Pressure oscillation delivery to the lung: Computer simulation of neonatal breathing parameters

Preterm newborn infants may develop respiratory distress syndrome (RDS) due to functional and structural immaturity. A lack of surfactant promotes collapse of alveolar regions and airways such that newborns with RDS are subject to increased inspiratory effort and non-homogeneous ventilation. Pressure oscillation has been incorporated into one form of RDS treatment; however, how far it reaches various parts of the lung is still questionable. Since in-vivo measurement is very difficult if not impossible, mathematical modeling may be used as one way of assessment. Whereas many models of the respiratory system have been developed for adults, the neonatal lung remains essentially ill-described in mathematical models. A mathematical model is developed, which represents the first few generations of the tracheo-bronchial tree and the 5 lobes that make up the premature ovine lung. The elements of the model are derived using the lumped parameter approach and formulated in Simulink? within the Matlab? environment. The respiratory parameters at the airway opening compare well with those measured from experiments. The model demonstrates the ability to predict pressures, flows and volumes in the alveolar regions of a premature ovine lung.     

A gross and microscopic study of the respiratory anatomy of the Antarctic Weddell seal, Leptonychotes weddelli.

Four species of Phocidae, or true seals, inhabit the waters surrounding the Antarctic continent. These animals are thought to have different diving capabilities. The Weddell seal, Leptonychotes weddelli, is known to be capable of attaining depths up to 600 meters. The respiratiory system of the Weddell seal shows the usual adaptations to an aquatic environment characteristic of other marine. These include lungs that undergo compression acollapse at depths greater than 70 meters; hyaline cartilage in the tracheo-bronchial tree as far as the terminal bronchioles; and large amounts of smooth muscle surrounding the distal-most bronchioles. The collapsible lungs provide a mechanism by which air is forced from the alveoli adjacent to the pulmonary capillary beds thereby preventing the absorption of nitrogen gas into the bloodsteam. The presence of hyaline cartilage throughout most of the tracheo-bronchial tree increases the effective dead air space that accommodates most of the air forced from the collapsed lungs. The smooth muscle surrounding the respiratory bronchioles prevents their collapse while under the pressures of a deep dive. Collapse of the respiratory bronchioles not supported by cartilage would trap air in the lung alveoli during a dive. In addition, large- sac-like "diverticulae" are found in the submucosa throughout the tracheo-bronchial tree. These diverticulae, which open directly into the lumen of the tree, appear to be modified glands whose cells, in most cases, do not appear to be specialized for secretory function. They are most numerous in the more distal bronchi and terminal bronchioles where they are situated on both the luminal and adventitial sides of the hyaline cartilage supporting the walls of the air passages. Diverticulae are not found in the respiratory bronchioles or in the respiratory portion of the lungs.     

Functional localization of pulmonary stretch receptors in the airways of the cat

During a respiratory effort against a closed airway the afferent activity of vagal fibres from pulmonary stretch receptors does not appreciably increase during the inspiratory phase because the lung is prevented from expanding. The possibility to perform occlusions at different levels of the airways allows the localization of pulmonary stretch receptors in the tracheo-bronchial tree. 100 fibres from pulmonary stretch receptors of the left and right sides of the tracheo-bronchial tree have been studied in 3 cats and their localization found as follows: 10% in the higher half of the intrathoracic trachea, 22% in the lower half of the intrathoracic trachea and the carina, 7% in the main bronchus and 61% in the intrapulmonary airways. Knowing the surface area of the tracheo-bronchial tree at different levels and assuming total of 1200 stretch receptors from each side their average concentration resulted as follows: 50.0 receptors/cm2 in the higher half of the intrathoracic trachea, 108.0/cm2 in the lower half of the intrathoracic trachea and the carina, 213.0/cm2 in the main bronchus and 1.3/cm2 in the intrapulmonary airways.     

Effect of tidal volume and PEEP in ethchlorvynol-induced asymmetric lung injury.

We examined the effects of positive end-expiratory pressure (PEEP) and tidal volume on the distribution of ventilation and perfusion in a canine model of asymmetric lung injury. Unilateral right lung edema was established in 10 animals by use of a selective infusion of ethchlorvynol. Five animals were tested in the supine position (horizontal asymmetry) and five in the right decubitus position (vertical asymmetry). Raising PEEP from 5 to 12 cmH2O improved oxygenation despite a redistribution of blood flow toward the damage lung and a consistent decrease in total respiratory system compliance. This improvement paralleled a redistribution of tidal ventilation to the injured lung. This was effected primarily by a fall in the compliance of the noninjured lung due to hyperinflation. The effects of higher tidal volume were additive to those of PEEP. We propose that the major effect of PEEP in inhomogeneous lung injury is to restore tidal ventilation to a population of alveoli recruitable only at high airway pressures.     

Distribution of pulmonary ventilation using Xe-enhanced computed tomography in prone and supine dogs.

Xe-enhanced computed tomography (CT; Xe-CT) is a method for the noninvasive measurement of regional pulmonary ventilation in intact subjects, determined from the washin and washout rates of the radiodense, nonradioactive gas Xe, as measured in serial CT scans. We used the Xe-CT ventilation method, along with other quantitative CT measurements, to investigate the distribution of regional lung ventilation and air content in healthy, anesthetized, mechanically ventilated dogs in the prone and supine postures. Vertical gradients in regional ventilation and air content were measured in five mongrel dogs in both prone and supine postures at four axial lung locations. In the supine position, ventilation increased with dependent location, with a mean slope of 7.3%/cm lung height, whereas no ventilation gradients were found at any location in the prone position. These results agree quantitatively with other published studies. In addition, six different animals were studied (3 supine, 3 prone) to examine the longitudinal distribution of ventilation and air content. The prone lungs were more uniformly inflated compared with the supine, which were less well expanded at the base than apex. Ventilation index, a measure of regional ventilation relative to whole lung ventilation, increased steeply from apex to base in the supine animals, whereas it was again more uniform in the prone condition. We conclude that the Xe-CT method provides a reasonable, quantitative measurement of regional ventilation and promises to be a valuable tool for the noninvasive determination of regional lung function.     

Simulation of Pulmonay Damages Induced by Inhaled CL2 on the Bronchial Tree

We have measured the change of lung mechanical parameters on isolated rabbit lungs exposed to chlorine gas (Cl{in2}). Experimental results show parallel increase in elastance and resistance of impaired lungs. We tried to determine whether this may be explained by a reduction of the ventilated areas in the lung, consecutive to closure of some airways. We have then tried to simulate these experimental results by studying the effects of various airways occlusions imposed on two concurrent models (symmetrical and dissymmetrical) of the tracheo-bronchial tree. For each model, we successively evaluated the resistance of the normal lung, simulated a partial peripheral airways occlusion and estimated the induced changes in total resistance. Analytical expressions of the "occluded lung" elastance and resistance have been found for the symmetrical model but not for the dissymmetrical model (a graphical approach is proposed). With the symmetrical model, simulated results are comparable to experimental ones when the occlusion level is proximal. Whatever the dissymmetry level (δ) of the fractal tree model, we could not simulate the expected increase in resistance with the observed increase in elastance. We conclude that either the occlusion is non homogeneous or the lung impairment is not only a reduction in ventilated areas. This revised version was published online in June 2006 with corrections to the Cover Date.     

Distribution of regional lung aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury

In acute lung injury (ALI), pressure support ventilation (PSV) may improve oxygenation compared with pressure-controlled ventilation (PCV), and benefit from random variation of pressure support (noisy PSV). We investigated the effects of PCV, PSV, and noisy PSV on gas exchange as well as the distribution of lung aeration and perfusion in 12 pigs with ALI induced by saline lung lavage in supine position. After injury, animals were mechanically ventilated with PCV, PSV, and noisy PSV for 1 h/mode in random sequence. The driving pressure was set to a mean tidal volume of 6 ml/kg and positive end-expiratory pressure to 8 cmH?O in all modes. Functional variables were measured, and the distribution of lung aeration was determined by static and dynamic computed tomography (CT), whereas the distribution of pulmonary blood flow (PBF) was determined by intravenously administered fluorescent microspheres. PSV and noisy PSV improved oxygenation and reduced venous admixture compared with PCV. Mechanical ventilation with PSV and noisy PSV did not decrease nonaerated areas but led to a redistribution of PBF from dorsal to ventral lung regions and reduced tidal reaeration and hyperinflation compared with PCV. Noisy PSV further improved oxygenation and redistributed PBF from caudal to cranial lung regions compared with conventional PSV. We conclude that assisted ventilation with PSV and noisy PSV improves oxygenation compared with PCV through redistribution of PBF from dependent to nondependent zones without lung recruitment. Random variation of pressure support further redistributes PBF and improves oxygenation compared with conventional PSV.     

Modeling stochastic and spatial heterogeneity in a human airway tree to determine variation in respiratory system resistance

Asthma is a variable disease with changes in symptoms and airway function over many time scales. Airway resistance (Raw) is variable and thought to reflect changes in airway smooth muscle activity, but just how variation throughout the airway tree and the influence of gas distribution abnormalities affect Raw is unclear. We used a multibranch airway lung model to evaluate variation in airway diameter size, the role of coherent regional variation, and the role of gas distribution abnormalities on mean Raw (Raw) and variation in Raw as described by the SD (SDRaw). We modified an anatomically correct airway tree, provided by Merryn Tawhai (The University of Auckland, New Zealand), consisting of nearly 4,000 airways, to produce temporal and spatial heterogeneity. As expected, we found that increasing the diameter variation by twofold, with no change in the mean diameter, increased SDRaw more than fourfold. Perhaps surprisingly, Raw was proportional to SDRaw under several conditions-when either mean diameter was fixed, and its SD varied or when mean diameter varied, and SD was fixed. Increasing the size of a regional absence in gas distribution (ventilation defect) also led to a proportionate increase in both Raw and SDRaw. However, introducing regional dependence of connected airways strongly increased SDRaw by as much as sixfold, with little change in Raw. The model was able to predict previously reported Raw distributions and correlation of SDRaw on Raw in healthy and asthmatic subjects. The ratio of SDRaw to Raw depended most strongly on interairway coherent variation and only had a slight dependence on ventilation defect size. These findings may explain the linear correlation between variation and mean values of Raw but also suggest that regional alterations in gas distribution and local coordination in ventilation amplify any underlying variation in airway diameters throughout the airway tree.     

Regional ventilation during spontaneous breathing and mechanical ventilation in dogs

We evaluated the effects of the different patterns of chest wall deformation that occur with different body positions and modes of breathing on regional lung deformation and ventilation. Using the parenchymal marker technique, we determined regional lung behavior during mechanical ventilation and spontaneous breathing in five anesthetized recumbent dogs. Regional lung behavior was related to the patterns of diaphragm motion estimated from X-ray projection images obtained at functional residual capacity (FRC) and end inspiration. Our results indicate that 1) in the prone and supine positions, FRC was larger during mechanical ventilation than during spontaneous breathing; 2) there were significant differences in the patterns of diaphragm motion and regional ventilation between mechanical ventilation and spontaneous breathing in both body positions; 3) in the supine position only, there was a vertical gradient in lung volume at FRC; 4) in both positions and for both modes of breathing, regional ventilation was nonlinearly related to changes in lobar and overall lung volumes; and 5) different patterns of diaphragm motion caused different sliding motions and differential rotations of upper and lower lobes. Our results are inconsistent with the classic model of regional ventilation, and we conclude that the distribution of ventilation is determined by a complex interaction of lung and chest wall shapes and by the motion of the lobes relative to each other, all of which help to minimize distortion of the lung parenchyma.     

Mechanical and gas-distribution behavior of a collateral ventilation model

We extended the theoretical analysis of Otis et al. (J. Appl. Physiol. 8: 427-443, 1956) to study the effects of collateral ventilation on lung mechanics and gas distribution. Equations were developed to express the effective compliance, the effective resistance, and the distribution of airflow and tidal volume in a two-compartment model incorporating a collateral communication. The analysis of the model showed that, in general, collateral ventilation tends to attenuate the degree of frequency dependence of compliance and resistance, the magnitude of this effect being dependent on the mechanical properties of the model, including collateral resistance. The influence of collateral ventilation is important when the model simulates the mechanical characteristics of the emphysematous lung (marked time-constant inequality with regionally high airway resistance, and relatively low collateral resistance). Under these conditions, a large fraction of the tidal volume of the high airway resistance lung compartment is contributed by the collateral communication. The effects of collateral ventilation on the mechanical behavior of the model are negligible when collateral resistance largely exceeds airway resistance (simulating experimental findings in normal lungs). The present theoretical data suggest that the use of equations based on a model incorporating collateral ventilation is justified, at least in predicting the mechanical and gas-distribution behavior of the lung in emphysema.     

Ventilation distribution in rats: Part 2 -- A comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

ABSTRACT: BACKGROUND: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. METHODS: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. RESULTS: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. CONCLUSION: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.     

Relationships between the lung clearance index and conductive and acinar ventilation heterogeneity

The lung clearance index (LCI) derived from a multiple breath washout test has regained considerable popularity in recent years, alternatively being promoted as an early detection tool or a marker of small airways function. In this study, we systematically investigated the link between LCI and indexes of acinar and conductive airways ventilation heterogeneity (Sacin, Scond) to assess potential contributions from both lung zones. Relationships were examined in 55 normal subjects after provocation, where only Scond is known to be markedly increased, and in 55 asthma patients after bronchodilation, in whom both Scond and Sacin ranged between normal and abnormal. LCI was correlated to Scond in both groups (R = 0.37-0.43; P < 0.01 for both); in the asthma group, LCI was also tightly correlated to Sacin (R = 0.70; P < 0.001). Potential mechanisms operational at various levels of the bronchial tree were identified by considering washout curvilinearity in addition to LCI to distinguish specific ventilation and dead space effects (also illustrated by simple 2-compartment model simulations). Although the asthma data clearly demonstrate that LCI can reflect very peripheral ventilation heterogeneities, the normal provocation data also convincingly show that LCI increases may be the exclusive result of far more proximal ventilation heterogeneities. Because LCI potentially includes heterogeneities at all length scales, it is suggested that ventilation imaging in combination with LCI measurement at the mouth could identify the scale of relevant ventilation heterogeneities. In the meantime, interpretations of LCI results in the clinic based on washout curves collected at the mouth should be handled with caution.     

Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung.

The classic four-zone model of lung blood flow distribution has been questioned. We asked whether the effect of positive end-expiratory pressure (PEEP) is different between the prone and supine position for lung tissue in the same zonal condition. Anesthetized and mechanically ventilated prone (n = 6) and supine (n = 5) sheep were studied at 0, 10, and 20 cm H2O PEEP. Perfusion was measured with intravenous infusion of radiolabeled 15-microm microspheres. The right lung was dried at total lung capacity and diced into pieces (approximately 1.5 cm3), keeping track of the spatial location of each piece. Radioactivity per unit weight was determined and normalized to the mean value for each condition and animal. In the supine posture, perfusion to nondependent lung regions decreased with little relative perfusion in nondependent horizontal lung planes at 10 and 20 cm H2O PEEP. In the prone position, the effect of PEEP was markedly different with substantial perfusion remaining in nondependent lung regions and even increasing in these regions with 20 cm H2O PEEP. Vertical blood flow gradients in zone II lung were large in supine, but surprisingly absent in prone, animals. Isogravitational perfusion heterogeneity was smaller in prone than in supine animals at all PEEP levels. Redistribution of pulmonary perfusion by PEEP ventilation in supine was largely as predicted by the zonal model in marked contrast to the findings in prone. The differences between postures in blood flow distribution within zone II strongly indicate that factors in addition to pulmonary arterial, venous, and alveolar pressure play important roles in determining perfusion distribution in the in situ lung. We suggest that regional variation in lung volume through the effect on vascular resistance is one such factor and that chest wall conformation and thoracic contents determine regional lung volume.     

Ventilation-perfusion distribution and shunt fraction during one-lung ventilation: effect of different inhaled oxygen levels

Ventilation with higher fraction of inspired oxygen (F(I)O2) is one of the commonly-chosen strategies executed for treatment of hypoxemia during one lung ventilation (OLV) for thoracic surgery. In this study, we investigated the effect of F(I)O2 on pulmonary ventilation-perfusion (VA/Q) distribution during OLV. Six pigs, weighing 27 to 34 kg, were selected for this study. Following by a steady-state period, randomized administrations of F(I)O2 with 0.4, 0.6 and 1.0 were performed for 30 minutes at the right lateral decubitus position during OLV, while hemodynamic data and lung mechanics were simultaneously monitored. The VA/Q distributions of the lung(s) were assessed by the multiple inert gas elimination technique (MIGET). PaO2 at F(I)O2 of 100% was significantly reduced in OLV compared with two-lung ventilation (TLV) (522 +/- 104 vs. 653 +/- 21 mmHg; P < 0.001) at right lateral decubitus position. MIGET algorithms demonstrated a wider VA/Q distribution during OLV at F(I)O2 of 40%, as compared with distribution during TLV at F(I)O2 of 100%, but a bimodal perfusion distribution shifted to lower VA/Q component during OLV at F(I)O2 of 100%. There was an increase of pulmonary shunting in OLV, as compared with TLV at F(I)O2 of 100% (1.94 +/- 2.2% vs. 9.5 +/- 9.7%; P < 0.01). In addition, OLV caused a significant increase in the dispersion of perfusion at F(I)O2 of 100% (0.62 +/- 0.20 vs. 0.44 +/- 0.23; P < 0.01), but ventilation showed no denoting changes (1.06 +/- 0.20 vs. 0.98 +/- 0.35; P > 0.01). During OLV with right lateral decubitus position, there were no significant changes in the pulmonary shunt, the dispersion of perfusion and ventilation at different F(I)O2. OLV resulted in an increase in pulmonary shunting and heterogeneity compared with TLV. Furthermore, the PaO2 decreased during OLV regardless of the postural changes. At different F(I)O2, there were no significant changes in the pulmonary shunt, the dispersion of perfusion and ventilation during OLV with right lateral decubitus posture.     

Cardiorespiratory effects of heliox using a model of upper airway obstruction]

Heliox is a mixture of Oxygen and Helium. The low density of Helium allows this mixture to flow in a laminar pattern where oxygen, nitrogen or air flow would be turbulent. Therefore the force necessary to move a volume of gas (e.g. Heliox) is greatly reduced in comparison to a turbulent gas flow. In a respiratory loading experiment we investigated the effects which Heliox exerts on hemodynamic as well respiratory variables. 10 volunteers were breathing spontaneously and through three different endotracheal (ET-) tubes (ID 4.0, 4.5, 5.0 mm).The subjects were switched from room air to Heliox and differences in the variables heart rate (HR), blood pressure (BP), stroke volume (SV), stroke index (SI), peripheral vascular resistance (TPRI) and left ventricular work index (LVWI) were measured. Furthermore the (PhAng) between abdomen and thorax was detected using respiratory inductance plethysmography (n=2) and the sense of dyspnoe under the different conditions was assessed by the use of a dyspnea score (DS). The means of BP, SV, SI, TPRI and LVWI did not significantly differ between the resting and the different loading conditions irrespective of the gas that was used. The variability of hemodynamic measures was significant larger during loaded vs. unloaded breathing. Heliox could significantly reduce this degree of variability. In two subjects Heliox could also significantly reduce the PhAng as well as DS. Heliox showed effects on hemodynamic as well as respiratory and subjective variables. These effects can be interpreted as a reduction of the extent of pressure variations in the intrapleural space leading to less impact on hemodynamic variables while breathing Heliox vs. room air in a resistive loading experiment. In the future the combined measurement of hemodynmic variables as well as non-invasive assessment of respiration might shed new light on cardio-respiratory interaction and effects of Heliox during airway obstruction.     

Topographical distribution of pulmonary perfusion and ventilation, assessed by PET in supine and prone humans.

Using positron emission tomography (PET) and intravenously injected (13)N(2), we assessed the topographical distribution of pulmonary perfusion (Q) and ventilation (V) in six healthy, spontaneously breathing subjects in the supine and prone position. In this technique, the intrapulmonary distribution of (13)N(2), measured during a short apnea, is proportional to regional Q. After resumption of breathing, regional specific alveolar V (sVA, ventilation per unit of alveolar gas volume) can be calculated from the tracer washout rate. The PET scanner imaged 15 contiguous, 6-mm-thick, slices of lung. Vertical gradients of Q and sVA were computed by linear regression, and spatial heterogeneity was assessed from the squared coefficient of variation (CV(2)). Both CV and CV were corrected for the estimated contribution of random imaging noise. We found that 1) both Q and V had vertical gradients favoring dependent lung regions, 2) vertical gradients were similar in the supine and prone position and explained, on average, 24% of Q heterogeneity and 8% of V heterogeneity, 3) CV was similar in the supine and prone position, and 4) CV was lower in the prone position. We conclude that, in recumbent, spontaneously breathing humans, 1) vertical gradients favoring dependent lung regions explain a significant fraction of heterogeneity, especially of Q, and 2) although Q does not seem to be systematically more homogeneous in the prone position, differences in individual behaviors may make the prone position advantageous, in terms of V-to-Q matching, in selected subjects.     

Effect of lung inflation on regional lung expansion in supine and prone rabbits

At functional residual capacity, lung expansion is more uniform in the prone position than in the supine position. We examined the effect of positive airway pressure (Paw) on this position-dependent difference in lung expansion. In supine and prone rabbits postmortem, we measured alveolar size through dependent and nondependent pleural windows via videomicroscopy at Paw of 0 (functional residual capacity), 7, and 15 cmH2O. After the chest was opened, alveolar size was measured in the isolated lung at several transpulmonary pressures (Ptp) on lung deflation. Alveolar mean linear intercept (Lm) was measured from the video images taken in situ. This was compared with those measured in the isolated lung to determine Ptp in situ. In the supine position, the vertical Ptp gradient increased from 0.52 cmH2O/cm at 0 cmH2O Paw to 0.90 cmH2O/cm at 15 cmH2O Paw, while the vertical gradient in Lm decreased from 2.17 to 0.80 microns/cm. In the prone position, the vertical Ptp gradient increased from 0.06 cmH2O/cm at 0 cmH2O Paw to 0.35 cmH2O/cm at 15 cmH2O Paw, but there was no change in the vertical Lm gradient. In anesthetized paralyzed rabbits in supine and prone positions, we measured pleural liquid pressure directly at 0, 7, and 15 cmH2O Paw with dependent and nondependent rib capsules. Vertical Ptp gradients measured with rib capsules were similar to those estimated from the alveolar size measurements. Lung inflation during mechanical ventilation may reduce the vertical nonuniformities in lung expansion observed in the supine position, thereby improving gas exchange and the distribution of ventilation.     

Dynamic model of the bronchial tree

We present a distributed model of the bronchial tree which simulates the global dynamic characteristics of the lung. Local mechanical characteristics of each airway are represented by RCL circuits and parameters of the electrical components are determined from local physiological data. The bronchi geometry is described by Weibel's symmetric model, the flow in each airway is assumed laminar and mixing effects at the bifurcations are neglected; the transpulmonary pressure is assumed to be sinusoidal. In simulations of quiet breathing the resistance to airflow is found to be dominant, the flow amplitude decreasing as breathing frequency increases, but remaining almost constant in all the generations. Simulations of ventilation through obstructed lungs show frequency dependence of the dynamic characteristics in very compliant lungs. The global resistance to airflow and the dynamic compliance of the bronchi decrease as the forced oscillation frequency increases in a pattern similar to in vivo measurements in diseased lungs. This may be an outcome of the RCL properties of the network rather than due to uneven distribution of mechanical properties of the lung.     

Is tryptophan catabolism increased under indoleamine 2,3 dioxygenase activity during chronic lung inflammation in pigs?

In a preliminary study we observed that piglets suffering from chronic lung inflammation induced by an intravenous injection of complete Freund adjuvant showed a marked decrease in plasma tryptophan (Trp) concentration suggesting increased Trp utilisation. During the inflammatory process, a cytokine-induced enzyme called indoleamine 2,3-dioxygenase (IDO) has been shown to catabolise Trp into kynurenine (Kyn). Yet, during inflammation, increased Trp catabolism may decrease Trp availability for other functions such as growth. This metabolic pathway has never been studied in pigs. So, the objectives of this study were to measure IDO activity in pigs and to determine if the decrease in plasma Trp concentrations previously observed in piglets suffering from chronic lung inflammation could be explained by the induction of IDO activity. In order to do so, we compared IDO activity measured in the tracheo-bronchial lymph nodes and in the lungs of 7 piglets, injected with complete Freund adjuvant (CFA), to 7 pair-fed littermate healthy controls. Blood samples were taken at 0, 2, 5, 7 and 10 days following CFA injection in order to measure plasma Trp, Kyn and haptoglobin concentrations. Indoleamine 2,3-dioygenase activity in the tracheo-bronchial lymph nodes (P < 0.05), in the lungs (P < 0.07) and plasma haptoglobin (P < 0.01) were higher in pigs with lung inflammation than in the controls. Plasma Trp and Kyn were not significantly affected by CFA injection. Our data showed that IDO is activated under chronic lung inflammation in pigs. The impact of IDO activation on plasma Trp concentration and its availability is discussed according to the amount of Trp provided by the diet.