Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors.

Liver cells cultured in 3D bioreactors is an interesting option for temporary extracorporeal liver support in the treatment of acute liver failure and for animal models for preclinical drug screening. Bioreactor capacity to eliminate drugs is generally used for assessing cell metabolic competence in different bioreactors or to scale-up bioreactor design and performance for clinical or preclinical applications. However, drug adsorption and physical transport often disguise the intrinsic drug biotransformation kinetics and cell metabolic state.

C-Reactive Protein Causes Blood Pressure Drop in Rabbits and Induces Intracellular Calcium Signaling.

Systemic diseases characterized by elevated levels of C-reactive protein (CRP), such as sepsis or systemic inflammatory response syndrome, are usually associated with hardly controllable haemodynamic instability. We therefore investigated whether CRP itself influences blood pressure and heart rate. Immediately after intravenous injection of purified human CRP (3.

Increased compensatory kidney workload results in cellular damage in a short time porcine model of mixed acidemia - Is acidemia a 'first hit' in acute kidney injury?

Acute kidney injury (AKI) corrupts the outcome of about 50% of all critically ill patients. We investigated the possible contribution of the pathology acidemia on the development of AKI. Pigs were exposed to acidemia, acidemia plus hypoxemia or a normal acid-base balance in an experimental setup, which included mechanical ventilation and renal replacement therapy to facilitate biotrauma caused by extracorporeal therapies.

Feasibility study of an active wound dressing based on hollow fiber membranes in a porcine wound model.

Investigation: A novel active wound dressing (AWD) concept based on a microporous hollow fiber membrane network was investigated in an animal model. It provides a local solution-perfused environment for regenerative cell nutrition, wound irrigation, debris removal, electrolyte balancing, pH regulation, and topical antibiosis. The device is capable of supplying soluble factors, as tested experimentally for the recombinant human growth and differentiation factor-5 (rhGDF-5).

Selective apheresis of C-reactive protein: a new therapeutic option in myocardial infarction?

Background: There is substantial evidence that C-reactive protein (CRP) mediates secondary damage of the myocardium after acute myocardial infarction (AMI). The aim of this animal trial in pigs was to specifically deplete CRP from porcine plasma after AMI and to study possible beneficial effects of the reduced CRP concentration on the infarcted area.

Methods: Ten pigs received balloon catheter-induced myocardial infarction.

Impact of different types of resuscitation fluids on coagulation and continuous venovenous hemofiltration hemocompatibility in a porcine model.

Intensive therapy demanding diseases (organ failure or sepsis) are assumed to be the etiology behind a decreased biocompatibility of extracorporeal systems for renal replacement therapy (RRT). There are also potential interactions between different components of the overall therapy. Volume substitutes are known to influence hemorheology and coagulation.

Adverse influence of mixed acidemia on the biocompatibility of continuous veno-venous hemofiltration with respect to the lungs.

Experimental data indicate that hypercapnic adidosis has anti-inflammatory effects. These anti-inflammatory effects may even be a beneficial property in case of low tidal volume ventilation with consecutive hypercapnic acidosis. It is unclear whether these anti-inflammatory effects predominate in critically ill patients who suffer from multiple pro- and anti-inflammatory insults like extracorporeal organ support (pro-inflammatory), metabolic acidosis (pro- and anti-inflammatory), as well as hypoxia (pro-inflammatory).

First level prevention instead of third level intervention-review of research to improve biocompatibility and performance of capillary membrane apheresis in critically ill patients.

In intensive care medicine, convection-based apheresis is of growing interest. Applying extracorporeal systems in the critically ill patient can cause severe complications like nosocomial infections and bleeding, which can be worsened or even initialized by the anticoagulation protocol used. Furthermore, the filter modules (hemo- and plasmafilters) often tend to a fast blockage.

Evaluation of a new large animal model for controlled intracranial pressure changes induced by capnoperitoneum.

Background: A standardized large animal model for controlled ICP manipulation within a relevant range and repetitive ICP measurements is missing. We sought to develop such a model on the base of controlled IPP changes induced by capnoperitoneum.

Methods: We utilized six female pigs (mean body weight 59.

In a porcine model of mixed acidemia HES 130/0.4 may support more stable hemodynamics during CVVH when compared to gelatine.

Purpose: Continuous veno-venous hemofiltration (CVVH) and mixed acidemia often occur simultaneously in critically ill patients. In a previous study in non-acidemic pigs we found that colloids and CVVH interact specifically with respect to hemodynamic stability, with favorable effects for 6% HES 130/0.4 versus 4% gelatine (GEL) infusion.

Experimental high-volume hemofiltration with predilutional tris-hydroxymethylaminomethane for correction of low tidal volume ventilation-induced acidosis.

The most common method of controlling acidemia during lung-protective ventilation is CO₂ removal with an extracorporeal lung assist (ECLA) system. Another possibility to prevent acidemia is based on intravenous (i.v.

Stable mixed acidemia in anesthetized pigs--a model for research on biocompatibility of hemofilters under a deteriorated acid-base balance.

In recent years, acidosis has been of growing interest in intensive care medicine. Most animal models only provide a short-term investigation of the effects of acidosis. They are not suitable for research on interactions with extracorporeal organ support (here continuous venovenous hemofiltration, CVVH).

Specific removal of C-reactive protein by apheresis in a porcine cardiac infarction model.

Background: C-reactive protein (CRP) is a possible causative factor of the destructive processes observed during the weeks after myocardial infarction.

Methods: We developed a clinically relevant animal model including the removal of CRP from blood plasma utilizing a specific CRP adsorber and the visualization of the infarct scar in the living animal by cardiovascular magnetic resonance imaging as a tool to investigate the impact of CRP after acute myocardial infarction.

Results: We describe the facets of this model system and kinetics of clinical blood parameters like CRP and troponin.

Prolonged hypoxemia and acidemia in anesthetized pigs: a model for research on extracorporeal organ support in an intensive care setting.

Purpose: Hypoxemia and acidemia (hypoxemia/acidemia) are serious complications in the critically ill and often occur in unstable patients exposed to extracorporeal organ support. Still, little is known about the biocompatibility interactions of hypoxemia/acidemia with extracorporeal circuits (ECC). Existing animal models often include the release of mediator cascades (sepsis-, lung injury models) or are based on small laboratory animals.

Influence of acidaemia and hypoxaemia on CVVH haemocompatibility in a porcine model.

Background: Reduced haemocompatibility and early filter failure during continuous venovenous haemofiltration (CVVH) can be attributed to various aspects from filter engineering to rheological problems. Still, little is known about the impact of acidaemia and hypoxaemia on the haemocompatibility of a CVVH. In a porcine model, we investigated blood and coagulation parameters, filter performance and blockage of filter capillaries to assess the impact of acidaemia and hypoxaemia on haemocompatibility.

Six percent hydroxyethyl starch 130/0.4 impacts differently on blood glucose than 4% gelatine in a swine model of mixed acidaemia.

Background: Tris-hydroxymethyl aminomethane can be used as a buffer in case of restricted ventilation, but hypoglycaemia is one adverse effect. The influence of a starch-based colloid [6% hydroxyethyl starch 130 kDa/0.4 (HES130)] vs.

Duodenal motility is not affected during duodenotomy in pigs.

The effects of surgical procedures on intestinal motility are still under debate. In order to quantify the effects of duodenotomy on duodenal motility, the present study used the electric impedance technique (IMP). Ten pigs (32-40 kg) were instrumented under general anaesthesia with a central venous catheter (CVC) and a percutaneous enterogastrostomy (PEG).

Hydroxyethyl starch 130 kd/0.4 and albumin improve CVVH biocompatibility whereas gelatin and hydroxyethyl starch 200 kd/0.5 lead to adverse side effects of CVVH in anesthetized pigs.

Unlabelled: Both fluid management and renal replacement therapies play a fundamental role in the treatment of critically ill patients. In a recent in vitro study, we have shown specific interactions of different colloids and the hemocompatibility of hemofilters. The present study was performed to compare the five most common fluids for volume resuscitation, i.

Relation of haemofilter type to venous catheter resistance is crucial for filtration performance and haemocompatibility in CVVH--an in vitro study.

Background: Main factors for the overall performance of haemofilters (HF) are membrane features and filter durability without clogging/clotting of capillaries. However, the venous line resistance (Pv) is a powerful force for net filtrate flux resulting in haemoconcentration and thus is enhancing the phenomenon of membrane clogging. Therefore, we hypothesized that catheter type, as it is associated with Pv-levels, contributes to the extent in which filter longevity and filtration performance are restricted due to blocked hollow fibres.

Albumin and hydroxyethyl starch 130 kDa/0.4 improve filter clearance and haemocompatibility in haemo- and plasmafiltration--an in vitro study.

Background: Apart from their standard applications, haemofiltration (HF) and plasmafiltration (PF) may provide helpful therapy for sepsis, multiple organ- and acute liver-failure. Some colloids cause either decreases or increases in blood cell agglomeration. We hypothesized that solutions which reduce cell aggregability may lead to both improved filter clearance and better haemocompatibility due to decreasing rates of clogged hollow fibres.

Impact of inverse plasma filtration on complement activation in porcine blood.

During extracorporeal circulation, activation of the complement system as a bioincompatibility reaction upon contact with artificial surfaces is well known. This may induce adverse effects for the patient as well as for the bioreactor when using a hybrid liver support system. At present, the achievable clearance rates in hybrid liver support systems are restricted by the limitations of blood flow through the capillaries of the plasma filter.

Influence of different heparin concentrations on the results of in vitro investigations in plasmaseparation technology using capillary membrane filters.

Capillary membrane filters are devices commonly used for plasmapheresis and recirculating detoxification systems, including plasmaseparation units. Besides clinical trials and case reports, research on plasmafiltration techniques is carried out using in vitro systems. Notably, such hemoperfused in vitro systems require anticoagulation protocols suitable for investigating the clearance performance and hemocompatibility of a plasmafilter.