Abstract
Background
A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The ...endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD).
Methods
After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema).
Results
Our results showed a significant improvement in gas exchange elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03) in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin–eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control.
Conclusions
These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Halbach cylinders have found various applications for their ability to produce strong and homogenous magnetostatic fields. Contrary to their conventional manual fabrication, we introduce a novel ...approach to automatically align multiple permanent magnets into a Halbach cylinder. The approach uses the magnetic field distribution from a diametrically magnetized cylindrical magnet to simultaneously align multiple magnets. The extent to which the automatic assembly can approximate a Halbach cylinder was analyzed using 3D Finite Element Modeling. Prototypes were built that demonstrated automatic alignment of eight magnets into Halbach cylinders. Automatic alignment eliminates the complexity of manually aligning Halbach cylinders.
•A new method for fabricating cylindrical Halbach array.•Simultaneously alignment of multiple magnets into Halbach cylinders.•Automatic alignment eliminates the complexity of manually aligning Halbach cylinders.
Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect ...both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-h ovine model of BSD.
Twelve healthy female sheep (37–42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 h. Plasma and BAL endothelin-1 and cytokines (IL-1β, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma.
Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 h post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1 × 109 cells/L 95% confidence interval (CI) 2.06–4.14 vs. 6 × 109 cells/L 95%CI 3.92–7.97; p < 0.01) and BAL (4.5 × 109 cells/L 95%CI 0.41–9.41 vs. 26 95%CI 12.29–39.80; p = 0.03) after 6 h of BSD induction vs baseline. A significant increase in ANP production (20.28 pM 95%CI 16.18–24.37 vs. 78.68 pM 95%CI 53.16–104.21; p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 95%CI 2.69–5.83 ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 h.
BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.
Thin and flexible polymeric membranes play a critical role in tissue engineering applications for example organs-on-a-chip. These flexible membranes can enable mechanical stretch of the engineered ...tissue to mimic organ-specific biophysical features, such as breathing. In this work, we report the fabrication of thin (<20 μm), stretchable, and biocompatible polyurethane (PU) membranes. The membranes were fabricated using spin coating technique on silicon substrates and were mounted on a frame for ease of device integration and handling. The membranes were characterized for their optical and elastic properties and compatibility with cell/tissue culture. It was possible to apply up to 10 kilopascal (kPa) pressure to perform cyclic stretch on 4 mm-diameter membranes for a period of 2 weeks at 0.2 hertz (Hz) frequency without mechanical failure. Adenocarcinomic human alveolar basal epithelial (A549) cells were cultured on the apical side of the PU membrane. The morphology and viability of the cells were comparable to those of cells cultured on standard tissue culture plates. Our experiments suggest that the stretchable PU membrane will be broadly useful for various tissue engineering applications
in vitro
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