Microvascular fluid flow in ex vivo and engineered lungs

Author(s):  
Micha Sam Brickman Raredon ◽  
Alexander James Engler ◽  
Yifan Yuan ◽  
Allison Marie Greaney ◽  
Laura E. Niklason

In recent years, it has become common to experiment with ex vivo perfused lungs for organ transplantation, and to attempt regenerative pulmonary engineering using decellularized lung matrices. However, our understanding of the physiology of ex vivo organ perfusion is imperfect: it is not currently well understood how decreasing microvascular barrier affects the perfusion of pulmonary parenchyma. Additionally, protocols for lung perfusion and organ culture fluid-handling are far from standardized, with widespread variation on both basic methods and on ideally controlled parameters. To address both of these deficits, a robust, non-invasive, and mechanistic model is needed which is able to predict microvascular resistance and permeability in perfused lungs while providing insight into capillary recruitment. Although validated mathematical models exist for fluid flow in native pulmonary tissue, previous models generally assume minimal intravascular leak from artery to vein and do not assess capillary bed recruitment. Such models are difficult to apply to both ex vivo lung perfusions, in which edema can develop over time and microvessels can become blocked, and to decellularized ex vivo organomimetic cultures, in which microvascular recruitment is variable and arterially-perfused fluid enters into the alveolar space. Here, we develop a mathematical model of pulmonary microvascular fluid flow which is applicable in both instances, and we apply our model to data from native, decellularized, and regenerating lungs under ex vivo perfusion. The results provide substantial insight into microvascular pressure-flow mechanics, while producing previously unknown output values for tissue-specific capillary-alveolar hydraulic conductivity, microvascular recruitment, and total organ barrier resistance.

Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Agnieszka Michalak ◽  
Anna Pankowska ◽  
Paulina Kozioł ◽  
...  

AbstractMephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.


2014 ◽  
Vol 136 (11) ◽  
Author(s):  
Wilfried Bürzle ◽  
Edoardo Mazza ◽  
John J. Moore

Puncture testing has been applied in several studies for the mechanical characterization of human fetal membrane (FM) tissue, and significant knowledge has been gained from these investigations. When comparing results of mechanical testing (puncture, inflation, and uniaxial tension), we have observed discrepancies in the rupture sequence of FM tissue and significant differences in the deformation behavior. This study was undertaken to clarify these discrepancies. Puncture experiments on FM samples were performed to reproduce previous findings, and numerical simulations were carried out to rationalize particular aspects of membrane failure. The results demonstrate that both rupture sequence and resistance to deformation depend on the samples' fixation. Soft fixation leads to slippage in the clamping, which reduces mechanical loading of the amnion layer and results in chorion rupturing first. Conversely, the stiffer, stronger, and less extensible amnion layer fails first if tight fixation is used. The results provide a novel insight into the interpretation of ex vivo testing as well as in vivo membrane rupture.


Radiology ◽  
2021 ◽  
pp. 203967
Author(s):  
Wen-Juan Lv ◽  
Xin-Yan Zhao ◽  
Dou-Dou Hu ◽  
Xiao-Hong Xin ◽  
Li-Li Qin ◽  
...  

2005 ◽  
Vol 95 (12) ◽  
pp. 1453-1461 ◽  
Author(s):  
Gaël Thébaud ◽  
Nathalie Peyrard ◽  
Sylvie Dallot ◽  
Agnès Calonnec ◽  
Gérard Labonne

Mapping and analyzing the disease status of individual plants within a study area at successive dates can give insight into the processes involved in the spread of a disease. We propose a permutation method to analyze such spatiotemporal maps of binary data (healthy or diseased plants) in regularly spaced plantings. It requires little prior information on the causes of disease spread and handles missing plants and censored data. A Monte Carlo test is used to assess whether the location of newly diseased plants is independent of the location of previously diseased plants. The test takes account of the significant spatial structures at each date in order to separate nonrandomness caused by the structure at one date from nonrandomness caused by the dependence between newly diseased plants and previously diseased plants. If there is a nonrandom structure at both dates, independent patterns are simulated by randomly shifting the entire pattern observed at the second date. Otherwise, independent patterns are simulated by randomly reallocating the positions of one group of diseased plants. Simulated and observed patterns of disease are then compared through distance-based statistics. The performance of the method and its robustness are evaluated by its ability to accurately identify simulated independent and dependent bivariate point patterns. Additionally, two realworld spatiotemporal maps with contrasting disease progress illustrate how the tests can provide valuable clues about the processes of disease spread. This method can supplement biological investigations and be used as an exploratory step before developing a specific mechanistic model.


2020 ◽  
Vol 64 (1-2-3) ◽  
pp. 213-225
Author(s):  
Wulligundam Praveen ◽  
Saloni Sinha ◽  
Rajarshi Batabyal ◽  
Kajal Kamat ◽  
Maneesha S. Inamdar

Over the last two decades, an exponential growth in technologies and techniques available to biologists has provided mind-boggling quantities of data and led to information overload. Yet, answers to fundamental questions such as “how are we made?” and “what keeps us ticking?” remain incomplete. Developmental biology has provided elegant approaches to address such questions leading to enlightening insights. While several important contributions to developmental biology have come from India over the decades, this area of research remains nascent. Here, we review the journey in India, from the discovery of the ociad gene family to decoding its role in development and stem cells. We compare analysis in silico, in vivo and ex vivo, with developmental models such as Drosophila, mouse and stem cells that gave important insight into how these clinically significant genes function.


2016 ◽  
Vol 140 (3) ◽  
pp. 212-220 ◽  
Author(s):  
Erik Thunnissen ◽  
Hans J. L. G. Blaauwgeers ◽  
Erienne M. V. de Cuba ◽  
Ching Yong Yick ◽  
Douglas B. Flieder

Context Surgical and pathologic handling of lung physically affects lung tissue. This leads to artifacts that alter the morphologic appearance of pulmonary parenchyma. Objective —To describe and illustrate mechanisms of ex vivo artifacts that may lead to diagnostic pitfalls. Design In this study 4 mechanisms of ex vivo artifacts and corresponding diagnostic pitfalls are described and illustrated. Results —The 4 patterns of artifacts are: (1) surgical collapse, due to the removal of air and blood from pulmonary resections; (2) ex vivo contraction of bronchial and bronchiolar smooth muscle; (3) clamping edema of open lung biopsies; and (4) spreading of tissue fragments and individual cells through a knife surface. Morphologic pitfalls include diagnostic patterns of adenocarcinoma, asthma, constrictive bronchiolitis, and lymphedema. Conclusion Four patterns of pulmonary ex vivo artifacts are important to recognize in order to avoid morphologic misinterpretations.


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