SIMULATIONS OF SURFACTANT DELIVERY IN RAT, PIG, AND HUMAN PULMONARY AIRWAYS SYSTEMS 

Get Complete Project Material File(s) Now! »

Effect of inertia and gravity on liquid plug splitting at a bifurcation

In 200 6, Zheng et al. [136] set up a n experim ent to ass ess the ef ect of inertia and gravity on liquid plug splitting at a bifurcation individually. The sizes and dim ensions of the setup were similar to their experiment used for compariso n in the previous section [82]. The main dife rence between these two studies consiste d of investigating the efect of inertia. In thei r experimental results, they presented Rs vs. ReP for various experimental conditions. ReP ranged from 5 to 300 while the capilla ry numbe r varied between 2 10-5 a nd 3 10-3. The pitch angle is 0 and the roll angles are 30 and 60 in Zheng et al. [136]. Table 13 shows the mechanical properties of the liquids and the experimental condition s used in these experiments. The authors plotted Rs vs. ReP for values of ReP ranging from 2 to 300 (see Figure 43). They found the existence of a critical value of the Reynolds number (Rec) below which the splitting ratio Rs vanishes, meaning that all liquid goes to the lower daughter. They also observed that Rs increases with ReP while in contrast, an increase in the value of a lead to a decrease in Rs and an increase in Rec. In the following, we simulate with our numerical model precisely the same conditions used in these experiments. Figure 43 displays comparisons of the splitting factor measured experimentally (symbols) with ourtheoretical predictions (lines) for diferent values of ReP. Again, our simulation results have captured the trends of the experimental data. We observer here a critical Reynolds number and an increase in the Rs with an increase of ReP and decrease of .

Validation of the surfactant delivery model in the entire lung

In this section, we verify and validate our computer simulation models with two animal experiments surfactant delivery. The irst experiment explores the propagation of surfactant for various dose volumes and the second for multiple instillations.

Changing the dose volume: comparison with experimental results

To validate our model, we have compared it with experimental results obtained by Gary Nieman’s team (State University of New York Upstate Medical University) in rats when testing diferent dose volumes. All experiments were conducted with approval from the State University of New York Upstate Medical University Institutional Animal Care and Use Committee. For the experiments, three male Sprague-Dawley rats weighing ~450 g were anesthetized with 1 mL.kg-1 of Ketamine/Xylazine I.P. and surgically prepared with a tracheotomy. Rats were then mechanically ventilated with a 6 mL.kg-1 tidal volume (Vt), 2 positive end-expiratory pressure (PEEP), 21% inspiratory oxygen fractionation (FiO2), and a frequency of 20 breaths per minute (Dräger Medical, Evita Ininity V500) [103]. The animal was disconnected from the ventilator and positioned in left lateral decubitus and reverse Trendelenburg (L+R). One half of the surfactant/dye mixture was distributed by sliding a catheter into the endotracheal tube and forming a plug [102]. After 20 mechanical breaths, the animal was put in right lateral decubitus and reverse Trendelenburg and the procedure repeated. The lung was then clamped at inspiration, and the lungs were excised and immersed in 10% formalin for histological examination. Infasurf® surfactant (210 mg) was tagged with Green Tissue Marking Dye® (Green Dye: WAK-Chemie Medical GmbH, Germany) at a concentration of 1% of the total volume of surfactant [146]. Three dose volumes per kg of surfactant 1.125, 2.5, and 5.8 mL.kg-1 were tested for experiments. The dye and surfactant mixture was incubated at 37°C until the time of distribution. Figure 44 shows the results for these diferent three-dose volumes per kg into the rat lung. There is a marked visual diference in surfactant distribution between the three-dose volumes per kg (Figure 44A-C). The low dose volume per kg (1.125 mL.kg-1) exhibits a scattered heterogeneous distribution in both right and left lungs. Increasing the instilled dose volume per kg to 2.5 mL.kg-1 resulted in a higher concentration of surfactant in the caudal portions of both lungs. For the highest instilled dose volume per kg (5.8 mL.kg-1), an even distribution of surfactant in the caudal portion of both lungs was observed while the remaining lung showed no surface distribution at all. In summary, the low dose volume per kg resulted in small areas of heterogeneous surfactant distribution whereas the high dose volume per kg induced a more locally homogeneous distribution isolated to the caudal portion of both lungs, indicating regional-scale heterogeneity. Of course, the heterogeneity observed here lies at the outer surface of the pulmonary airway system, which corresponds to the most distal part of the external acini. It is reasonable to assume that having surfactant reaching this surface implies that the corresponding acini are also illed with surfactant and this heterogeneity relects the 3D patchy distribution of surfactant in the lung volume. Our simulations (Figure 44D-F) support this assumption.
We have then carried out numerical simulations using our model in the same conditions. Figure 45A, B, and C present 3D views of the end distributions of surfactant in a rat lung after a double instillation in L+R posture, with instilled dose volumes per kg = 1.125 mL.kg-1, 2.5 mL.kg-1, and 5.8 mL.kg-1, respectively. The surfactant viscosity is =30 cP, and the low rate per kg is 6 mL.kg-1.s-1. This corresponds to the experiments presented in Figure 44, with 20 breathes per minute, a tidal volume per kg of 6 mL.kg-1, and a ratio between inspiration and exhalation times I:E=1:2. One observes that increasing the instilled dose volume allows more surfactant to reach the terminal regions. Indeed, the eiciency is raised from 5.9% to 45.6% and 76%, respectively, while the homogeneity index remains very poor, about 0.2 to 0.29. The amount of surfactant left coating the airways is displayed for all dose volumes per kg in Figure 45D, E, and F. In the two last cases, the coating cost VC is about 0.45 mL, only 30% more than the one found for a 1.125 mL.kg-1 instilled dose volume per kg, whereas the amount of instilled dose volume per kg is 2 and 5 times larger, respectively. VC reaches a plateau above a given initial dose volume per kg. As we can see, the end distributions of surfactant in rat lungs are very poor, both in our simulations and in the experiments. However, apart from the clinical result, the results of our simulations have the same trend as experiments.

READ  enzymatic characterization and cellular localization of a novel protein methyltransferase in sporozoite, liver and erythrocytic stage parasite.

Mechanical properties of surfactant

As mentioned earlier, several clinical trials of SRT in adults have shown no signiicant improvement in the number of survival of ARDS/ALI [62][72][73][74][84][70][71]. The question then arises of the origin of this failure: might it be due to the type of surfactant that was used, to its phospholipid concentration, or is there some mechanical origin in which not only the dose volume per (mL.kg-1) but also the surfactant properties (density, viscosity, and surface tension) would play the primary role. To shed light on this issue, we have performed simulations of delivery for various types of surfactant.

Table of contents :

1 STATE OF THE ART 
1.1 THE GEOMETRY OF THE PULMONARY AIRWAY TREE
1.1.1 THE HUMAN LUNG
1.1.2 ANIMAL LUNG
1.1.2.1 Rat lung
1.1.2.2 Pig lung
1.2 LUNG DISEASES
1.2.1 ARDS AND NRDS
1.3 SURFACTANT REPLACEMENT THERAPY
1.4 SURFACTANT PROPERTIES
1.4.1 COMPOSITION OF PULMONARY SURFACTANT
1.4.2 MECHANICAL PROPERTIES OF SURFACTANT
1.4.2.1 Surface tension
1.4.2.2 Viscosity
1.5 SURFACTANT ADMINISTRATION DELIVERY
1.6 CONCLUSION
2 GEOMETRICAL MODELS OF THE TRACHEOBRONCHIAL TREE IN MAMMALS
2.1 GEOMETRICAL PARAMETERIZATION
2.1.1 MODEL OF THE RAT LUNG
2.1.2 MODEL OF THE PIG LUNG
2.1.3 MODEL OF THE HUMAN LUNG
2.1.3.1 Symmetric airways tree (Weibel’s model)
2.1.3.2 Weibel-based asymmetric airway tree
2.1.3.3 Raabe-based asymmetric airways tree
3 MATHEMATICAL & NUMERICAL MODEL OF SURFACTANT DELIVERY
3.1 MODELING OF PROPAGATION OF THE LIQUID PLUG INTO THE AIRWAY TREE 
3.1.1 THE COATING LAYER
3.1.2 THE SPLITTING RATIO
3.1.3 EQUATION ON RS
3.1.3.1 Dimensionless equation
3.1.3.2 The splitting factor
3.1.3.3 The symmetric bifurcation
3.2 MODELING OF MULTIPLE ALIQUOT INSTILLATIONS
3.3 ASSESSING THE PERFORMANCE OF SURFACTANT DELIVERY
3.4 SURFACTANT PROPERTIES AND INSTILLATION CONDITIONS
3.4.1 FLOW RATE
3.4.2 DOSE VOLUME AND SURFACTANT PROPERTIES
3.4.3 POSTURE 69
3.5 VALIDATION OF THE SPLITTING MODEL
3.5.1 EFFECT OF GRAVITY ON LIQUID PLUG SPLITTING AT A BIFURCATION
3.5.1.1 Changing 
3.5.1.2 Changing
3.5.1.3 Changing the Bond number
3.5.2 EFFECT OF INERTIA AND GRAVITY ON LIQUID PLUG SPLITTING AT A BIFURCATION
3.5.2.1 Changing 
3.6 VALIDATION OF THE SURFACTANT DELIVERY MODEL IN THE ENTIRE LUNG
3.6.1 CHANGING THE DOSE VOLUME: COMPARISON WITH EXPERIMENTAL RESULTS
3.6.2 MULTIPLE INSTILLATIONS: COMPARISON WITH EXPERIMENTAL RESULTS
4 SIMULATIONS OF SURFACTANT DELIVERY IN RAT, PIG, AND HUMAN PULMONARY AIRWAYS SYSTEMS 
4.1 A BRIEF HISTORY OF SRT
4.2 SURFACTANT DELIVERY IN THE RAT LUNG
4.2.1 SYMMETRIC VS. ASYMMETRIC LUNG MODEL
4.2.2 FLOW RATE AND DOSE VOLUME
4.2.3 ASSESSING THE ROLE OF POSTURE
4.2.4 MECHANICAL PROPERTIES OF SURFACTANT
4.2.4.1 Viscosity
4.2.4.2 Surface tension
4.2.5 INSTILLATION TECHNIQUE
4.2.6 CONCLUSION
4.3 SURFACTANT DELIVERY IN THE PIG LUNG
4.3.1 FLOW RATE AND DOSE VOLUME
4.3.2 ASSESSING THE ROLE OF POSTURE
4.3.3 MECHANICAL PROPERTIES OF SURFACTANT
4.3.3.1 Viscosity
4.3.3.2 Surface tension
4.3.4 INSTILLATION TECHNIQUE
4.3.5 CONCLUSION
4.4 SRT IN THE HUMAN LUNG
4.4.1 NEONATE VS. ADULT
4.4.1.1 Flow rate and dose volume
4.4.1.2 Assessing the role of posture
4.4.1.3 Changing the mechanical properties of surfactant
4.4.1.3.1 Viscosity
4.4.1.3.2 Surface tension
4.4.2 AGE STUDY
4.4.3 SYMMETRIC VS. ASYMMETRIC TREE
4.4.4 SRT IN THE WEIBEL-BASED ASYMMETRIC TREE
4.4.4.1 Assessing the role of posture
4.4.4.2 Mechanical properties of surfactant
4.4.4.2.1 Viscosity
4.4.4.2.2 Surface tension
4.4.4.3 Multiple-aliquot Instillation
4.4.5 WEIBEL-BASED VS. RAABE-BASED ASYMMETRIC TREES
4.4.6 CONCLUSION
5 DISCUSSION & CONCLUSION 
5.1 DISCUSSION
5.2 CONCLUSION & PERSPECTIVES
6 REFERENCES 
7 LIST OF FIGURES 
8 LIST OF TABLES

GET THE COMPLETE PROJECT

Related Posts