary direct lung infection, can result in respiratory dysfunction and death. We therefore aimed to characterize lung injury in a clinically-relevant ‘two-hit’ rat model of caerulein-induced AP combined with intratracheal endotoxin. MethodsRats received 7 hourly intraperitoneal injections of caerulein (50μg/kg). Twenty four hours following the first caerulein injection, rats were anaesthetised and LPS (15mg/kg) was instilled intratracheally. Following LPS instillation, rats were ventilated for a total of 2h. ResultsIn the present study, AP results in mild pulmonary injury indicated by increased lung myeloperoxidase (MPO) activity and edema, but with no alteration of respiratory function, while intratracheal instillation of LPS results in more substantial pulmonary injury. The induction of AP challenged with secondary intratracheal LPS results in an exacerbation of lung damage indicated by further increased lung edema, plasma and bronchoalveolar (BAL) CINC-1 concentration, lung damage histology score, and lung tissue resistance and elastance, compared with LPS alone. ConclusionsIn conclusion, the addition of instilled LPS acted as a “second-hit” and exacerbated caerulein-induced AP, compared with the induction of AP alone or the instillation of LPS alone. Given its clinical relevance, this model could prove useful for examination of therapeutic interventions for ALI following secondary infection.

Preparation and characterization of lung-targeting ceftiofur-loaded gelatin microspheres

Background: Ceftiofur is an effective antibiotic against respiratory infections in livestock. However, ceftiofur concentration that is found in lungs after intravenous injection is not effective. Fortunately, ceftiofur-loaded gelatin microsphere (Cef-MS) enjoys advantages of lung-targeting and can achieve an effective concentration. However, no study has been reported on this modality of drug delivery.Objective: We investigated the properties of this delivery modality—lung targeting ceftiofur-Cef-MSs.Methods: We prepared Cef-MS and investigated drug loading, stability and release characteristics in vitro and studied tissue distribution patterns and potential lung injury in mice.Results: Results showed that the average size and span value are 21.26 μm and 1.07, respectively. Drug loading and loading efficiency were 15.31 and 76.55%, respectively. Cef-MSs were stable in light, heat and humidity, except that agglutinative phenomenon was observed in 90% humidity after 10 days. Cef-MS presented a slower in vitro release pattern compared to ceftiofur. Cef-MS mainly concentrates in lungs after intravenous administration. Furthermore, histopathological studies showed that Cef-MS only induces mild and reversible lung injury and is biologically safe.Conclusion: Cef-MS is a promising alternative form with high lung-targeting properties for the treatment of respiratory infections.

Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury

Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury

Spontaneous breathing during high‐frequency oscillatory ventilation improves regional lung characteristics in experimental lung injury

Maintenance of spontaneous breathing is advocated in mechanical ventilation. This study evaluates the effect of spontaneous breathing on regional lung characteristics during high-frequency oscillatory (HFO) ventilation in an animal model of mild lung injury. Lung injury was induced by lavage with normal saline in eight pigs (weight range 47-64 kg). HFO ventilation was applied, in runs of 30 min on paralyzed animals or on spontaneous breathing animals with a continuous fresh gas flow (CF) or a custom-made demand flow (DF) system. Electrical impedance tomography (EIT) was used to assess lung aeration and ventilation and the occurrence of hyperinflation. End expiratory lung volume (EELV) decreased in all different HFO modalities. HFO, with spontaneous breathing maintained, showed preservation in lung volume in the dependent lung regions compared with paralyzed conditions. Comparing DF with paralyzed conditions, the center of ventilation was located at 50% and 51% (median, left and right lung) from anterior to posterior and at 45% and 46% respectively, P<0.05. Polynomial coefficients using a continuous flow were -0.02 (range -0.35 to 0.32) and -0.01 (-0.17 to 0.23) for CF and DF, respectively, P=0.01. This animal study demonstrates that spontaneous breathing during HFO ventilation preserves lung volume, and when combined with DF, improves ventilation of the dependent lung areas. No significant hyperinflation occurred on account of spontaneous breathing. These results underline the importance of maintaining spontaneous breathing during HFO ventilation and support efforts to optimize HFO ventilators to facilitate patients' spontaneous breathing.

Alveolar but Not Intravenous S-Ketamine Inhibits Alveolar Sodium Transport and Lung Fluid Clearance in Rats

S-ketamine is frequently used for analgosedation, especially during sepsis and cardiovascular instability. Because S-ketamine blocks voltage-gated sodium (Na+) channels in neurons and skeletal muscle, it is conceivable that S-ketamine also blocks alveolar epithelial Na+ channels that are crucial for alveolar fluid clearance (AFC). We studied the effects of alveolar and IV S-ketamine on transalveolar Na+ transport and AFC, and investigated whether IV S-ketamine enters the alveolar space in response to endotoxemia-induced pulmonary inflammation. Cultured rat alveolar type II (ATII) cells were exposed to S-ketamine and/or the Na+ channel blocker amiloride (100 microM) and transepithelial transport indicated by short circuit current (ISC) was measured in Ussing chambers. AFC was measured in fluid-instilled lungs of anesthetized rats with or without amiloride added to the instillate. S-ketamine was either added to the instillate or injected IV. To induce mild lung injury that might favor the appearance of IV S-ketamine at the alveolar surface, endotoxemia was induced by IV lipopolysaccharide (7.5 mg/kg). In ATII cells, S-ketamine (25 microg/mL) caused a decrease of ISC regardless of apical (-18.9%+/- 1.4%; P < 0.001) or basolateral (-20.4% +/- 3.7%; P < 0.001) application. In ATII cells pretreated with amiloride, addition of apical or basolateral S-ketamine did not decrease ISC. AFC was approximately 8% per 30 minutes in control rats. S-ketamine (5 microg/mL) in the instillate reduced AFC to 1.1% +/- 1.5% (P = 0.04) by decreasing amiloride-sensitive transepithelial Na+ transport. Intravenous S-ketamine (20 mg/kg) did not affect AFC (P = 0.31). In the presence of lipopolysaccharide-induced inflammation, the concentration of IV-injected S-ketamine in bronchoalveolar lavage fluid remained below the concentration that inhibited AFC. Although exposure of the rat alveolar epithelium to S-ketamine decreases amiloride-sensitive transalveolar Na+ transport and AFC, IV S-ketamine at clinically relevant bolus concentrations does not affect AFC, even in the presence of mild lung injury.

Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury

The goal of the study was to compare the effects of different assisted ventilation modes with pressure controlled ventilation (PCV) on lung histology, arterial blood gases, inflammatory and fibrogenic mediators in experimental acute lung injury (ALI). Paraquat-induced ALI rats were studied. At 24 h, animals were anaesthetised and further randomized as follows (n = 6/group): (1) pressure controlled ventilation mode (PCV) with tidal volume (V (T)) = 6 ml/kg and inspiratory to expiratory ratio (I:E) = 1:2; (2) three assisted ventilation modes: (a) assist-pressure controlled ventilation (APCV1:2) with I:E = 1:2, (b) APCV1:1 with I:E = 1:1; and (c) biphasic positive airway pressure and pressure support ventilation (BiVent + PSV), and (3) spontaneous breathing without PEEP in air. PCV, APCV1:1, and APCV1:2 were set with P (insp) = 10 cmH(2)O and PEEP = 5 cmH(2)O. BiVent + PSV was set with two levels of CPAP [inspiratory pressure (P (High) = 10 cmH(2)O) and positive end-expiratory pressure (P (Low) = 5 cmH(2)O)] and inspiratory/expiratory times: T (High) = 0.3 s and T (Low) = 0.3 s. PSV was set as follows: 2 cmH(2)O above P (High) and 7 cmH(2)O above P (Low). All rats were mechanically ventilated in air and PEEP = 5 cmH(2)O for 1 h. Assisted ventilation modes led to better functional improvement and less lung injury compared to PCV. APCV1:1 and BiVent + PSV presented similar oxygenation levels, which were higher than in APCV1:2. Bivent + PSV led to less alveolar epithelium injury and lower expression of tumour necrosis factor-alpha, interleukin-6, and type III procollagen. In this experimental ALI model, assisted ventilation modes presented greater beneficial effects on respiratory function and a reduction in lung injury compared to PCV. Among assisted ventilation modes, Bi-Vent + PSV demonstrated better functional results with less lung damage and expression of inflammatory mediators.

Alveolar Accumulation/Concentration of Nitrogen During Apneic Oxygenation With Arteriovenous Carbon Dioxide Removal

In a model of acute lung injury (ALI), previously, we have shown that apneic oxygenation, using an inspiratory O2 fraction (FiO2) of 1.0 combined with extracorporeal arteriovenous CO2 removal (AO-AVCR) maintains adequate arterial O2 and CO2 levels for a prolonged period. However, it is important that FiO2 lower than 1.0 can be used to avoid possible pulmonary oxygen toxicity. In preliminary studies, arterial oxygenation decreased to extreme low levels, when FiO2 <1 was used in apneic oxygenation. We assumed that this was caused either by alveolar accumulation/concentration of N2 or by absorption atelectasis. In four anesthetized and mechanically ventilated pigs, mild lung injury was induced. After a lung recruitment maneuver, we initiated two 20-minute periods of AO-AVCR with FiO2 of 1 and 0.5, respectively. By using FiO2 = 1, PaO2 remained above 300 mm Hg. At the end of the period, the alveolar O2 fraction (FAO2) was 0.89 (0.88-0.89; median and ranges). With FiO2 = 0.5, PaO2 decreased 90% compared with baseline values and FAO2 decreased to 0.07 (0.06-0.07). No atelectasis was visible on computed tomography after either period, and we, therefore, conclude that the alveolar hypoxia was caused by the alveolar N2 accumulation/concentration and subsequently by the O2 depletion.

Moderate oxygen augments lipopolysaccharide-induced lung injury in mice

Despite the associated morbidity and mortality, underlying mechanisms leading to the development of acute lung injury (ALI) remain incompletely understood. Frequently, ALI develops in the hospital, coinciding with institution of various therapies, including the use of supplemental oxygen. Although pathological evidence of hyperoxia-induced ALI in humans has yet to be proven, animal studies involving high oxygen concentration reproducibly induce ALI. The potentially injurious role of lower and presumably safer oxygen concentrations has not been well characterized in any species. We hypothesized that in the setting of a preexisting insult to the lung, the addition of moderate-range oxygen can augment lung injury. Our model of low-dose intratracheal LPS (IT LPS) followed by 60% oxygen caused a significant increase in ALI compared with LPS or oxygen alone with increased alveolar neutrophils, histological injury, and epithelial barrier permeability. In the LPS plus oxygen group, regulatory T cell number was reduced, and macrophage activation markers were increased, compared with LPS alone. Antibody-mediated depletion of neutrophils significantly abrogated the observed lung injury for all measured factors. The enhanced presence of alveolar neutrophils in the setting of LPS and oxygen is due, at least in part, to elevated chemokine gradients signaling neutrophils to the alveolar space. We believe these results strongly support an effect of lower concentrations of oxygen to augment the severity of a mild preexisting lung injury and warrants further investigation in both animals and humans.

Protective role of Coenzyme Q10in two models of rat lung injury

Ischaemia-reperfusion injury is a life-threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q(10) (CoQ(10)) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q(10) pretreatment in a model of mild and severe lung injury. We evaluated the impact of CoQ(10) in a two-stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ(10) following oral therapy we administered high-dose oral CoQ(10) to rats (n = 6). In the second stage we evaluated the impact of CoQ(10) in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation. High-dose oral CoQ(10) for 7 days produced a 15-fold increase in plasma and a 3-fold increase in lung CoQ(10). In the normoxic lung, the injury-induced rise in peak airway pressure was reduced by CoQ(10) treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia-reperfusion injury, CoQ(10) did not reduce the injury-induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ(10) markedly reduced the increase in tumour necrosis factor-alpha in ischaemic compared with normoxic lung (P = 0.027). The effect of CoQ(10) pretreatment is insufficient to protect the lung against severe ischaemia-reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non-transplant surgery, CoQ(10) may have a protective role.

Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT=6 ml/kg and positive end-expiratory pressure (PEEP)=5 cmH(2)O for 1h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP=40 cmH(2)O), with interposed periods of PIP=10 cmH(2)O above a PEEP=15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury.

Exhaled Air Dispersion Distances During Noninvasive Ventilation via Different Respironics Face Masks

BackgroundAs part of our influenza pandemic preparedness, we studied the exhaled air dispersion distances and directions through two different face masks (Respironics; Murrysville, PA) attached to a human-patient simulator (HPS) during noninvasive positive-pressure ventilation (NPPV) in an isolation room with pressure of −5 Pa.MethodsThe HPS was positioned at 45° on the bed and programmed to mimic mild lung injury (oxygen consumption, 300 mL/min; lung compliance, 35 mL/cm H2O). Airflow was marked with intrapulmonary smoke for visualization. Inspiratory positive airway pressure (IPAP) started at 10 cm H2O and gradually increased to 18 cm H2O, whereas expiratory pressure was maintained at 4 cm H2O. A leakage jet plume was revealed by a laser light sheet, and images were captured by high definition video. Normalized exhaled air concentration in the plume was estimated from the light scattered by the smoke particles.FindingsAs IPAP increased from 10 to 18 cm H2O, the exhaled air of a low normalized concentration through the ComfortFull 2 mask (Respironics) increased from 0.65 to 0.85 m at a direction perpendicular to the head of the HPS along the median sagittal plane. When the IPAP of 10 cm H2O was applied via the Image 3 mask (Respironics) connected to the whisper swivel, the exhaled air dispersed to 0.95 m toward the end of the bed along the median sagittal plane, whereas higher IPAP resulted in wider spread of a higher concentration of smoke.ConclusionsSubstantial exposure to exhaled air occurs within a 1-m region, from patients receiving NPPV via the ComfortFull 2 mask and the Image 3 mask, with more diffuse leakage from the latter, especially at higher IPAP.

Dexmedetomidine–ketamine combination mitigates acute lung injury in haemorrhagic shock rats

Aim of the study Upregulation of pulmonary inflammatory molecules is crucial in mediating the development of acute lung injury induced by haemorrhagic shock. Dexmedetomidine and ketamine possess potent anti-inflammatory capacity. We sought to elucidate whether dexmedetomidine, ketamine, or dexmedetomidine–ketamine combination could mitigate acute lung injury in haemorrhagic shock rats. Methods Fifty adult male Sprague–Dawley rats were randomized to the sham-instrumented, haemorrhagic shock (HS), HS plus dexmedetomidine (HS-D), HS plus ketamine (HS-K), or HS plus dexmedetomidine–ketamine (HS-D + K) group ( n = 10 in each group). Haemorrhagic shock was induced by blood withdrawing and the mean blood pressure was maintained at 40–45 mmHg for 120 min. Resuscitation was then performed by infusion of shed blood/saline mixtures. After monitoring for another 8 h, rats were sacrificed. Results Histology findings and lung injury score analysis revealed moderate lung injury in rats of the HS, HS-D, and HS-K groups, whereas those of the HS-D + K group revealed mild lung injury. The effects of haemorrhagic shock on increasing cell number and protein concentration in bronchoalveolar lavage fluid as well as water content, leukocyte infiltration, and myeloperoxidase activity of lung tissues were significantly attenuated by dexmedetomidine–ketamine combination but not by dexmedetomidine or ketamine alone. Dexmedetomidine–ketamine combination, but not dexmedetomidine or ketamine alone, also significantly inhibited haemorrhagic shock-induced upregulation of pulmonary inflammatory molecules, including nitric oxide, prostaglandin E 2, chemokine (e.g., macrophage inflammatory protein-2), and cytokines [e.g., interleukin (IL)-1β, and IL-6]. Conclusions Dexmedetomidine–ketamine combination mitigates acute lung injury in haemorrhagic shock rats.

Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury

Prone position may delay the development of ventilator-induced lung injury (VILI), but the mechanisms require better elucidation. In experimental mild acute lung injury (ALI), arterial oxygen partial pressure (Pa O2), lung mechanics and histology, inflammatory markers [interleukin (IL)-6 and IL-1 beta], and type III procollagen (PCIII) mRNA expressions were analysed in supine and prone position. Wistar rats were randomly divided into two groups. In controls, saline was intraperitoneally injected while ALI was induced by paraquat. After 24-h, the animals were mechanically ventilated for 1-h in supine or prone positions. In ALI, prone position led to a better blood flow/tissue ratio both in ventral and dorsal regions and was associated with a more homogeneous distribution of alveolar aeration/tissue ratio reducing lung static elastance and viscoelastic pressure, and increasing end-expiratory lung volume and Pa O2. PCIII expression was higher in the ventral than dorsal region in supine position, with no regional changes in inflammatory markers. In conclusion, prone position may protect the lungs against VILI, thus reducing pulmonary stress and strain.

Exhaled Air and Aerosolized Droplet Dispersion During Application of a Jet Nebulizer

BackgroundAs part of our influenza pandemic preparedness, we studied the dispersion distances of exhaled air and aerosolized droplets during application of a jet nebulizer to a human patient simulator (HPS) programmed at normal lung condition and different severities of lung injury.MethodsThe experiments were conducted in a hospital isolation room with a pressure of − 5 Pa. Airflow was marked with intrapulmonary smoke. The jet nebulizer was driven by air at a constant flow rate of 6 L/min, with the mask reservoir filled with sterile water and attached to the HPS via a nebulizer mask. The exhaled leakage jet plume was revealed by a laser light sheet and images captured by high-definition video. Smoke concentration in the plume was estimated from the light scattered by smoke and droplet particles.FindingsThe maximum dispersion distance of smoke particles through the nebulizer side vent was 0.45 m lateral to the HPS at normal lung condition (oxygen consumption, 200 mL/min; lung compliance, 70 mL/cm H2O), but it increased to 0.54 m in mild lung injury (oxygen consumption, 300 mL/min; lung compliance, 35 mL/cm H2O), and beyond 0.8 m in severe lung injury (oxygen consumption, 500 mL/min; lung compliance, 10 mL/cm H2O). More extensive leakage through the side vents of the nebulizer mask was noted with more severe lung injury.InterpretationHealth-care workers should take extra protective precaution within at least 0.8 m from patients with febrile respiratory illness of unknown etiology receiving treatment via a jet nebulizer even in an isolation room with negative pressure.

Epithelial Cell Apoptosis Causes Acute Lung Injury Masquerading as Emphysema

Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal microcystin (MC) to induce apoptosis, intratracheal porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups were further analyzed by air-saline quasistatic measurements, surfactant staining, and surfactant functional studies. Mice treated with MC showed evidence of reversible airspace enlargement. In contrast, PPE-treated mice showed irreversible airspace enlargement. The airspace enlargement in MC-treated mice was associated with an increase in elastic recoil due to an increase in alveolar surface tension. PPE-treated mice showed a loss of lung elastic recoil and normal alveolar surface tension, a pattern more consistent with human emphysema. Airspace enlargement that occurs with the MC model of pulmonary epithelial cell apoptosis displays physiology distinct from human emphysema. Reversibility, restrictive physiology due to changes in surface tension, and alveolar enlargement associated with heterogeneous alveolar collapse are most consistent with a mild acute lung injury. Inflation near total lung capacity gives the appearance of enlarged alveoli as neighboring collapsed alveoli exert tethering forces.

Hemodynamic effects of PEEP in a porcine model of HCl‐induced mild acute lung injury

Positive end-expiratory pressure (PEEP) and sustained inspiratory insufflations (SI) during acute lung injury (ALI) are suggested to improve oxygenation and respiratory mechanics. We aimed to investigate the hemodynamic effects of PEEP with and without alveolar recruiting maneuver in a mild ALI model induced by inhalation of hydrochloric acid. Thirty-two pigs were randomly allocated into four groups (Control-PEEP, Control-SI, ALI-PEEP and ALI-SI). ALI was induced by intratracheal instillation of hydrochloric acid. PEEP values were progressively increased and decreased from 5, 10, 15 and 20 cmH2O in all groups. Three SIs maneuvers of 30 cmH2O for 20 s were applied to the assignable groups between each PEEP level. Transesophageal echocardiography (TEE), global hemodynamics, oxygenation indexes and gastric tonometry were measured 5 min after the maneuvers had been concluded and at each established value of PEEP (5, 10, 15 and 20 cmH2O). The cardiac index, ejection fraction and end-diastolic volume of right ventricle were significantly (P < 0.001) decreased with PEEP in both Control and ALI groups. Left ventricle echocardiography showed a significant decrease in end-diastolic volume at 20 cmH2O of PEEP (P < 0.001). SIs did not exert any significant hemodynamic effects either early (after 5 min) or late (after 3 h). In a mild ALI model induced by inhalation of hydrochloric acid, significant hemodynamic impairment characterized by cardiac function deterioration occurred during PEEP increment, but SI, probably due to low applied values (30 cmH2O), did not exert further negative hemodynamic effects. PEEP should be used cautiously in ALI caused by acid gastric content inhalation.

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

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. Prospective, randomized, controlled experimental study. University research laboratory. One hundred twenty-eight BALB/c mice (20-25 g). 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). 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. 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.