scholarly journals P-L14 Ex-vivo normothermic perfusion of an abattoir-derived porcine hepatic segment as a model for scientific research

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Trisha Kanani ◽  
Kareem ElSamani ◽  
Wen Chung ◽  
Michael Cox ◽  
Mohamed Sahloul ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Ex Vivo ◽  
Autologous Blood ◽  
Venous Pressure ◽  
Blood Gases ◽  
Bacterial Disease ◽  
Ex Vivo Model ◽  
Human Liver Tissue ◽  
Glucose Levels

Abstract Background The human immune response to bacterial and viral pathogens has been the focus of intense research, but details on the earliest phases of infection remain unclear. Better knowledge regarding the response of immune cells in the liver is important for the treatment of severe bacterial disease. Ex vivo perfusion which mimics physiological conditions of the liver may provide useful models for this research.  An ex vivo model which perfuses hepatic segments would allow translational research on a physiological and reliable model in the scarce resource of human organs. Here we describe the extra-corporeal perfusion of a porcine hepatic segment. Methods Whole porcine livers were retrieved from animals slaughtered according to UK laws for food production and connected to a normothermic extracorporeal perfusion circuit. Constant perfusion via the hepatic artery and portal vein with heparinized autologous blood was established. Sodium bicarbonate, epoprostanol sodium and calcium chloride were also added to the perfusate to regulate acid-base status and reduce vasospasm. Functionality was assessed by monitoring blood-gases, perfusion pressures and flow rate. A segmental ex-vivo liver resection was performed to leave hepatic segment IV in circuit and isolated segment IV perfusion was maintained for one hour. Results Portal venous pressure was maintained between 8-16mmHg and hepatic arterial pressure between 80-90mmHg. Metabolic acidosis resolved with addition of sodium bicarbonate to the circuit with a pH of 7.42 after segmental perfusion for 1 hour. The lactate increased over the course of the perfusion to 20mmol/L after 1 hour of perfusion, however glucose levels were found to improve with the addition of sodium bicarbonate to the circuit.   Conclusions Isolated segmental perfusion via ex-vivo resection of porcine hepatic segments is technically challenging. Ischaemic-reperfusion injury coupled with progressive metabolic acidosis may limit model viability. However, addition of sodium bicarbonate to the perfusate aids reduction of glucose levels and improves acidosis. Successful perfusion of a porcine hepatic segment provides the potential for segmental perfusion of human hepatic segments such as those resected during hemi-hepatectomies (HRA approved; REC 21/PR/0287). This is an important milestone leading to the creation of a model to study the early changes in human liver tissue for example during infection.  

An experimental model of veno-venous arterial extracorporeal membrane oxygenation

2019 ◽  
Vol 43 (4) ◽  
pp. 268-276
Author(s):  
Mirko Belliato ◽  
Luca Caneva ◽  
Alessandro Aina ◽  
Antonella Degani ◽  
Silvia Mongodi ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Experimental Model ◽  
Ex Vivo ◽  
Venous Pressure ◽  
Ex Vivo Model ◽  
Membrane Oxygenation ◽  
Arterial Cannula ◽  
Venous Cannula ◽  
Custom Made ◽  
Aortic Impedance

Introduction: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. Aim: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump–driven circuit. Methods: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. Results: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. Conclusion: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings

scholarly journals Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Theodoros Kapetanakis ◽  
Ilias I Siempos ◽  
Eugenios I Metaxas ◽  
Petros Kopterides ◽  
George Agrogiannis ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Pilot Study ◽  
Lung Injury ◽  
Ex Vivo ◽  
Hypercapnic Acidosis ◽  
Ex Vivo Model ◽  
Ventilator Induced Lung Injury

scholarly journals Subnormothermic Perfusion with H2S Donor AP39 Improves DCD Porcine Renal Graft Outcomes in an Ex Vivo Model of Kidney Preservation and Reperfusion

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 446
Author(s):  
Smriti Juriasingani ◽  
Aushanth Ruthirakanthan ◽  
Mahms Richard-Mohamed ◽  
Masoud Akbari ◽  
Shahid Aquil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Urine Output ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Autologous Blood ◽  
Expression Patterns ◽  
Graft Function ◽  
Ex Vivo Model ◽  
Kidney Preservation ◽  
Renal Graft

Cold preservation is the standard of care for renal grafts. However, research on alternatives like perfusion at higher temperatures and supplementing preservation solutions with hydrogen sulfide (H2S) has gained momentum. In this study, we investigated whether adding H2S donor AP39 to porcine blood during subnormothermic perfusion at 21 °C improves renal graft outcomes. Porcine kidneys were nephrectomized after 30 min of clamping the renal pedicles and treated to 4 h of static cold storage (SCS) on ice or ex vivo subnormothermic perfusion at 21 °C with autologous blood alone (SNT) or with AP39 (SNTAP). All kidneys were reperfused ex vivo with autologous blood at 37 °C for 4 h. Urine output, histopathology and RNAseq were used to evaluate the renal graft function, injury and gene expression profiles, respectively. The SNTAP group exhibited significantly higher urine output than other groups during preservation and reperfusion, along with significantly lower apoptotic injury compared to the SCS group. The SNTAP group also exhibited differential pro-survival gene expression patterns compared to the SCS (downregulation of pro-apoptotic genes) and SNT (downregulation of hypoxia response genes) groups. Subnormothermic perfusion at 21 °C with H2S-supplemented blood improves renal graft outcomes. Further research is needed to facilitate the clinical translation of this approach.

1849: Systematic Evaluation of 21μm Thulium Laser Device for Treatment of Benign Prostatic Enlargement in an Ex-VIVO Model

2007 ◽  
Vol 177 (4S) ◽  
pp. 614-614 ◽  
Author(s):  
Gunnar Wendt-Nordahl ◽  
Stefanie Huckele ◽  
Patrick Honeck ◽  
Peter Aiken ◽  
Thomas Knoll ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Systematic Evaluation ◽  
Thulium Laser ◽  
Laser Device ◽  
Benign Prostatic Enlargement ◽  
Ex Vivo Model ◽  
Prostatic Enlargement

Porcine small intestine, a good ex vivo model to investigate absorption and metabolism of natural products

2017 ◽  
Author(s):  
J Houriet ◽  
YE Arnold ◽  
C Petit ◽  
YN Kalia ◽  
JL Wolfender
Keyword(s):  
Natural Products ◽  
Small Intestine ◽  
Ex Vivo ◽  
Ex Vivo Model

Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

1995 ◽  
Vol 73 (02) ◽  
pp. 219-222 ◽  
Author(s):  
Manuel Monreal ◽  
Luis Monreal ◽  
Rafael Ruiz de Gopegui ◽  
Yvonne Espada ◽  
Ana Maria Angles ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
In Vitro Study ◽  
Ex Vivo Model ◽  
Suitable Candidate ◽  
Significant Prolongation ◽  
High Doses ◽  
Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

EMR+: Vorstellung einer neuen endoskopischen Resektionsmethode im ex-vivo Model

2019 ◽  
Author(s):  
RF Knoop ◽  
E Wedi ◽  
V Ellenrieder ◽  
A Neesse ◽  
S Kunsch
Keyword(s):  
Ex Vivo ◽  
Ex Vivo Model

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Cartilage Explants ◽  
Ex Vivo Model ◽  
Chondrocyte Viability ◽  
Platelet Concentration ◽  
The Absolute ◽  
Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

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