A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury

BackgroundBiologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller) was compared to control mode ventilation with and without a recruitment manoeuvre – 40 cm H₂O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model.MethodsWe compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (F_IO₂ = 0.3; PEEP 5 cm H₂O) in control mode until PaO₂ decreased to 60 mm Hg with oleic acid infusion (PaO₂/F_IO₂ <200 mm Hg). Additional PEEP to 10 cm H₂O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury.ResultsPaO₂ and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry.ConclusionsIn this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.     

Effect of recombinant SP-C surfactant in a porcine lavage model of acute lung injury.

Synthetic surfactants allow examination of the effects of specific components of natural surfactant. To determine whether surfactant containing apoprotein C, dipalmitoyl-phosphatidylcholine, phosphatidylglycerol, and palmitic acid restores gas-exchanging function in acute lung injury (ALI), we administered such surfactant (in doses of 50 or 100 mg/kg and in volumes from 1 to 6 ml/kg) or phospholipid (PL) alone, by intratracheal instillation, to pigs with ALI induced by massive saline lavage. Animals ventilated with 100% O(2) and receiving 1, 2, 4, or 6 ml/kg of 50 mg/kg recombinant surfactant apoprotein C (rSP-C) surfactant or 2 ml/kg of 50 mg/kg PL (control) had mean arterial PO(2) values, 4 h after treatment, of 230, 332, 130, 142, or 86 Torr, respectively. Animals receiving 1, 2, or 4 ml/kg of 100 mg/kg rSP-C surfactant or 2 ml/kg of 100 mg/kg PL (control) had mean arterial PO(2) values of 197, 214, 148, or 88 Torr, respectively. Surfactant PL distribution was homogeneous. Hyaline membrane formation was reduced in treated animals. Thus, in this model of ALI, rSP-C with PL has the capacity to improve gas exchange and possibly modify lung injury.     

Sustained inflation and incremental mean airway pressure trial during conventional and high-frequency oscillatory ventilation in a large porcine model of acute respiratory distress syndrome

Background

To compare the effect of a sustained inflation followed by an incremental mean airway pressure trial during conventional and high-frequency oscillatory ventilation on oxygenation and hemodynamics in a large porcine model of early acute respiratory distress syndrome.

Methods

Severe lung injury (Ali) was induced in 18 healthy pigs (55.3 ± 3.9 kg, mean ± SD) by repeated saline lung lavage until PaO₂ decreased to less than 60 mmHg. After a stabilisation period of 60 minutes, the animals were randomly assigned to two groups: Group 1 (Pressure controlled ventilation; PCV): FIO₂ = 1.0, PEEP = 5 cmH₂O, V_T = 6 ml/kg, respiratory rate = 30/min, I:E = 1:1; group 2 (High-frequency oscillatory ventilation; HFOV): FIO₂ = 1.0, Bias flow = 30 l/min, Amplitude = 60 cmH₂O, Frequency = 6 Hz, I:E = 1:1. A sustained inflation (SI; 50 cmH₂O for 60s) followed by an incremental mean airway pressure (mPaw) trial (steps of 3 cmH₂O every 15 minutes) were performed in both groups until PaO₂ no longer increased. This was regarded as full lung inflation. The mPaw was decreased by 3 cmH₂O and the animals reached the end of the study protocol. Gas exchange and hemodynamic data were collected at each step.

Results

The SI led to a significant improvement of the PaO₂/FiO₂-Index (HFOV: 200 ± 100 vs. PCV: 58 ± 15 and T_Ali: 57 ± 12; p < 0.001) and PaCO₂-reduction (HFOV: 42 ± 5 vs. PCV: 62 ± 13 and T_Ali: 55 ± 9; p < 0.001) during HFOV compared to lung injury and PCV. Augmentation of mPaw improved gas exchange and pulmonary shunt fraction in both groups, but at a significant lower mPaw in the HFOV treated animals. Cardiac output was continuously deteriorating during the recruitment manoeuvre in both study groups (HFOV: T_Ali: 6.1 ± 1 vs. T₇₅: 3.4 ± 0.4; PCV: T_Ali: 6.7 ± 2.4 vs. T₇₅: 4 ± 0.5; p < 0.001).

Conclusion

A sustained inflation followed by an incremental mean airway pressure trial in HFOV improved oxygenation at a lower mPaw than during conventional lung protective ventilation. HFOV but not PCV resulted in normocapnia, suggesting that during HFOV there are alternatives to tidal ventilation to achieve CO₂-elimination in an "open lung" approach.     

Effect of position, nitric oxide, and almitrine on lung perfusion in a porcine model of acute lung injury.

In a porcine model of oleic acid-induced lung injury, the effects of inhaled nitric oxide (iNO) and intravenous almitrine bismesylate (ivALM), which enhances the hypoxic pulmonary vasoconstriction on the distribution of regional pulmonary blood flow (PBF), were assessed. After injection of 0.12 ml/kg oleic acid, 20 anesthetized and mechanically ventilated piglets [weight of 25 +/- 2.6 (SD) kg] were randomly divided into four groups: supine position, prone position, and 10 ppm iNO for 40 min followed by 4 microg x kg(-1) x min(-1) ivALM for 40 min in supine position and in prone position. PBF was measured with positron emission tomography and H(2)15O. The redistribution of PBF was studied on a pixel-by-pixel basis. Positron emission tomography scans were performed before and then 120, 160, and 200 min after injury. With prone position alone, although PBF remained prevalent in the dorsal regions it was significantly redistributed toward the ventral regions (P < 0.001). A ventral redistribution of PBF was also obtained with iNO regardless of the position (P = 0.043). Adjunction of ivALM had no further effect on PBF redistribution. PP and iNO have an additive effect on ventral redistribution of PBF.     

Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

Background

Proline-rich tyrosine kinase 2 (Pyk2) is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI) remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo.

Methods

C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically.

Results

Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1) myeloperoxidase content in lung tissues, 2) vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3) the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment.

Conclusions

These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and that pharmacological inhibition of Pyk2 might provide a potential therapeutic strategy in the pretreatment for patients at imminent risk of developing acute lung injury.     

Very low tidal volume ventilation with associated hypercapnia--effects on lung injury in a model for acute respiratory distress syndrome

Background

Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome.

Methodology/Principal Findings

In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8–10 ml/kg/PaCO₂ = 40 mm Hg; Group 2: tidal volume = 4–5 ml/kg/PaCO₂ = 80 mm Hg; Group 3: tidal volume = 3–4 ml/kg/PaCO₂ = 120 mm Hg; Group 4: tidal volume = 2–3 ml/kg/PaCO₂ = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO₂ were found in all low tidal volume/hypercapnia groups (group 2, 3, 4) as compared to the group with conventional tidal volume/normocapnia (group 1). The reduction of the tidal volume below 4–5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy.

Conclusion

Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4–5 ml/kg/PaCO₂ 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained.     

High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion

Ischemia-reperfusion not only damages the affected organ but also leads to remote organ injuries. Hepatic inflow interruption usually occurs during hepatic surgery. To investigate the influence of liver ischemia-reperfusion on lung injury and to determine the contribution of tidal volume settings on liver ischemia-reperfusion-induced lung injury, we studied anesthetized and mechanically ventilated rats in which the hepatic inflow was transiently interrupted twice for 15 min. Two tidal volumes, 6 ml/kg as a low tidal volume (IR-LT) and 24 ml/kg as a high tidal volume (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation, 6 ml/kg (NC-LT) and 24 ml/kg (NC-HT). Both the IR-HT and IR-LT groups had a gradual decline in the systemic blood pressure and a significant increase in plasma TNF-alpha concentrations. Of the four groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet-to-dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the bronchoalveolar lavage fluid TNF-alpha concentration. Furthermore, only in the IR-HT group was airway pressure increased significantly during the 6-h reperfusion period. These findings suggest that liver ischemia-reperfusion caused systemic inflammation and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.     

A new porcine model of reperfusion injury after lung transplantation

Rodent models have been described to investigate lung preservation and reperfusion injury but have significant disadvantages. In large animals single lung transplant studies are probably optimal but problems remain over the ability to rigorously separate the lungs for assessment while promoting medium to long-term animal survival for meaningful investigation. Our aim was to develop a novel and refined large animal model to assess reperfusion injury in the transplanted lung, overcoming the difficulties associated with existing models. Specifically, small animal models of lung transplantation usually have short perfusion times (often one hour) and include extracorporeal circuits while larger animal models often require the contralateral lung to be excluded after transplantation-an unphysiological situation under which to evaluate the graft. A porcine model of left lung allotransplantation was developed in which native and donor lungs are individually ventilated. Sampling catheters placed within the graft lung allowed specimen withdrawal without mixing of blood from the contralateral lung after reimplantation. The model permits a variety of clinical scenarios to be simulated with the native lung supporting the animal irrespective of function in the graft. This model has been used in over 60 transplant procedures with a postoperative survival time of 12 h being readily achieved. The mean operating time was 2.6 h. The mortality rate is 4% in our series. We have found the model to be reliable, reproducible and flexible. We propose this model as an adaptable investigation for evaluating lung reperfusion injury and preservation.     

Partial liquid ventilation improves gas exchange and increases EELV in acute lung injury

Gas exchange is improved during partial liquidventilation with perfluorocarbon in animal models of acute lung injury.The specific mechanisms are unproved. We measured end-expiratory lung volume (EELV) by null-point body plethysmography in anesthetized sheep.Measurements of gas exchange and EELV were made before and after acutelung injury was induced with intravenous oleic acid to decrease EELVand worsen gas exchange. Measurements of gas exchange and EELV wereagain performed after partial liquid ventilation with 30 ml/kg ofperfluorocarbon and compared with gas-ventilated controls. Oxygenationwas significantly improved during partial liquid ventilation, and EELV(composite of gas and liquid) was significantly increased, comparedwith preliquid ventilation values and gas-ventilated controls. Weconclude that partial liquid ventilation may directly recruitconsolidated alveoli in the lung-injured sheep and that this may be onemechanism whereby gas exchange is improved.

     

Inhibition of glycolysis alleviates lipopolysaccharide-induced acute lung injury in a mouse model

Gluconic metabolic reprogramming, immune response, and inflammation are intimately linked. Glycolysis involves in the pathologic progress in acute and chronic inflammatory diseases. However, the involvement of glycolysis in the acute lung injury (ALI) is still unclear. This study investigated the role of glycolysis in an animal model of ALI. First, we found that lactate content in serum was remarkably increased in ALI patients and a murine model induced by intratracheal administration of lipopolysaccharide (LPS). The key proteins involving in glycolysis were robustly elevated, including HK2, PKM2, and HIF-1α. Intriguingly, inhibition of glycolysis by 2-deoxyglucose (2-DG) pronouncedly attenuated the lung tissue pathological injury, accumulation of neutrophil, oxidative stress, expression of proinflammatory factors in the lung of ALI mice induced by LPS. The 2-DG treatment also strongly suppressed the activation of the NOD-like receptor (NLR) family and pyrin domain-containing protein 3 (NLRP3) inflammasome. Furthermore, we investigated the role of glycolysis in the inflammatory response of primary murine macrophages activated by LPS in vitro. We found that the 2-DG treatment remarkably reduced the expression of proinflammatory factors induced by LPS, including tumor necrosis factor-α messenger RNA (mRNA), pro-interleukin (IL)-1β mRNA, pro-IL-18 mRNA, NLRP3 mRNA, caspase-1 mRNA, and IL-1β protein. Altogether, these data provide a novel link between gluconic metabolism reprogramming and uncontrolled inflammatory response in ALI. This study suggests glycolytic inhibition as an effective anti-inflammatory strategy in treating ALI.     

Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury

Background

New animal models of chronic pulmonary hypertension in mice are needed. The injection of monocrotaline is an established model of pulmonary hypertension in rats. The aim of this study was to establish a murine model of pulmonary hypertension by injection of the active metabolite, monocrotaline pyrrole.

Methods

Survival studies, computed tomographic scanning, histology, bronchoalveolar lavage were performed, and arterial blood gases and hemodynamics were measured in animals which received an intravenous injection of different doses of monocrotaline pyrrole.

Results

Monocrotaline pyrrole induced pulmonary hypertension in Sprague Dawley rats. When injected into mice, monocrotaline pyrrole induced dose-dependant mortality in C57Bl6/N and BALB/c mice (dose range 6–15 mg/kg bodyweight). At a dose of 10 mg/kg bodyweight, mice developed a typical early-phase acute lung injury, characterized by lung edema, neutrophil influx, hypoxemia and reduced lung compliance. In the late phase, monocrotaline pyrrole injection resulted in limited lung fibrosis and no obvious pulmonary hypertension.

Conclusion

Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.     

Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious,ventilator-induced lung injury model

Background

Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury.

Methods

Prospective, randomized, controlled animal study using male, healthy adults Sprague-Dawley rats weighing 300-350 g. Animals were anesthetized and randomized to spontaneous breathing and to two different mechanical ventilation strategies for 4 hours: high tidal volume (V_T) (20 ml/kg) and low V_T (6 ml/kg). Histological evaluation, TLR2, TLR4, IRAK3 gene expression, IRAK-3 protein levels, inhibitory kappa B alpha (IκBα), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL6) gene expression in the lungs and TNF-α and IL-6 protein serum concentrations were analyzed.

Results

High V_T mechanical ventilation for 4 hours was associated with a significant increase of TLR4 but not TLR2, a significant decrease of IRAK3 lung gene expression and protein levels, a significant decrease of IκBα, and a higher lung expression and serum concentrations of pro-inflammatory cytokines.

Conclusions

The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar to that observed during infections.     

Detection of porcine oleic acid-induced acute lung injury using pulmonary acoustics.

To evaluate the utility of monitoring the sound-filtering characteristics of the respiratory system in the assessment of acute lung injury (ALI), we injected a multifrequency broadband sound signal into the airway of five anesthetized, intubated pigs, while recording transmitted sound over the trachea and on the chest wall. Oleic acid injections effected a severe lung injury predominantly in the dependent lung regions, increasing venous admixture from 6 +/- 1 to 54 +/- 8% (P < 0.05) and reducing dynamic respiratory system compliance from 19 +/- 0 to 12 +/- 2 ml/cmH(2)O (P < 0.05). A two- to fivefold increase in sound transfer function amplitude was seen in the dependent (P < 0.05) and lateral (P < 0.05) lung regions; no change occurred in the nondependent areas. High within-subject correlations were found between the changes in dependent lung sound transmission and venous admixture (r = 0.82 +/- 0.07; range 0.74-0.90) and dynamic compliance (r = -0.87 +/- 0.05; -0.80 to -0.93). Our results indicate that the acoustic changes associated with oleic acid-induced lung injury allow monitoring of its severity and distribution.     

Macrophages mediate lung inflammation in a mouse model of ischemic acute kidney injury

Serum IL-6 is increased in acute kidney injury (AKI) and inhibition of IL-6 reduces AKI-mediated lung inflammation. We hypothesized that circulating monocytes produce IL-6 and that alveolar macrophages mediate lung inflammation after AKI via chemokine (CXCL1) production. To investigate systemic and alveolar macrophages in lung injury after AKI, sham operation or 22 min of renal pedicle clamping (AKI) was performed in three experimental settings: 1) systemic macrophage depletion via diphtheria toxin (DT) injection to CD11b-DTR transgenic mice, 2) DT injection to wild-type mice, and 3) alveolar macrophage depletion via intratracheal (IT) liposome-encapsulated clodronate (LEC) administration to wild-type mice. In mice with AKI and systemic macrophage depletion (CD11b-DTR transgenic administered DT) vs. vehicle-treated AKI, blood monocytes and lung interstitial macrophages were reduced, renal function was similar, serum IL-6 was increased, lung inflammation was improved, lung CXCL1 was reduced, and lung capillary leak was increased. In wild-type mice with AKI administered DT vs. vehicle, serum IL-6 was increased. In mice with AKI and alveolar macrophage depletion (IT-LEC) vs. AKI with normal alveolar macrophage content, blood monocytes and lung interstitial macrophages were similar, alveolar macrophages were reduced, renal function was similar, lung inflammation was improved, lung CXCL1 was reduced, and lung capillary leak was increased. In conclusion, administration of DT in AKI is proinflammatory, limiting the use of the DTR-transgenic model to study systemic effects of AKI. Mice with AKI and either systemic mononuclear phagocyte depletion or alveolar macrophage depletion had reduced lung inflammation and lung CXCL1, but increased lung capillary leak; thus, mononuclear phagocytes mediate lung inflammation, but they protect against lung capillary leak after ischemic AKI. Since macrophage activation and chemokine production are key events in the development of acute lung injury (ALI), these data provide further evidence that AKI may cause ALI.     

Detecting lung overdistention in newborns treated with high-frequency oscillatory ventilation.

Positive airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV) increases lung volume and can lead to lung overdistention with potentially serious adverse effects. To date, no method is available to monitor changes in lung volume (DeltaVL) in HFOV-treated infants to avoid overdistention. In five newborn piglets (6-15 days old, 2.2-4.2 kg), we investigated the use of direct current-coupled respiratory inductive plethysmography (RIP) for this purpose by evaluating it against whole body plethysmography. Animals were instrumented, fitted with RIP bands, paralyzed, sedated, and placed in the plethysmograph. RIP and plethysmography were simultaneously calibrated, and HFOV was instituted at varying Paw settings before (6-14 cmH(2)O) and after (10-24 cmH(2)O) repeated warm saline lung lavage to induce experimental surfactant deficiency. Estimates of Delta VL from both methods were in good agreement, both transiently and in the steady state. Maximal changes in lung volume (Delta VL(max)) from all piglets were highly correlated with Delta VL measured by RIP (in ml) = 1.01 x changes measured by whole body plethysmography - 0.35; r(2) = 0.95. Accuracy of RIP was unchanged after lavage. Effective respiratory system compliance (Ceff) decreased after lavage, yet it exhibited similar sigmoidal dependence on Delta VL(max) pre- and postlavage. A decrease in Ceff (relative to the previous Paw setting) as Delta VL(max) was methodically increased from low to high Paw provided a quantitative method for detecting lung overdistention. We conclude that RIP offers a noninvasive and clinically applicable method for accurately estimating lung recruitment during HFOV. Consequently, RIP allows the detection of lung overdistention and selection of optimal HFOV from derived Ceff data.     

High in comparison with low tidal volume ventilation aggravates oxidative stress-induced lung injury

Ventilator settings influence the development and outcome of acute lung injury. This study investigates the influence of low versus high tidal volume (V(t)) on oxidative stress-induced lung injury.Isolated rabbit lungs were subjected to one of three ventilation patterns (V(t)-positive end-expiratory pressure, PEEP): LVZP (6 ml/kg-0 cm H(2)O), HVZP (12 ml/kg-0 cm H(2)O), LV5P (6 ml/kg-5 cm H(2)O). These ventilation patterns allowed a comparison between low and high V(t) without dependence on peak inspiratory pressure (PIP). Infusion of hypochlorite (1000 nmol/min) or buffer (control) was started at t=0 min. Pulmonary artery pressure (PAP), PIP and weight were continuously recorded. Capillary filtration coefficient [K(f,c) (10(-4) ml s(-1) cm H(2)O(-1) g(-1))] was gravimetrically determined (-15/30/60/90/120 min).PIP averaged 5.8+/-0.6/13.9+/-0.6/13.9+/-0.4 cm H(2)O in the LVZP, HVZP and LV5P groups. PIP, K(f,c) or PAP did not change in control groups, indicating that none of the ventilation patterns caused lung injury by themselves. Hypochlorite-induced increase in K(f,c) but not hypochlorite-induced increase in PAP, was significantly attenuated in the LVZP-/LV5P- versus the HVZP-group (K(f,c,max.) 1.0+/-0.23/1.4+/-0.40 versus 3.2+/-1.0*). Experiments with hypochlorite were terminated due to excessive edema (>50 g) at 97+/-2.2/94.5+/-4.5 min in the LVZP-/LV5P-group versus 82+/-3.8* min in the HVZP-group (*: P<0.05).Low V(t) attenuated oxidative stress-induced increase in vascular permeability independently from PIP and PEEP.     

A model of constant-flow ventilation in a dog lung

A semiempirical model of constant-flow ventilation (CFV) is developed to test the hypothesis that a three-zone serial model with the following characteristics can explain the adequate CO2 transport observed during CFV: 1) a zone of jet recirculation immediately downstream of the catheter in which convection dominates; 2) a zone influenced by turbulence but with little or no bulk flow; and 3) a peripheral zone, free of turbulence, in which transport is governed by molecular and augmented diffusion. Interactions between turbulent eddies and cardiogenic oscillations are included using a modification of Taylor dispersion theory according to the formulation of Kamm et al. Predicted values for arterial PCO2 are reasonably similar to experimental results for He-O2, air, and SF6-O2 mixtures for catheter flow rates from 0.2 to 1.6 l/s. Specific impedance to gas exchange was found to be largest immediately proximal to the end of turbulent mixing zone, where transport is governed by low-level eddy mixing and molecular diffusion. Simulations suggest that, during CFV, cardiogenic oscillations augment gas exchange primarily by promoting turbulent eddy dispersion in the distal airways and by extending the length of the turbulent mixing zone. Even small displacements of the catheter are shown to have a dramatic effect on gas exchange.     

High-volume ventilation induces pentraxin 3 expression in multiple acute lung injury models in rats

Pentraxin 3 (PTX3) is an acute-phase protein, which can be produced by a variety of tissue cells at the site of infection or inflammation. It plays an important role in innate immunity in the lung and in mediating acute lung injury. The aim of this study was to determine the effect of mechanical ventilation on PTX3 expression in multiple lung injury models. Male Sprague-Dawley rats were challenged with intravenous injection of lipopolysaccharide (LPS) or hemorrhage followed by resuscitation (HS). The animals were then subjected to either relatively higher (12 ml/kg) or lower (6 ml/kg, positive end-expiratory pressure of 5 cmH(2)O) volume ventilation for 4 h. High-volume ventilation significantly enhanced PTX3 expression in the lung, either alone or in combination with LPS or hemorrhage. A significant increase of PTX3 immunohistochemistry staining in the lung was seen in all injury groups. The PTX3 expression was highly correlated with the severity of lung injury determined by blood gas, lung elastance, and wet-to-dry ratio. To determine the effects of HS, LPS, or injurious ventilation (25 ml/kg) alone on PTX3 expression, another group of rats was studied. Injurious ventilation significantly damaged the lung and increased PTX3 expression. A local expression of PTX3 induced by high-volume ventilation, either alone or in combination with other pathological conditions, suggests that it may be an important mediator in ventilator-induced lung injury.