scholarly journals EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung

2019 ◽  
Vol 48 (2) ◽  
pp. 747-756 ◽  
Author(s):  
Sarah Klein ◽  
Felix Hesselmann ◽  
Suzana Djeljadini ◽  
Tanja Berger ◽  
Anja Lena Thiebes ◽  
...  

AbstractIn the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a non-thrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today’s oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n = 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future.

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sarah Menzel ◽  
Nicole Finocchiaro ◽  
Christine Donay ◽  
Anja Lena Thiebes ◽  
Felix Hesselmann ◽  
...  

In patients with respiratory failure, extracorporeal lung support can ensure the vital gas exchange via gas permeable membranes but its application is restricted by limited long-term stability and hemocompatibility of the gas permeable membranes, which are in contact with the blood. Endothelial cells lining these membranes promise physiological hemocompatibility and should enable prolonged application. However, the endothelial cells increase the diffusion barrier of the blood-gas interface and thus affect gas transfer. In this study, we evaluated how the endothelial cells affect the gas exchange to optimize performance while maintaining an integral cell layer. Human umbilical vein endothelial cells were seeded on gas permeable cell culture membranes and cultivated in a custom-made bioreactor. Oxygen transfer rates of blank and endothelialized membranes in endothelial culture medium were determined. Cell morphology was assessed by microscopy and immunohistochemistry. Both setups provided oxygenation of the test fluid featuring small standard deviations of the measurements. Throughout the measuring range, the endothelial cells seem to promote gas transfer to a certain extent exceeding the blank membranes gas transfer performance by up to 120%. Although the underlying principles hereof still need to be clarified, the results represent a significant step towards the development of a biohybrid lung.


2021 ◽  
Author(s):  
Tiago DG Nunes ◽  
Magdalena W Slawinska ◽  
Heike Lindner ◽  
Michael T Raissig

Stomata are cellular pores on the leaf epidermis that allow plants to regulate carbon assimilation and water loss. Stomata integrate environmental signals to regulate pore apertures and optimize gas exchange to fluctuating conditions. Here, we quantified intraspecific plasticity of stomatal gas exchange and anatomy in response to seasonal variation in Brachypodium distachyon. Over the course of two years we (i) used infrared gas analysis to assess light response kinetics of 120 Bd21-3 wild-type individuals in an environmentally fluctuating greenhouse and (ii) microscopically determined the seasonal variability of stomatal anatomy in a subset of these plants. We observed systemic environmental effects on gas exchange measurements and remarkable intraspecific plasticity of stomatal anatomical traits. To reliably link anatomical variation to gas exchange, we adjusted anatomical gsmax calculations for grass stomatal morphology. We propose that systemic effects and variability in stomatal anatomy should be accounted for in long-term gas exchange studies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Silvia Coppola ◽  
Tommaso Pozzi ◽  
Martina Gurgitano ◽  
Alessandro Liguori ◽  
Ejona Duka ◽  
...  

Abstract Background The ARDS is characterized by different degrees of impairment in oxygenation and distribution of the lung disease. Two radiological patterns have been described: a focal and a diffuse one. These two patterns could present significant differences both in gas exchange and in the response to a recruitment maneuver. At the present time, it is not known if the focal and the diffuse pattern could be characterized by a difference in the lung and chest wall mechanical characteristics. Our aims were to investigate, at two levels of PEEP, if focal vs. diffuse ARDS patterns could be characterized by different lung CT characteristics, partitioned respiratory mechanics and lung recruitability. Methods CT patterns were analyzed by two radiologists and were classified as focal or diffuse. The changes from 5 to 15 cmH2O in blood gas analysis and partitioned respiratory mechanics were analyzed. Lung CT scan was performed at 5 and 45 cmH2O of PEEP to evaluate lung recruitability. Results One-hundred and ten patients showed a diffuse pattern, while 58 showed a focal pattern. At 5 cmH2O of PEEP, the driving pressure and the elastance, both the respiratory system and of the lung, were significantly higher in the diffuse pattern compared to the focal (14 [11–16] vs 11 [9–15 cmH2O; 28 [23–34] vs 21 [17–27] cmH2O/L; 22 [17–28] vs 14 [12–19] cmH2O/L). By increasing PEEP, the driving pressure and the respiratory system elastance significantly decreased in diffuse pattern, while they increased or did not change in the focal pattern (Δ15-5: − 1 [− 2 to 1] vs 0 [− 1 to 2]; − 1 [− 4 to 2] vs 1 [− 2 to 5]). At 5 cmH2O of PEEP, the diffuse pattern had a lower lung gas (743 [537–984] vs 1222 [918–1974] mL) and higher lung weight (1618 [1388–2001] vs 1222 [1059–1394] g) compared to focal pattern. The lung recruitability was significantly higher in diffuse compared to focal pattern 21% [13–29] vs 11% [6–16]. Considering the median of lung recruitability of the whole population (16.1%), the recruiters were 65% and 22% in the diffuse and focal pattern, respectively. Conclusions An early identification of lung morphology can be useful to choose the ventilatory setting. A diffuse pattern has a better response to the increase of PEEP and to the recruitment maneuver.


2007 ◽  
Vol 26 (2) ◽  
pp. 133-134 ◽  
Author(s):  
Roderick Thomas Mitchell ◽  
Richard Thompson ◽  
Sumesh Thomas

UMBILICAL ARTERY catheters (UACs) are commonly used in neonates and particularly in premature babies. They are crucial in enabling accurate blood pressure monitoring, blood gas analysis, and blood sampling. There is a relatively low rate of major complications with these catheters; however, complications may result from fracture or transection of the catheter.1,2Complications of retained UACs include hemorrhage and thromboembolic events. Long-term sequelae have also been described, including limb abnormalities as a result of ischemia and recurrent umbilical infection following unrecognized retained UACs.2,3We report a case of accidental transection of a UAC and subsequent migration of the catheter into the arterial circulation. This resulted in the premature baby requiring a laparotomy to retrieve the catheter. We describe the events leading to the transection, present its operative management, and offer suggestions for preventing this complication.


2021 ◽  
Vol 23 (1) ◽  
pp. 211
Author(s):  
Mikhail V. Samsonov ◽  
Nikita V. Podkuychenko ◽  
Asker Y. Khapchaev ◽  
Eugene E. Efremov ◽  
Elena V. Yanushevskaya ◽  
...  

Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.


1985 ◽  
Vol 58 (2) ◽  
pp. 506-513
Author(s):  
H. I. Modell ◽  
P. Beeman ◽  
J. Mendenhall

Available data relating duration of +GZ stress to blood gas exchange status is limited. Furthermore, studies focusing on pulmonary gas exchange during +GZ stress when abdominal restriction is imposed have yielded conflicting results. To examine the time course of blood gas changes occurring during exposure to +GZ stress in dogs and the influence of G-suit abdominal bladder inflation on this time course, seven spontaneously breathing pentobarbital-anesthetized adult mongrel dogs were exposed to 60 s of up to +5 GZ stress with and without G-suit abdominal bladder inflation. Arterial and mixed venous blood were sampled for blood gas analysis during the first and last 20 s of the exposure and at 3 min postexposure. Little change in blood gas status was seen at +3 GZ regardless of G-suit status. However, with G-suit inflation, arterial PO2 fell by a mean of 14.7 Torr during the first 20 s at +4 Gz (P less than 0.01, t test) and 20.6 Torr at +5 GZ (P less than 0.01). It continued to fall an additional 10 Torr during the next 40 s at both +4 and +5 GZ. Arterial PO2 was still 5–10 Torr below control values (P less than 0.05) 3 min postexposure. A second series of experiments paralleling the first focused on blood gas status during repeated exposure to acceleration. Blood gas status was assessed in five dogs during the late 20 s of two 60-s exposures separated by 3 min at 0 GZ. No significant differences between the initial and repeated exposures were detected. The data indicate that G-suit abdominal bladder inflation promotes increased venous admixture.


1987 ◽  
Author(s):  
M P Wautier ◽  
J L Wautier

The culture of human endothelial cells is largely used for vascular research. The possibility of developping long term culture of human endothelial cells (EC) raised the question regarding the identity after several passages. To further investigate this aspect we have cultured human umbilical vein EC until the 12th passage on fibronectin coated dishes supplemented with ECGF. We have studied the EC morphology by light and electron microscopy, the reactivity with 51Cr labelled platelets, and prostacyclin synthesis. Until the 6th passage no major change could be noted, except the occurence of rare large EC and a reduction in the doubling time between 2nd and 5th passage. After the 7th passage up to the 10th EC became more elongated and did not grow in strict monolayer. The number of vacuoles and mitochondria increased as well as the doubling time. After the 12th passage the EC were still viable but proliferated very slowly. The adhesion of radiolabelled platelets dramatically increased (150%) and PGI2 production significantly decreased (6 Keto PGF1α : 1st passage 13±2.5 ng; 6th passage 0.33±0.27 ng/106 EC). In our culture conditions EC kept most of their original characteristics up to the 6th passage but then lost some of them. At any passage EC contained Weibel Palade bodies and von Willebrand factor. We can conclude that after the 7th passage EC in culture are different from the original cells and could possibly represent an in vitro model of EC ageing.


PEDIATRICS ◽  
1976 ◽  
Vol 57 (5) ◽  
pp. 681-690
Author(s):  
R. Huch ◽  
A. Huch ◽  
M. Albani ◽  
M. Gabriel ◽  
F. J. Schulte ◽  
...  

Results are reported concerning the clinical application of the transcutaneous Po2 method (tc Po2 method) according to Huch et al. for monitoring arterial Po2. Thirty long-term continuous tc Po2 recordings were made in 22 ventilated children and infants with cardiorespiratory problems in four different pediatric intensive care units (Zürich, Göttingen, Kassel, and Mainz). These recordings were compared with 132 arterial Po2 determinations made during the same period of time. There was a linear relationship and a close correspondence between arterial Po2 and tc Po2 (r = .94). The continuous recordings have shown that the variability of Po2 is much greater than assumed so far by single blood gas analysis. This fact restricts greatly the value of single samples. Continuous tc Po2 monitoring has proved to be a great help in optimal respirator setting.


2003 ◽  
Vol 285 (4) ◽  
pp. C813-C822 ◽  
Author(s):  
Nilesh M. Dagia ◽  
Douglas J. Goetz

A promising approach for reducing aberrant leukocyte-endothelial adhesion during pathological inflammation is to inhibit endothelial cell adhesion molecule (ECAM) expression at the transcription level. Several compounds have been shown to decrease cytokine-induced upregulation of ECAMs primarily by modulating the activity of transcription factors [e.g., nuclear factor-κB (NF-κB)]. The majority of the in vitro studies have focused on the effect of transcription inhibitors on endothelial cells exposed to a single cytokine [primarily tumor necrosis factor-α (TNF-α)] for a relatively short period of time (primarily 4-6 h). However, in the in vivo setting, multiple cytokines [e.g., interleukin-1β (IL-1β) and TNF-α] may be present for extended periods of time. Thus we studied the effects of a transcription inhibitor, the proteasome inhibitor lactacystin, on ECAM expression and myeloid (HL60) cell adhesion to human umbilical vein endothelial cells (HUVEC) activated by concurrent, sequential, and long-term (24 h) treatment with IL-1β and TNF-α. We show, for the first time, that lactacystin inhibits 1) 4-h concurrent IL-1β- and TNF-α-induced expression of E-selectin, VCAM-1, ICAM-1, and HL60 cell adhesion to HUVEC; 2) 4-h TNF-α-induced expression of E-selectin, VCAM-1, and HL60 cell adhesion to HUVEC that have become desensitized to IL-1β activation; 3) 24-h TNF-α-induced expression of E-selectin and VCAM-1 but not ICAM-1; and 4) 24-h TNF-α-induced HL60 cell adhesion to HUVEC. Combined, our results demonstrate that a proteasome inhibitor can reduce concurrent, sequential, and long-term IL-1β- and TNF-α-induced ECAM expression and myeloid cell adhesion.


2003 ◽  
Vol 12 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Thomas P. Johnston ◽  
Yuai Li ◽  
Ahmed S. Jamal ◽  
Daniel J. Stechschulte ◽  
Kottarappat N. Dileepan

Coronary heart disease secondary to atherosclerosis is still the leading cause of death in the US. Animal models used for elucidating the pathogenesis of this disease primarily involve rabbits and pigs. Previous studies from this laboratory have demonstrated intraperitoneal injections of poloxamer 407 (P-407) in both male and female mice will lead to hyperlipidemia and atherosclerosis, suggesting the use of this polymer to develop a mouse model of atherosclerosis. In order to understand the mechanism of P-407-induced hyperlipidemia and vascular lesion formation, we evaluated the direct effects of P-407 on endothelial cell and macrophage functionsin vitro, and itsin vivoeffects on the oxidation of circulating lipids following long-term (4 month) administration. Our results demonstrated that incubation of P-407 with human umbilical vein endothelial cells in culture did not influence either cell proliferation or interleukin-6 and interleukin-8 production over a concentration range of 0-40 μM. In addition, nitric oxide production by macrophages was not affected by P-407 over a concentration range of 0-20 μM. Finally, we demonstrated that while P-407 could not induce the oxidation of LDL-Cin vitro, long-term (4 month) administration of P-407 in mice resulted in elevated levels of oxidized lipids in the plasma. Thus, it is suggested that the formation of atherosclerotic lesions in this mouse model of atherosclerosis does not result from either direct stimulation of endothelial cells or macrophage activation by P-407. Instead, these data would support the premise that oxidation of lipids (perhaps low-density lipoprotein cholesterol) by an indirect mechanism following injection of P-407 may represent one of the mechanisms responsible for atheroma formation.


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