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Development of an ex vivo lung perfusion system focusing on the preservation of fresh animal lungs for experiments and storage
Mesíková, Klaudia ; Forjan, Mathias (oponent) ; Paštěka, Richard (vedoucí práce)
A mechanical combined lung model is a type of model used in human breathing simulation. The biggest currency of the model is a high similarity with the human lungs. In order to work with the animal lungs for a longer time and so follow the principles of the 3Rs, a perfusion system is involved in the procedure. The perfusion system filled with a chosen perfusate solution is responsible to prolong the period in which the animal lungs are viable for experiments and storage in the ex-vivo environment. The development of the properly functioning perfusion system is based on the several components included in the process. Choosing the right solution for the perfusion of the inner environment of the lungs is one of the most important things that need to be taken into account. The roller pump is considered the drive motor of the system. Pressure and flow sensors are responsible for monitoring the process parameters that could describe the functionality and the ability to preserve the animal lungs in the ex-vivo environment. The validation of the developed system by using the fresh animal lungs is a part of the thesis as well as the checking procedure of the solution’s influence with the time of the storage. The perfusion system was successfully created and tested. The pressure and flow parameters gained during the measurement were compared while using the saline solution, the Ringer’s solution, and Histofix in the system. The compliance parameter of the lungs were been monitored during the perfusion as well as during the storage with the aim to determine the behaviour of the preserved lungs with the time and the impact of the chosen solution on it. Compliance initially decreased and then stabilized at a certain value throughout the storage period. For the perfusion with the saline and Ringer’s solution, it dropped by one-third. For Histofix preservation, the drop was by half of the initial compliance. The preservation time without the presence of the tissue necrosis was 120 hours using the Saline solution, 240 hours using the Ringer’s solution, and at least 268 hours using Histofix. The perfusion system could further be used in medical research and make a positive aspect in terms of less consumption of the animal organs for experimental purposes in various fields of the research. For future research, the improvement of the perfusion system and solution composition to ensure even longer preservation is welcomed.
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Modeling of Airflow Characteristics and Particle Deposition in Human Upper Respiratory Tract Using CFD Simulations
Pospíšil, Milan ; Forjan, Mathias (oponent) ; Paštěka, Richard (vedoucí práce)
The objectives are to analyze the mechanisms of airflow and particle transport in the extrathoracic airways. Understanding these features in greater detail not only helps in the treatment of diseases related to the respiratory tract but also aims to reduce the amount of animal testing. For the evaluation, computational fluid dynamic (CFD) simulations were utilized. ANSYS was used as a leading software to perform a simulation of different inspiratory flow rates. In this work, Large Eddy Simulations (LES) is engaged due to its real-world performance. The geometry of the upper airways is obtained from CT scans, to preserve the topological data of the upper airways. Furthermore, the deposition of inhaled particles of varying diameters 1-10 m was examined, helping us better understand the therapeutic effects of inhaled particles. Two types of inhalations simulations were carried out. First, inhalation through the nose, simulating the inhalation with a nebulizer with airflow rates of 15 l/min and 30 l/min. Second, through mouth simulating inhalation with a dry-powder inhaler with a flow rate of 90 l/min. Simulated results show that most of the particles deposit at the entrance of the nasal or oral cavity. When flow rates of 15 and 30 l/min were compared, it can be seen the higher initial velocity is, the particles of large diameter (6-10 m) are stuck in the nasal cavity and do not appear in the laryngeal region, whereas with low velocity the more particles of 6-10 m can be found in this region. The maximum number of particles leaving the trachea was observed with a flow rate of 15 l/min, accounting for 26 %. As opposed to 90 l/min where only 13 % left the upper respiratory tract. Also, typical pressure drop can be observed in pressure contours describing the larynx region. This was most significant for a flow rate of 90 l/min where the pressure from the oropharynx to subglottis dropped by 490 Pa.
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Development of an ex vivo lung perfusion system focusing on the preservation of fresh animal lungs for experiments and storage
Mesíková, Klaudia ; Forjan, Mathias (oponent) ; Paštěka, Richard (vedoucí práce)
A mechanical combined lung model is a type of model used in human breathing simulation. The biggest currency of the model is a high similarity with the human lungs. In order to work with the animal lungs for a longer time and so follow the principles of the 3Rs, a perfusion system is involved in the procedure. The perfusion system filled with a chosen perfusate solution is responsible to prolong the period in which the animal lungs are viable for experiments and storage in the ex-vivo environment. The development of the properly functioning perfusion system is based on the several components included in the process. Choosing the right solution for the perfusion of the inner environment of the lungs is one of the most important things that need to be taken into account. The roller pump is considered the drive motor of the system. Pressure and flow sensors are responsible for monitoring the process parameters that could describe the functionality and the ability to preserve the animal lungs in the ex-vivo environment. The validation of the developed system by using the fresh animal lungs is a part of the thesis as well as the checking procedure of the solution’s influence with the time of the storage. The perfusion system was successfully created and tested. The pressure and flow parameters gained during the measurement were compared while using the saline solution, the Ringer’s solution, and Histofix in the system. The compliance parameter of the lungs were been monitored during the perfusion as well as during the storage with the aim to determine the behaviour of the preserved lungs with the time and the impact of the chosen solution on it. Compliance initially decreased and then stabilized at a certain value throughout the storage period. For the perfusion with the saline and Ringer’s solution, it dropped by one-third. For Histofix preservation, the drop was by half of the initial compliance. The preservation time without the presence of the tissue necrosis was 120 hours using the Saline solution, 240 hours using the Ringer’s solution, and at least 268 hours using Histofix. The perfusion system could further be used in medical research and make a positive aspect in terms of less consumption of the animal organs for experimental purposes in various fields of the research. For future research, the improvement of the perfusion system and solution composition to ensure even longer preservation is welcomed.
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