Open Access
Salbutamol transport and deposition in healthy cat airways under different breathing conditions and particle sizes
(Frontiers Media, 2023) Fernández-Parra, Rocío; Pey, Pascaline; Reinero, Carol; Malvè, Mauro; Ingeniería; Ingeniaritza
Salbutamol is a bronchodilatator commonly used for the treatment of feline inflammatory lower airway disease, including asthma or acute bronchospasm. As in humans, a pressurized metered dose inhaler (pMDI) is used in conjunction with a spacer and a spherical mask to facilitate salbutamol administration. However, efficacy of inhalation therapy is influenced by different factors including the noncooperative character of cats. In this study, the goal was to use computational fluid dynamics (CFD) to analyze the impact of breathing patterns and salbutamol particle size on overall drug transport and deposition using a specific spherical mask and spacer designed for cats. A model incorporating three-dimensional cat airway geometry, a commercially available spherical mask, and a 10 cm spacer, was used for CFD analysis. Two peak inspiratory flows were tested: 30 mL/s and 126 mL/s. Simulations were performed with 30s breathing different inspiratory and expiratory times, respiratory frequencies and peaks. Droplet spray transport and deposition were simulated with different particle sizes typical of the drug delivery therapies (1, 5, 10, and 15 μm). The percentage of particle deposition into the device and upper airways decreased with increasing particle diameter during both flows imposed in this cat model. During increased mean ventilatory rate (MVR) conditions, most of the salbutamol was lost in the upper airways. And during decreased MVR conditions, most of the particles remained in suspension (still in hold-up) between the mask and the carina, indicating the need for more than 30 s to be transported. In both flows the percentage of particles traveling to the lung was low at 1.5%–2.3%. In conclusion, in contrast to what has been described in the human literature, the results from this feline model suggest that the percentage of particles deposited on the upper airway decreases with increasing particle diameter.
Open Access
Impact of geometric and hemodynamic changes on a mechanobiological model of atherosclerosis
(Elsevier, 2024) Hernández-López, Patricia; Cilla, Myriam; Martínez, Miguel Ángel; Peña, Estefanía; Malvè, Mauro; Ingeniería; Ingeniaritza
Background and objective: in this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. Methods: for that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection¿diffusion¿reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material. Results: significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. Conclusions: the findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.
Open Access
An image-based framework for the analysis of the murine microvasculature: from tissue clarification to computational hemodynamics
(MDPI, 2022) Mañosas Sánchez, Santiago; Sanz Muñoz, Aritz; Ederra, Cristina; Urbiola, Ainhoa; Rojas De Miguel, Elvira; Ostiz, Ainhoa; Cortés Domínguez, Iván; Ramírez, Natalia; Ortiz de Solórzano, Carlos; Villanueva Larre, Arantxa; Malvè, Mauro; Ingeniería; Ingeniaritza
The blood–brain barrier is a unique physiological structure acting as a filter for every molecule reaching the brain through the blood. For this reason, an effective pharmacologic treatment supplied to a patient by systemic circulation should first be capable of crossing the barrier. Standard cell cultures (or those based on microfluidic devices) and animal models have been used to study the human blood–brain barrier. Unfortunately, these tools have not yet reached a state of maturity because of the complexity of this physiological process aggravated by a high heterogeneity that is not easily recapitulated experimentally. In fact, the extensive research that has been performed and the preclinical trials carried out provided sometimes contradictory results, and the functionality of the barrier function is still not fully understood. In this study, we have combined tissue clarification, advanced microscopy and image analysis to develop a one-dimensional computational model of the microvasculature hemodynamics inside the mouse brain. This model can provide information about the flow regime, the pressure field and the wall shear stress among other fluid dynamics variables inside the barrier. Although it is a simplified model of the cerebral microvasculature, it allows a first insight on into the blood–brain barrier hemodynamics and offers several additional possibilities to systematically study the barrier microcirculatory processes.
Open Access
Computational analysis of polymeric biodegradable and customizable airway stent designs
(MDPI, 2024-06-14) Ayechu Abendaño, Ada; Pérez-Jiménez, Aurora; Sánchez-Matás, Carmen; López-Villalobos, José Luis; Díaz Jiménez, Cristina; Fernández-Parra, Rocío; Malvè, Mauro; Ingeniería; Ingeniaritza
The placement of endotracheal prostheses is a procedure used to treat tracheal lesions when no other surgical options are available. Unfortunately, this technique remains controversial. Both silicon and metallic stents are used with unpredictable success rates, as they have advantages but also disadvantages. Typical side effects include restenosis due to epithelial hyperplasia, obstruction and granuloma formation. Repeat interventions are often required. Biodegradable stents are promising in the field of cardiovascular biomechanics but are not yet approved for use in the respiratory system. The aim of the present study is to summarize important information and to evaluate the role of different geometrical features for the fabrication of a new tracheo-bronchial prosthesis prototype, which should be biodegradable, adaptable to the patient’s lesion and producible by 3D printing. A parametric design and subsequent computational analysis using the finite element method is carried out. Two different stent designs are parameterized and analyzed. The biodegradable material chosen for simulations is polylactic acid. Experimental tests are conducted for assessing its mechanical properties. The role of the key design parameters on the radial force of the biodegradable prosthesis is investigated. The computational results allow us to elucidate the role of the pitch angle, the wire thickness and the number of cells or units, among other parameters, on the radial force. This work may be useful for the design of ad hoc airway stents according to the patient and type of lesion.
Open Access
A theoretical model of the endothelial cell morphology due to different waveforms
(Elsevier, 2015) Sáez, Pablo; Malvè, Mauro; Martínez, Miguel Ángel; Ingeniería Mecánica, Energética y de Materiales; Mekanika, Energetika eta Materialen Ingeniaritza
Endothelial cells are key units in the regulatory biological process of blood vessels. They represent an interface to transmit variations on the fluid dynamic changes. They are able to adapt its cytoskeleton, by means of microtubules reorientation and F-actin reorganization, due to new mechanical environments. Moreover, they are responsible for initiating a huge cascade of biological processes, such as the release of endothelins (ET-1), in charge of the constriction of the vessel and growth factors such as TGF β and PDGF. Although a huge efforts have been made in the experimental characterization and description of these two issues the computational modeling has not gained such an attention. In this work we study the 3D remodeling of endothelial cells based on the main features of blood flow. In particular we study how different oscillatory shear index and the time average wall shear stresses modify the endothelial cell shape. We found our model fitted the experimental works presented before in in vitro studies. We also include our model within a computational fluid dynamics simulation of a carotid artery to evaluate endothelial cell shape index which is a key predictor of atheroma plaque formation. Moreover, our approach can be coupled with models of collagen and smooth muscle cell growth, where remodeling and the associated release of chemical substance are involved.
Open Access
Nasal anatomy and sniffing in respiration and olfaction of wild and domestic animals
(Frontiers Media, 2023) Xi, Jinxiang; Si, Xiuhua April; Malvè, Mauro; Ingeniería; Ingeniaritza
Animals have been widely utilized as surrogate models for humans in exposure testing, infectious disease experiments, and immunology studies. However, respiratory diseases affect both humans and animals. These disorders can spontaneously affect wild and domestic animals, impacting their quality and quantity of life. The origin of such responses can primarily be traced back to the pathogens deposited in the respiratory tract. There is a lack of understanding of the transport and deposition of respirable particulate matter (bio-aerosols or viruses) in either wild or domestic animals. Moreover, local dosimetry is more relevant than the total or regionally averaged doses in assessing exposure risks or therapeutic outcomes. An accurate prediction of the total and local dosimetry is the crucial first step to quantifying the dose-response relationship, which in turn necessitates detailed knowledge of animals' respiratory tract and flow/aerosol dynamics within it. In this review, we examined the nasal anatomy and physiology (i.e., structure-function relationship) of different animals, including the dog, rat, rabbit, deer, rhombus monkey, cat, and other domestic and wild animals. Special attention was paid to the similarities and differences in the vestibular, respiratory, and olfactory regions among different species. The ventilation airflow and behaviors of inhaled aerosols were described as pertinent to the animals' mechanisms for ventilation modulation and olfaction enhancement. In particular, sniffing, a breathing maneuver that animals often practice enhancing olfaction, was examined in detail in different animals. Animal models used in COVID-19 research were discussed. The advances and challenges of using numerical modeling in place of animal studies were discussed. The application of this technique in animals is relevant for bidirectional improvements in animal and human health.
Open Access
Modelling particle transport and deposition in the human healthy and stented tracheobronchial airways
(Springer, 2020) Malvè, Mauro; Sánchez-Matás, Carmen; López-Villalobos, José Luis; Ingeniería; Ingeniaritza
The main goal of this study is the quantification of the particle transport and deposition within the human airways during light, normal and exercise breathing conditions using the computational fluid dynamics. In particular we presented a comparison between healthy and stented airways. The considered tracheobronchial model is based on the Weibel symmetric model in which we have inserted the Dumon prosthesis at different locations and on the CT- based geometries of a healthy and a stented airway. The results indicate an important redistribution of the particle deposition locations. Local overdoses can be found in the proximal regions of the prostheses, independently of the breathing conditions, of the particle size and of the considered geometry. The presented work is aimed to contribute to the understanding of the particle deposition in the human lung and to improve drug-aerosol therapies. For patients that underwent airways reconstructive surgery, it can give detailed information about the deposition efficiency and it may help targeting specific airways regions.
Open Access
On studying the interaction between different stent models and rabbit tracheal tissue: numerical, endoscopic and histological comparison
(Biomedical Engineering Society, 2016) Chaure, J.; Serrano, C.; Fernández-Parra, Rocío; Peña, Estefanía; Malvè, Mauro; Ingeniería Mecánica, Energética y de Materiales; Mekanika, Energetika eta Materialen Ingeniaritza
Stenting technique is employed worldwide for treating atherosclerotic vessel and tracheal stenosis. Both diseases can be treated by means of metallic stents which present advantages but are affected by the main problem of restenosis of the stented area. In this study we have built a rabbit trachea numerical model and we have analyzed it before and after insertion and opening of two types of commercial stent: a Zilver® FlexTM Stent and a WallStentTM. In experimental parallel work, two types of stent were implanted in 30 New Zealand rabbits divided in two groups of 10 animals corresponding to each stent type and a third group made up of 10 animals without stent. The tracheal wall response was assessed by means of computerized tomography by endoscopy, macroscopic findings and histopathological study 90 days after stent deployment. Three idealized trachea models, one model for each group, were created in order to perform the computational study. The animal model was used to validate the numerical findings and to attempt to find qualitative correlations between numerical and experimental results. Experimental findings such as inflammation, granuloma and abnormal tissue growth, assessed from histomorphometric analyses were compared with derived numerical parameters such as wall shear stress (WSS) and maximum principal stress. The direct comparison of these parameters and the biological response supports the hypothesis that WSS and tensile stresses may lead to a greater tracheal epithelium response within the stented region, with the latter seeming to have the dominant role. This study may be helpful for improving stent design and demonstrates the feasibility offered by in-silico investigated tracheal structural and fluid dynamics.
Open Access
Experimental bench for hemodynamic study of coronary artery with serial stenoses: fractional flow reserve assessment
(Taylor & Francis, 2017) Coppel, R.; Gómez, A. L.; Finet, G.; Malvè, Mauro; Pettigrew, R. I.; Ingeniería Mecánica, Energética y de Materiales; Mekanika, Energetika eta Materialen Ingeniaritza
The aim of this study was to develop an experimental hemodynamic bench to elucidate the influences of such geometrical parameters on the FFR assessment. As a first approach, the present work was focused on the influence of the severity of S1 and S2.
Open Access
Computational fluid dynamics comparison of the upper airway velocity, pressure, and resistance in cats using an endotracheal tube or a supraglottic airway device
(Frontiers Media, 2023) Zamora -Perarnau, Carla; Malvè, Mauro; Fernández-Parra, Rocío; Ingeniería; Ingeniaritza
Intoduction: In veterinary medicine, airway management of cats under general anesthesia is performed with an endotracheal tube (ETT) or supraglottic airway device (SGAD). This study aims to describe the use of computational fluid dynamics (CFD) to assess the velocities, pressures, and resistances of cats with ETT or SGAD. Methods: A geometrical reconstruction model of the device, trachea, and lobar bronchi was carried out from computed tomography (CT) scans that include the head, neck, and thorax. Twenty CT scans of cats under general anesthesia using ETT (n = 10) and SGAD (n = 10) were modeled and analyzed. An inspiratory flow of 2.4 L/min was imposed in each model and velocity (m/s), general and regional pressures (cmH2O) were computed. General resistance (cmH2O/L/min) was calculated using differential pressure differences between the device inlet and lobar bronchi. Additionally, regional resistances were calculated at the device¿s connection with the breathing circuit (region A), at the glottis area for the SGAD, and the area of the ETT exit (bevel) (region B) and the device itself (region C). Results: Recirculatory flow and high velocities were found at the ETT¿s bevel and at the glottis level in the SGAD group. The pressure gradient (¿p) was more enhanced in the ETT cases compared with the SGAD cases, where the pressure change was drastic. In region A, the ¿p was higher in the ETT group, while in regions B and C, it was higher in the SGAD group. The general resistance was not statistically significant between groups (p = 0.48). Higher resistances were found at the region A (p = <0.001) in the ETT group. In contrast, the resistance was higher in the SGAD cases at the region B (p = 0.001). Discussion: Overall, the provided CT-based CFD analysis demonstrated regional changes in airway pressure and resistance between ETT and SGAD during anesthetic flow conditions. Correct selection of the airway device size is recommended to avoid upper airway obstruction or changes in flow parameters.