Protective effects of oxidized phospholipids on ventilator-induced lung injury

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Track 13. Respiratory Mechanics 5356 We-Th, no. 37 (P64) Biomechanics of self-excited oscillation induced by flow-structure interaction in airway constriction S. Deguchi, '~ Miyake, A. Shiota, '~ Tamura, S. Washio. Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan Self-excited oscillation of airway constrictions such as glottis (i.e., the sound source of voice or snoring) is induced by interaction between respiratory flow and tissue structure. The biomechanics involved in the airway constriction oscillation is crucial for considering better treatments for phonation/snoring disorders as well as designs for artificial vocal fold apparatus. Its generation mechanism, however, remains elusive since no experimental description of the relation between airflow pressure and structure deformation at high fun- damental frequencies of >100Hz (i.e., the order of magnitude of the voice pitch) has ever appeared. Here, the pressure-deformation relation was studied with experimental and analytical approaches. In the first part of the present study, we built a new experimental setup mimicking the human airway including a vocal fold model, which enables simultaneous measurement of airflow pressure and structure deformation at arbitrary points along a self-sustained oscillating constriction. The pressures were measured by semiconductor pres- sure transducers, the measurement positions of which can be regulated by a sliding stage. Meanwhile, the constriction deformations were detected by analyzing ultra-high speed camera images synchronized with the pressure measurements. The pressure-deformation waveforms were obtained at various magnitudes of adjustable parameters, e.g., tension in a rubber sheet that models one pair of the vocal folds. The results revealed a process in which the constriction oscillation is gradually being self-excited and finally sustained, demonstrating critical biomechanical events in phonation and snoring. The second part of this study dealt with a theory of the mechanism by which the vocal folds are self-excited by respiratory airflow stimuli, leading onset of the oscillation. Governing equations for the airway constriction mechanics were analytically derived. A perturbation analysis was applied to the analytical model, yielding a threshold mechanical condition where the oscillation will initiate. These experimental and analytical findings will contribute to better understanding of the phonation/snoring mechanism in respiratory mechanics. 4296 We-Th, no. 38 (P64) Protective effects of oxidized phospholipids on ventilator-induced lung injury A.A. Birukova 1, S.A. Nonas 2, I. Miller2, S. Chatchavalvanich 1, J.G.N. Garcia 1, K.G. Birukov 1. 1Department of Medicine, University of Chicago, Chicago, Illinois, USA, 2Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Acute lung injury (ALl) is a devastating syndrome characterized by pul- monary inflammation and vascular barrier dysfunction with protein rich edema. Mechanical ventilation at high tidal volumes can worsen existing ALl and even cause ventilator-induced lung injury (VILI) de novo. Previous stud- ies have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero- 3-phosphorylcholine (OxPAPC) enhances basal endothelial cell (EC) barrier properties and prevents acute lung inflammation and EC dysfunction in re- sponse to bacterial lipopolysaccharide (LPS) via direct Rac-Cdc42-mediated effects on EC cytoskeleton and via competitive inhibition of LPS binding to toll-like receptor 4 (TLR4). Adult male Brown Norway rats (250-350g) were ventilated at low tidal volume (LTV, 7 ml/kg) or high tidal volume (HTV, 20 ml/kg) for 2 hrs, 85 breaths/min. A subset of animals received intravenous OxPAPC (l.5mg/kg) at the start of mechanical ventilation. Bronchoalveolar lavage (BAL) cell count and protein concentration were measured as markers of inflammation and vascular permeability. EC monolayer barrier function in vitro was assessed by morphological analysis of agonist-induced gap formation. HTV caused a 70% increase in BAL total cell count (p <0.05) and a 169% in- crease in BAL protein (p < 0.01) compared with LTV controls. OxPAPC reduced HTV-induced elevations in total cell count (41% decrease vs. HTV alone) and protein (42% decrease vs. HTV alone). In vitro, high magnitude cyclic stretch (18% elongation) applied to lung EC increased thrombin-induced bar- rier dysfunction, whereas OxPAPC dramatically attenuated thrombin-induced EC disruption and enhanced EC recovery phase. These studies demonstrate for the first time the protective effect of oxidized phospholipids on ventilator induced lung inflammation and barrier dysfunction independent on TLR4- mediated inflammatory cascade. Supported by NIH grants HL75349, HL76259, HL58064 4868 We-Th, no. 39 (P64) Modeling pulmonary transport of liquid plugs in microfluidic channels C. Ody, E. de Langre, C.N. Baroud. Laberateire d'Hydredynamique (LadHyX), Ecole Polytechnique, Palaiseau, France Liquid plugs may be present in the lung either pathologically or for medication delivery. The transport of these plugs is complicated by the complex pattern of $601 bifurcations in the pulmonary tree; for this reason, understanding the behavior of a plug at a bifurcation constitutes an important milestone in the modeling of lung airway re-opening. Modern microfluidic fabrication techniques allow us to make model systems consisting either of one bifurcation or a network of successive branchings. The typical length scales of the microfluidic channels also allow us to work in the range where capillary forces are dominant, thus modeling the small scales in the lung. We inject plugs of liquid of controlled length (L) into the microfluidic channel and observe the behavior as the plug reaches a bifurcation, driven by a constant pressure (P). The parameter space L-P may therefore be mapped experimentally. In a T-shaped bifurcation, we observe three main regimes with (a) the plug remaining trapped at the entrance of the bifurcation, (b) dividing into two daughter plugs in the daughter channels, or (c) popping and opening the channel to air flow. A physical model is developed to understand the three behavior regimes, based on a balance of capillary pressure-jumps and the driving pressure. The transition between regimes (b) and (c) is then explained by geometric arguments. For a Y-shaped bifurcation, the behavior also depends on the angle made by the daughter branches. For a sufficiently large angle, we recover the behavior found for the T junction, with a small correction due to the geometry. For small branching angles, we find that no threshold pressure exists. These studies are then applied to the study of a more complex network of successive bifurcations where the interest is geared towards the behavior of the complete network rather than of a single liquid plug. 5401 We-Th, no. 40 (P64) Three-component gas velocity mapping by magnetic resonance imaging E. Durand 1, L. de Rochefort 1, X. Maltre 1, R. Fodil 2, B. Louis 2, L. Vial 3, L. Darrasse 1, G. Caillibotte 3, G. Sbirlea-Apiou 3, J. Bittoun 1, D. Isabey 2. 1CNRS/Universit6 Paris-Sud (U2R2M-UMR8081), Bic~tre, France, 21NSERM, UMR 651; Universit~ Paris XIL Cr~teil, France, 3Air Liquide, Groupe Gaz M~dicaux, Les Loges en Josas, France. In 1982, magnetic resonance imaging (MRI) was proposed to acquire velocity maps, by phase-encoding the signal emitted by hydrogen nuclei [1]. This "phase-contrast MRr' technique has been applied in liquids, mostly for blood flow acquisitions in vive [2]. MRI is neither limited to liquid state norto hydrogen. However, gas MRI was hindered by an inherent low nucleus density. In 1994, this limitation was overcome with hyperpolarised xenon and images on gas were acquired in mouse [3]. Since then, many studies have been reported with hyperpolarised gas imaging. Here, we report the combination of phase-contrast technique and hyperpo- larised helium-3 to acquire velocity maps of gas in a 1.5 T MRI device. Helium-3 (stable isotope) was hyperpolarised on-site by metastability-exchange optical pumping. It was then mixed with nitrogen and injected into various geometries promoting 3D-airway-like flows (straight, U-shaped, and bifurcation pipes). MRI velocity maps were acquired in a 1 cm thick slice and a field-of-view of 10 cm. In-plane pixel size was 1.6 mm. The three velocity components were acquired in about 1 s. Flows computed from integration of the measured velocities matched within 5% the input flows given by a mass flowmeter. Velocity maps also were found in good agreement for both the through-plane component and the secondary mo- tion with predicted velocities: either Poiseuille flow (straight pipe) or simulated 3D-flows (other). Finally, the feasibility in-vive was demonstrated in the trachea of a human volunteer. This technique proves reliable to map the three components of gas velocity, even through opaque walls and with no need for an external probe. Then, it can be used for experimental validation of numerical models in 3D-reconstructed geometries. It also opens an original way for airflow measurements in vive. Acknowledgements: Laboratoire Kastler Brossel (ENS) - Minist~re de la Recherche (RNTS01B0338) References [1] Moran.Magn. Reson. Imag. 1982; 1: 197-203. [2] Dumoulin. Acta Radiol. Supp. 1986; 369: 17-20. [3] Albert. Nature 1994; 370: 199-201. 5549 We-Th, no. 41 (P64) Oscillatory flow in image-based bronchial airway model G. Tanaka 1, G. Inagaki 1, M. Hishida 1, H. Haneishi 2, X. Hu 3. 1Department of Electronics and Mechanical Engineering, Chiba University, Chiba, Japan, 2Research Center for Frontier Medical Engineering, Chiba University, Chiba, Japan, 3Fluent Asia Pacific Co. Ltd., Tokyo, Japan Computational fluid dynamics (CFD) simulation was carried out for an oscil- latory flow in a 3-D realistic model of the human central airways, and the effect of airway geometry on the oscillatory flow stricture was revealed. The computational model of multi-branching airways was prepared from X-ray CT

Transcript of Protective effects of oxidized phospholipids on ventilator-induced lung injury

Page 1: Protective effects of oxidized phospholipids on ventilator-induced lung injury

Track 13. Respiratory Mechanics

5356 We-Th, no. 37 (P64) Biomechanics of self-excited oscillation induced by flow-structure interaction in airway constriction S. Deguchi, '~ Miyake, A. Shiota, '~ Tamura, S. Washio. Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan

Self-excited oscillation of airway constrictions such as glottis (i.e., the sound source of voice or snoring) is induced by interaction between respiratory flow and tissue structure. The biomechanics involved in the airway constriction oscillation is crucial for considering better treatments for phonation/snoring disorders as well as designs for artificial vocal fold apparatus. Its generation mechanism, however, remains elusive since no experimental description of the relation between airflow pressure and structure deformation at high fun- damental frequencies of >100Hz (i.e., the order of magnitude of the voice pitch) has ever appeared. Here, the pressure-deformation relation was studied with experimental and analytical approaches. In the first part of the present study, we built a new experimental setup mimicking the human airway including a vocal fold model, which enables simultaneous measurement of airflow pressure and structure deformation at arbitrary points along a self-sustained oscillating constriction. The pressures were measured by semiconductor pres- sure transducers, the measurement positions of which can be regulated by a sliding stage. Meanwhile, the constriction deformations were detected by analyzing ultra-high speed camera images synchronized with the pressure measurements. The pressure-deformation waveforms were obtained at various magnitudes of adjustable parameters, e.g., tension in a rubber sheet that models one pair of the vocal folds. The results revealed a process in which the constriction oscillation is gradually being self-excited and finally sustained, demonstrating critical biomechanical events in phonation and snoring. The second part of this study dealt with a theory of the mechanism by which the vocal folds are self-excited by respiratory airflow stimuli, leading onset of the oscillation. Governing equations for the airway constriction mechanics were analytically derived. A perturbation analysis was applied to the analytical model, yielding a threshold mechanical condition where the oscillation will initiate. These experimental and analytical findings will contribute to better understanding of the phonation/snoring mechanism in respiratory mechanics.

4296 We-Th, no. 38 (P64) Protective effects of oxidized phospholipids on ventilator-induced lung in jury

A.A. Birukova 1 , S.A. Nonas 2, I. Miller 2, S. Chatchavalvanich 1 , J.G.N. Garcia 1 , K.G. Birukov 1 . 1Department of Medicine, University of Chicago, Chicago, Illinois, USA, 2Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA

Acute lung injury (ALl) is a devastating syndrome characterized by pul- monary inflammation and vascular barrier dysfunction with protein rich edema. Mechanical ventilation at high tidal volumes can worsen existing ALl and even cause ventilator-induced lung injury (VILI) de novo. Previous stud- ies have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero- 3-phosphorylcholine (OxPAPC) enhances basal endothelial cell (EC) barrier properties and prevents acute lung inflammation and EC dysfunction in re- sponse to bacterial lipopolysaccharide (LPS) via direct Rac-Cdc42-mediated effects on EC cytoskeleton and via competitive inhibition of LPS binding to toll-like receptor 4 (TLR4). Adult male Brown Norway rats (250-350g) were ventilated at low tidal volume (LTV, 7 ml/kg) or high tidal volume (HTV, 20 ml/kg) for 2 hrs, 85 breaths/min. A subset of animals received intravenous OxPAPC ( l .5mg/kg) at the start of mechanical ventilation. Bronchoalveolar lavage (BAL) cell count and protein concentration were measured as markers of inflammation and vascular permeability. EC monolayer barrier function in vitro was assessed by morphological analysis of agonist-induced gap formation. HTV caused a 70% increase in BAL total cell count (p <0.05) and a 169% in- crease in BAL protein (p < 0.01) compared with LTV controls. OxPAPC reduced HTV-induced elevations in total cell count (41% decrease vs. HTV alone) and protein (42% decrease vs. HTV alone). In vitro, high magnitude cyclic stretch (18% elongation) applied to lung EC increased thrombin-induced bar- rier dysfunction, whereas OxPAPC dramatically attenuated thrombin-induced EC disruption and enhanced EC recovery phase. These studies demonstrate for the first time the protective effect of oxidized phospholipids on ventilator induced lung inflammation and barrier dysfunction independent on TLR4- mediated inflammatory cascade. Supported by NIH grants HL75349, HL76259, HL58064

4868 We-Th, no. 39 (P64) Model ing pulmonary transport of l iquid plugs in microf lu id ic channels C. Ody, E. de Langre, C.N. Baroud. Laberateire d'Hydredynamique (LadHyX), Ecole Polytechnique, Palaiseau, France

Liquid plugs may be present in the lung either pathologically or for medication delivery. The transport of these plugs is complicated by the complex pattern of

$601

bifurcations in the pulmonary tree; for this reason, understanding the behavior of a plug at a bifurcation constitutes an important milestone in the modeling of lung airway re-opening. Modern microfluidic fabrication techniques allow us to make model systems consisting either of one bifurcation or a network of successive branchings. The typical length scales of the microfluidic channels also allow us to work in the range where capillary forces are dominant, thus modeling the small scales in the lung. We inject plugs of liquid of controlled length (L) into the microfluidic channel and observe the behavior as the plug reaches a bifurcation, driven by a constant pressure (P). The parameter space L-P may therefore be mapped experimentally. In a T-shaped bifurcation, we observe three main regimes with (a) the plug remaining trapped at the entrance of the bifurcation, (b) dividing into two daughter plugs in the daughter channels, or (c) popping and opening the channel to air flow. A physical model is developed to understand the three behavior regimes, based on a balance of capillary pressure-jumps and the driving pressure. The transition between regimes (b) and (c) is then explained by geometric arguments. For a Y-shaped bifurcation, the behavior also depends on the angle made by the daughter branches. For a sufficiently large angle, we recover the behavior found for the T junction, with a small correction due to the geometry. For small branching angles, we find that no threshold pressure exists. These studies are then applied to the study of a more complex network of successive bifurcations where the interest is geared towards the behavior of the complete network rather than of a single liquid plug.

5401 We-Th, no. 40 (P64) Three-component gas velocity mapping by magnetic resonance imaging

E. Durand 1 , L. de Rochefort 1 , X. Maltre 1 , R. Fodil 2, B. Louis 2, L. Vial 3, L. Darrasse 1 , G. Caillibotte 3, G. Sbirlea-Apiou 3, J. Bittoun 1 , D. Isabey 2. 1CNRS/Universit6 Paris-Sud (U2R2M-UMR8081), Bic~tre, France, 21NSERM, UMR 651; Universit~ Paris XIL Cr~teil, France, 3Air Liquide, Groupe Gaz M~dicaux, Les Loges en Josas, France.

In 1982, magnetic resonance imaging (MRI) was proposed to acquire velocity maps, by phase-encoding the signal emitted by hydrogen nuclei [1]. This "phase-contrast MRr' technique has been applied in liquids, mostly for blood flow acquisitions in vive [2]. MRI is neither limited to liquid state norto hydrogen. However, gas MRI was hindered by an inherent low nucleus density. In 1994, this limitation was overcome with hyperpolarised xenon and images on gas were acquired in mouse [3]. Since then, many studies have been reported with hyperpolarised gas imaging. Here, we report the combination of phase-contrast technique and hyperpo- larised helium-3 to acquire velocity maps of gas in a 1.5 T MRI device. Helium-3 (stable isotope) was hyperpolarised on-site by metastability-exchange optical pumping. It was then mixed with nitrogen and injected into various geometries promoting 3D-airway-like flows (straight, U-shaped, and bifurcation pipes). MRI velocity maps were acquired in a 1 cm thick slice and a field-of-view of 10 cm. In-plane pixel size was 1.6 mm. The three velocity components were acquired in about 1 s. Flows computed from integration of the measured velocities matched within 5% the input flows given by a mass flowmeter. Velocity maps also were found in good agreement for both the through-plane component and the secondary mo- tion with predicted velocities: either Poiseuille flow (straight pipe) or simulated 3D-flows (other). Finally, the feasibility in-vive was demonstrated in the trachea of a human volunteer. This technique proves reliable to map the three components of gas velocity, even through opaque walls and with no need for an external probe. Then, it can be used for experimental validation of numerical models in 3D-reconstructed geometries. It also opens an original way for airflow measurements in vive. Acknowledgements: Laboratoire Kastler Brossel (ENS) - Minist~re de la Recherche (RNTS01B0338)

References [1] Moran.Magn. Reson. Imag. 1982; 1: 197-203. [2] Dumoulin. Acta Radiol. Supp. 1986; 369: 17-20. [3] Albert. Nature 1994; 370: 199-201.

5549 We-Th, no. 41 (P64) Oscillatory flow in image-based bronchial airway model

G. Tanaka 1 , G. Inagaki 1 , M. Hishida 1 , H. Haneishi 2, X. Hu 3. 1Department of Electronics and Mechanical Engineering, Chiba University, Chiba, Japan, 2Research Center for Frontier Medical Engineering, Chiba University, Chiba, Japan, 3Fluent Asia Pacific Co. Ltd., Tokyo, Japan

Computational fluid dynamics (CFD) simulation was carried out for an oscil- latory flow in a 3-D realistic model of the human central airways, and the effect of airway geometry on the oscillatory flow stricture was revealed. The computational model of multi-branching airways was prepared from X-ray CT