$596 Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)

6215 We-Th, no. 14 (P64) Evaluation of nasal airway patency by analysis of breathing sounds U. Zaretsky 1 , D. Elad 1 , A. Primov-Fever 2, M. Wolf 2,3. 1Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel, 2Department of Otorhinolaryngology, Sheba Medical Center, Tel HaShomer, Israel, 3 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Acoustic signals have been used in medicine since early days, especially in the respiratory system. These signals represent the summation of sound waves which originate from the respiratory turbulent air flow and are also modified by the airway geometry and tissue characteristics. In a previous investigation we demonstrated the correlation between the energy of high frequency content and the degree of vessel obstruction. The goal of this study was to examine whether the content of nasal acoustic signals contains structures that may provide parameters to differentiate between obstructed and open nasal passageways. We developed a simple device with two condenser microphones that could be positioned on the external sides of the nostrils nearby the nasal nares. The subject was instructed to breathe through the nose for several cycles and efforts. Nasal decongestant was applied to the nose that yielded lower amplitudes and after 5 minutes the maneuver was repeated. The signals were amplified and digitized into the PC for off-line processing. Data processing was performed on the expiratory phase only and included averaging over three selected cycles, noise reduction and evaluation of the ratios of the sum of amplitudes (kPSD) and the sum of square amplitudes (kAMP) between the two sides of the nasal passageways. The data was recorded from 20 healthy volunteers who signed an informed consent. The analysis revealed that the kPSD parameter correlated well with the expected (i.e., treated) side in 14 out of the 20 examinees. Non-significant changes were noted in 4 examinees and changes in the opposite direction were found in 2 examinees. Subjective sensation was also recorded and have shown good correlation with the objective parameters in 45-65% of the subjects. In conclusion, a simple non-invasive test revealed a potential for quick and objective evaluation of differences between the nasal passageways patency.

6696 We-Th, no. 15 (P64) Mechanics of respiratory muscles in s ingle- lung transplanted emphysematic patients A. Ratnovsky 1, M.R. Kramer 2, D. Elad 1. 1Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel, 2pulmonary Institute, Rabin Medical Center, Petach Tikva, Israel

The efficiency of respiration depends on the coordinated movement of the respiratory muscles in generating sufficient pressure gradients for air flow in and out of the lungs. In hyperinflated lungs, such as in emphysema, the alteration in the geometry of the respiratory muscles decreases their ability to drive the respiratory pump. Single-lung transplantation (SLT) improves the qualify of life and exercise capacity of emphysematic patients, but it may induce asynchronous performance between the respiratory muscles on the two sides of the chest. Recently, we demonstrated that the electromyography (EMG) signals of four main respiratory muscles were without substantial differences between the healthy and emphysematic groups, and between the side of the transplanted lung and that of the native lung. However, the global strength of respiratory muscles as measured by mouth pressure was found to be significantly lower in the emphysematic group. In this study we investigated the effect of SLT in emphysema patients upon respiratory muscles mechanics. The forces and powers generated by three main respiratory muscles were calculated for a range of respiratory maneuvers in emphysematic patients with a single transplanted lung and were compared with the results of healthy sub- jects. The control group demonstrated significantly higher averaged maximal forces, work and power. The total work done by each respiratory muscle on the side of the transplanted lung was higher compared with that of the native lung side and compared with the control group. Taken together, these results suggested that he asynchrony between the lungs after single-lung transplant leads to asynchronous muscle forces and work as well as lesser muscle strength compared to healthy subjects.

6911 We-Th, no. 16 (P64) Surface tension distribution in lungs with surrfactant deficiency S. Ben-Zaken 1 , A. Marmur 2, Z. Weintraub 3, E. Kimmel 1 . 1Biomedical Engineering Department, Technion liT, Haifa, Israel, 2Chemical Engineering Department, Technion liT, Haifa, Israel, 3Neonatal Department, Western Galilee Hospital Nahariya, Medicine Department, Technion liT, Haifa, Israel

Lung surfactant is a surface active agent which appears in the liquid films that coat surfaces in the lung. Deficiency of surfactant in the lung induces pathological functioning such as in respiratory distress syndrome (RDS) in pre- mature newborns. Some 15 years ago, the dodecahedron model (Kimmel, E., and Budiansky, B.(1990): ASME J. Biomech. Eng. 112: 160-167) provided a theoretical framework that related mechanical properties of homogeneous lung

Poster Presentations

parenchyma, such as viscoelastic moduli, with surface tension, transpulmonary pressure and tensile forces in the tissue components. In this study we measure alveolar size and shape distribution in rat lungs using microscope pictures taken through the pleura by means of CSD camera which is mounted over an opening in the chest. The rat is intubated and ventilated and tracheal pressure is measured as well. Image analysis, using Image-pro +© software, provides size and shape distribution of alveoli in normal lung (n = 20); in washed lung (n = 15) that suffers from lack of surfactant (BAL); and in a lung (n = 10) that was first washed and then treated by exogenous surfactant (SRT). Images of alveoli were grouped and associated with inflation and deflation limbs. Dimensions such as maximal and minimal sizes, aspect ratio, area and average diameter of each alveolus were calculated. A novel method is suggested to estimate local surface tension in each alveolar size group, using the dodecahedron model. Increased level of spoil to lung surfactant is typified by: (i) a wider range of alveolar sizes where most of the open and active alveoli are greater in size than normal; ( i i ) increased surface tension from below 30dyne/cm in normal lung to about 70dyne/cm in BAL and (iii) decreased differences between inflation and deflation curves and therefore decreased hysteresis. The increased respiratory effort in RDS is probably not connected to the reduced hysteresis-like differences between inflation and deflation in the BAL lung compared to normal.

6981 We-Th, no. 17 (P64) The experimental evaluation of asymmetric ventilation waveforms on surfactant transport during airway reopening J.E. Pillert, D.P. Gaver II1. Biomedical Engineering Department, Tulane University, New Orleans, LA, USA

Acute Respiratory Distress Syndrome (ARDS) can be described as a decrease in pulmonary compliance with an accumulation of alveolar edema, leading to airway occlusion. Mechanical ventilation, while a common treatment for ARDS, is also known to result in low-volume ventilator-induced lung injury. The large mechanical stresses associated with ventilator-induced injury can lead to epithelial cell damage, further damaging a diseased lung. Our goal is to use this information to experimentally study the mechanics and surfactant adsorption at the air-liquid interface and identify optimized ventilation parameters. In this study, a rigid model of airway reopening, consisting of a narrow-bore (1 mm ID) glass tube maintained at 37°C, is utilized to explore the effects of an asymmetric ventilation waveform at an air-liquid interface on surfactant transport. A finger of air is oscillated and progressed through purified H20 or a surfactant-doped solution and the capillary pressure drop across the a i r - liquid interface is determined. This simplified model of an airway provides a means of evaluating waveform parameters (frequency, amplitude, mean flow, and degree of asymmetry) to reduce mechanical stresses that may damage the lungs during ventilation. Two general waveform asymmetries are studied: a fast-reverse flow, where the interface moves slower into the liquid occlusion relative to its faster motion back into the finger of air, and a fast-forward flow, where the asymmetric motion is reversed. The specific waveform parameters listed above are investigated with multiple values for both the fast-reverse and fast-forward degrees of asymmetry. A fast-reverse ventilation waveform is determined to be more successful at lowering capillary pressures than a fast-forward waveform. We hypothesize that during fast-reverse flow, surfactant builds up on the interface, providing a reservoir as the interface expands during its slow-forward flow. It is anticipated that identifying optimized waveforms will reduce low-volume ventilator-induced lung injury in patients with ARDS and other respiratory diseases. Supported by NASA grant NAG3-2734 and NIH P20-EB001432

6991 We-Th, no. 18 (P64) A computational model of the effects of airway reopening on the integrity of pulmonary epithelial tight junctions A.-M. Jacob, D.P. Gaver. Biomedical Engineering Department, Tulane University, New Orleans, LA, United States of America

Normal lung physiology is characterized by an intact, selective barrier function that permits the communication only of essential gases between the lungs and surrounding vessels. This is due in large part to the extremely low permeability of the pulmonary epithelial cell layer, which is established and maintained by the diffuse expression of tight junctions (TJs) between adjacent epithe- lial cells. Acute respiratory distress syndrome (ARDS) is the life-threatening pathology initiated by damage to the epithelium that causes the breakdown of this barrier and the flooding of the airways and alveoli with protenaceous edema fluid. Mechanical ventilation, though in most cases a necessary medical intervention, typically exacerbates this condition. Our analysis computationally examines this effect by determining the mechanical stresses that the epithelial cell layer experiences as air is forced into a liquid-filled edematous airway. Using finite element analysis, we examine how the apical fluid stresses - determined using the boundary element method - are transduced to the TJs

Track 13. Respiratory Mechanics

between neighboring cells and to basolateral contact sites with the underlying extracellular matrix. Our results, which depend on these epithelial structural connections as well as the internal mechanical properties of the cells and the stress environment of the airway, demonstrate the mechanical factors with the most significant influence on epithelial paracellular permeability. Supported by NASA NAG3-2734, NIH P20-EB001432

6127 We-Th, no. 19 (P64) Long-term cyclic stretch diminishes surfactant secretion in alveolar type II epithelial cells

S.P. Arold 1 , E. Bartol~k-Suki 2, B. Suki 1 . 1Dept. efBiemedical Engineering, Boston Univeristy, Boston, MA, USA, 2Aeris Therapeutic Inc. Wobum, MA, USA

Surfactant, a lipoprotein mixture secreted by alveolar epithelial type II (AEII) cells that line the surface of the lung, lowers surface tension at the alveolar air- liquid interface. During acute lung injury (ALl) pulmonary surfactant is deficient and/or non-functional increasing the probability of atelectasis and ventilator induced lung injury resulting from overexpansion of non-collapsed units or shearing forces due to airway/alveolar reopening. It has been demonstrated in cell culture that a single stretch enhances surfactant secretion in rat AEII cells grown on a flexible membrane, however little work has been done on the long-term effects of cyclic stretching on surfactant secretion. In this study we isolated rat AEII cells and cultured these cells on fibronectin coated, silastic membranes. These cells were exposed to 15, 30 or 60 minutes of sinusoidal biaxial stretch at 3 cycles per minute with an average magnitude of 12.5%, 25% or 50% change in membrane surface area. Following stretch we assayed the cells and media for labeled 3H phoshatidylcholine (PC) and conducted western blots for surfactant protein B (SP-B). We found that after 15 minutes of cyclic stretch, these cells demonstrated enhanced surfactant secretion at high strain and little change in secretion at lower levels of strain in comparison with that of unstretched control cells. Unexpectedly, we found that after 30 and 60 minutes of stretch there was more PC and SP-B in the media of unstretched control cells than those that underwent 25% or 50% cyclic stretch. Additionally, cells exposed to stretch had larger intra-cellular stores of both PC and SP-B suggesting a complex time and stretch pattern dependent regulation of surfactant secretion. These data may have implications for long- term mechanical ventilation strategies in the setting of ALl.

7237 We-Th, no. 20 (P64) Evolution of oscil latory mechanics in a two-week murine model of bleomycin-induced lung injury: a case control study M. Pinart 1 , A. Serrano 2, O. Bulbena 2, P.V. Romero 1 . 1Laboratory ef Experimental Pneumology, IDIBELL, L'Hospitalet, Barcelona, Spain, 2Department of Experimental Pathology, IIBB-CSIC, IDIBAPS, Barcelona., Spain

Bleomycin-induced pulmonary fibrosis is a useful model of disordered lung reparation. Mechanical properties and evolution of this model are insufficiently characterised. With this purpose, we have studied a total number of 134 adult male Sprague-Dawley rats, divided into two matched case-control groups. Rats were instilled with 0.25 U/100g body weight bleomycin or saline, and studied by pairs at the 3rd, 7th, and 15th day after instillation (N=22, 23, and 22 pairs respectively). Animals were anaesthetised, tracheotomised, mechanically ventilated, paralysed, and chest opened. Lung mechanics was studied by applying a composite wave of five equal amplitude discrete frequencies ranging between 0.2 and 3.1 Hz. Hydroxyprolin (HP) and Myeloperoxidase (MPO) concentrations in lung tissue were determined in freezed samples. By com- paring the bleomycin to matched controls, the results showed: (a) an increase of elastance since day 3 at all frequencies; (b) an increase of viscoelastic resistance at all frequencies at the 3rd day progressively decreasing in days 7 and 15; (c) no significant changes regarding hysteresivity except at day 15. HP increased at days 7 and 15, and MPO increased since day 3. By con- sidering the full population (N = 134), significant correlations were observed between HP and elastance at all frequencies, and MPO and hysteresivity at low frequencies. By conclusion: according to our results, bleomycin induces mechanical changes standing 15 days after instillation. Those changes reflect inflammatory and fibrinogenic processes. Resistance and hysteresis seem to be related to inflammatory changes, while elastance reflects mainly the fibrinogenic process.

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7230 We-Th, no. 21 (P64) Regional assessment of pulmonary function during forced maneuvers using MRI-based spirometry

A. Voorhees 1 , R.M. Goldring 2, K.I. Berger 2, Q. Chen 1 . 1Center ferBiemedical Imaging, Department of Radiology, New York University School of Medicine, USA, 2Department of Medicine, New York University School of Medicine, USA

A real-time magnetic resonance imaging (MRI) technique was developed and optimized for dynamic measurements of the lung parenchyma during forced maneuvers. Post-processing algorithms were developed to allow time-resolved tracking of the lung parenchyma from the MR images, providing the means for both global and local assessment of mechanical function of the lung. It is generally understood that regional differences in function do exist in the lungs and, in fact, a number of conditions (e.g. acute respiratory distress syndrome and status asthmaticus) can be characterized by local impairment. Lung function is clinically assessed largely using conventional spirometry, which is incapable of providing a regional diagnosis. Non-invasive techniques for examining mechanical function of the lung on a regional basis remain allusive. A class of high-temporal resolution MRI techniques was developed for lung imaging with high-temporal resolution and good signal-to-noise ratio. For this study, acquisition of a battery of breathing maneuvers, including forced expiration, was made possible using a turboFLASH sequence in combination with parallel imaging. The frame rate achieved was ten frames or images per second. Two-dimensional measurements were made in both coronal and sagital slice orientations. From the MR images, an automated segmentation routine was used to identity the chest wall/lung boundary, from which total lung volume was calculated and plotted as function of time. The MRI-derived lung volumes were validated by conducting simultaneous MRI and spirometry, which showed excellent agreement. A motion-tracking algorithm was developed for calculating local displacement of the lung parenchyma. Regional volumetric strain, or volume change reflecting ventilation, was calculated by taking the Jacobian determinant of the displacement map. Flow-volume loops, which aid in the localization of airway obstruction, were constructed on a regional basis allowing the means for regional assessment of pulmonary function.

7455 We-Th, no. 22 (P64) Assessing respiratory mechanics in obstructive diseases by forced oscil lation technique: importance of expiratory flow-limitation (EFL) R.L. Dellaca. Dipartimento di Bioingegneria, Politecnico di Milano University, Milano, Italy

In obstructive diseases airway choke points leading to EFL can occur even during spontaneous breathing. During EFL, flow across choke points is in- dependent of the driving pressure, and therefore choke points behave as if they were closure in response to forced oscillations. In these conditions measurements of input impedance (Zin) would reflect only the mechanical properties of the airways between the airway opening and choke points. We modeled expiratory Zin with a simple model consisting of a resistance (R), compliance (C) and inertance in series. This model would be invalid for obstructed patients without EFL (due to heterogeneity) but valid for patients with EFL only during expiration. In this case, the model represents the airways between the mouth and choke points. We studied 54 COPD patients during quiet breathing while applying pressure forcing with components at 5, 11 and 19 Hz to their mouth before and 45 min after bronchodilation. From flow and pressure at the mouth we estimated the time course of Zin. For each subject we selected -10 breaths, computed the average of Zin during each inspiration and expiration and used these to estimate model parameters. EFL was detected as in ERJ2004; 23: 232-240. Twenty-two patients showed EFL. The overall regression coefficient (r 2) was 0.44±0.25 during inspiration and 0.52±0.34 during expiration but, dividing flow- limited from non-flow-limited patients, r 2 was 0.35±0.22 and 0.51±0.24 dur- ing inspiration and 0.80±0.18 and 0.31±0.28 during expiration, respectively. Inspiratory-R was 4.2±1.3 cmH20 s/L in flow-limited and 4.0±1.2 cmH20 s/L in non-flow-limited patients. It was significantly different compared to expiratory-R only in non-flow-limited patients (4.9±1.5 cmH2Os/L, p <0.001). During EFL, C was 0.0033±0.0009 L/cmH20, a value smaller than expected, suggesting that it reflects airway wall compliance rather than tissues. Bronchodilation affected significantly only the inspiratory parameters, mainly by reducing R. Consistent with our hypothesis, the simple series model fit data well only during expiration with EFL in COPD patients. As both EFL and inspiratory-expiratory phases affect significantly Zin, the clinical interpretation of FOT data should include within-breath analysis and detection of EFL.