Temperatures in Pigs During 3 T MRI Temperatures, Heart Rates, and Breathing Rates of Pigs During RF Power Deposition in a 3 T (128 MHz) Body Coil.

Exposure to radiofrequency (RF) power deposition during magnetic resonance imaging (MRI) induces elevated body-tissue temperatures and may cause changes in heart and breathing rates, disturbing thermoregulation. Eleven temperature sensors were placed in muscle tissue and one sensor in the rectum (measured in 10 cm depth) of 20 free-breathing anesthetized pigs to verify temperature curves during RF exposure. Tissue temperatures and heart and breathing rates were measured before, during, and after RF exposure. Pigs were placed into a 60-cm diameter whole-body resonator of a 3 T MRI system. Nineteen anesthetized pigs were divided into four RF exposure groups: sham (0 W/kg), low-exposure (2.7 W/kg, mean exposure time 56 min), moderate-exposure (4.8 W/kg, mean exposure time 31 min), and high-exposure (4.4 W/kg, mean exposure time 61 min). One pig was exposed to a whole-body specific absorption rate (wbSAR) of 11.4 W/kg (extreme-exposure). Hotspot temperatures, measured by sensor 2, increased by mean 5.0 ± 0.9°C, min 3.9; max 6.3 (low), 7.0 ± 2.3°C, min 4.6; max 9.9 (moderate), and 9.2 ± 4.4°C, min 6.1, max 17.9 (high) compared with 0.3 ± 0.3°C in the sham-exposure group (min 0.1, max 0.6). Four time-temperature curves were identified: sinusoidal, parabolic, plateau, and linear. These curve shapes did not correlate with RF intensity, rectal temperature, breathing rate, or heart rate. In all pigs, rectal temperatures increased (2.1 ± 0.9°C) during and even after RF exposure, while hotspot temperatures decreased after exposure. When rectal temperature increased by 1°C, hotspot temperature increased up to 42.8°C within 37 min (low-exposure) or up to 43.8°C within 24 min (high-exposure). Global wbSAR did not correlate with maximum hotspot. Bioelectromagnetics. 2021;42:37-50. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.

How can we achieve infection-resistant percutaneous energy transfer?

Clinical records show ever increasing functional times of rotary blood pumps implanted in patients. With longer functional time, the problem of driveline infection is becoming more urgent. No material or scaffold has been found, which allows a permanent and stable ingrowth of skin cells that would prevent (pathogenic) germs entering the body. Usually, the epithelial cells die at the exit site and new cells form a sulcus around the driveline, which grows deeper and finally becomes infected. The purpose of this project is to present a solution to this problem by elaborating a new mechanism, the active skin-penetrating device. The device is composed of a tube with a 5-mm diameter, a protective sleeve that surrounds the catheter exit site, and an active traction device. The protective sleeve is made of thin polyurethane covered with polyethylenterephtalat (PET, i.e. Dacron) fibers to permit the attachment of keratinocytes, similar to the standard driveline. The active traction device exerts a constant pull on the protective sleeve. The ingrown keratinocytes slowly give way and the protective sleeve gradually moves out of the body at a rate of a few millimeters per week. Meanwhile, the keratinocytes transform into horny cells and are then shed as in natural skin. Therefore, the formation of a sulcus is avoided, and the protective sleeve remains infection-free. In a first proof of the concept, four of the new devices and 10 control devices were implanted in goats. The devices remained infection-free for a period of 420 days, whereas four of the 10 control devices became infected. On the basis of these experiments, the active skin-penetrating device has been further developed and is being tested again in goats in a refined version. The results so far indicate that with the active-skin penetrating device an infection-resistant percutaneous energy transfer can be achieved for a prolonged period of time.

The Influence of Different Auditory Stimuli on Attentiveness and Responsiveness in Road Traffic in Simulated Traffic Situations.

The use of portable media has become an integral part of our increasingly mobile society. The use of digital audio books is also growing steadily in Germany. The connection between the psychological effect of music of different volumes and rhythms and the change in reaction in road traffic with a corresponding increase in risk behavior, especially when driving, has already been proven in previous studies. Only a few studies are available on the effects of listening to radio plays on reaction behavior and concentration in road traffic as well as on risk behavior among pedestrians and cyclists. In the present study, we have investigated the influences of pop music and a radio play on reaction behavior and thus driving ability during the execution of a traffic psychological test series from the "Wiener Test System". The central topic deals with the performance of the test subjects in the individual tests. Conclusions are drawn on the reaction behavior and concentration during participation in road traffic and thus the risk of distraction and possible increased risk of accidents. Studies on the influence of auditory stimuli and their effects on concentration and reaction during participation in traffic are of great interest from the point of view of traffic psychology and occupational medicine, since a reduction in the risk of accidents can increase general traffic safety and lead to a decrease in sick leave and therefore fewer absences from work.

[Introduction of a MR-compatible system for extracorporal perfusion of vital organs for MR-guided procedures--first-experiences]. / Einsatz eines MR-kompatiblen Organperfusionssystems für physiologische Ex-vivo-Experimente im MRT--Erste Erfahrungen mit einem Tierversuchsersatzsystem.

PURPOSE: To represent a MRI-compatible perfusion-system for extracorporeal perfusion of vital organs which permits the realisation of realistic experiments in a MR scanner. MATERIAL AND METHODS: We performed MR examinations of explanted porcine livers and MR-guided interventions in porcine livers. Explanted organs were hemo-perfused under physiological conditions during the experiments. MR-sequences for diagnostic and interventional examinations were used. RESULTS: The evaluated system was MRI-compatible. The achieved image quality of the used sequences showed excellent anatomical resolution. Planned experiments can be carried out with relatively low expenditure. Diagnostic as well as interventional investigations can be carried out. The used organs showed a stable function within physiological parameters up to 4 hours. CONCLUSION: It is possible to perform ex vivo experiments under in vivo conditions with this system. With the used MR-compatible system MR-guided experimental interventions and thermal ablations can be carried out in explanted organs under in vivo conditions.

Haemoperfused liver as an ex vivo model for organ invasion of Candida albicans.

To study invasion of the human fungal pathogen Candida albicans, several infection models have been established. This study describes the successful establishment of an ex vivo haemoperfused liver as a model to study invasion of C. albicans. Perfused organs from pigs could be kept functional for up to 12 h. By comparing a non-invasive and invasive strain of C. albicans and by following a time course of invasion, it was shown that the invasion process in the perfused liver infection model is very similar to the in vivo situation after intraperitoneal infection of mice. The advantage of this set-up compared with other models of invasion is discussed.

Novel silk protein barrier membranes for guided bone regeneration.

This study assesses the biocompatibility of novel silk protein membranes with and without modification, and evaluates their effect on facilitating bone formation and defect repair in guided bone regeneration. Two calvarian bone defects 12 mm in diameter were created in each of a total of 38 rabbits. Four different types of membranes, (silk-, hydroxyapatite-modified silk-, ß-TCP-modified silk- and commonly clinically used collagen-membranes) were implanted to cover one of the two defects in each animal. Histologic analysis did not show any adverse tissue reactions in any of the defect sites indicating good biocompatibility of all silk protein membranes. Histomorphometric and histologic evaluation revealed that collagen and ß-TCP modified silk membranes supported bone formation (collagen: bone area fraction p = 0.025; significant; ß-TCP modified silk membranes bone area fraction: p = 0.24, not significant), guided bone regeneration and defect bridging. The bone, which had formed in defects covered by ß-TCP modified silk membranes, displayed a more advanced stage of bone tissue maturation with restoration of the original calvarial bone microarchitecture when compared to the bone which had formed in defects, for which any of the other test membranes were used. Micro-CT analysis did not reveal any differences in the amount of bone formation between defects with and without membranes. In contrast to the collagen membranes, ß-TCP modified silk membranes were visible in all cases and may therefore be advantageous for further supporting bone formation beyond 10 weeks and preventing soft tissue ingrowth from the periphery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2603-2611, 2017.

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.e., normal saline (SAL), hydroxyethyl starch 130 kd/0.4 (HES130), hydroxyethyl starch 200 kd/0.5 (HES200), albumin (ALB), and gelatin (GEL) with respect to their interaction with continuous venovenous hemofiltration (CVVH) in anesthetized domestic pigs. METHODS: Animals (n = 63) were allocated randomly to the fluid type and the respective subgroups, which were divided into control and CVVH groups (n = 6 ndash; 7 per group). Bolus infusion of group specific fluid was followed by a bolus of heparin and the initiation of hemofiltration in CVVH groups. Thereafter, fluids were infused at constant rates, and heparin application was adjusted to keep the activated clotting time at 200 to 250 s. Hemodynamics, airway pressures, pulmonary gas exchange, diuresis, creatinine clearance, and blood cell counts were investigated during the entire procedure (10 ndash; 12 hours). RESULTS: Basics of in vivo effects of SAL, HES130, and ALB were not altered during CVVH. HES130 and ALB enabled stable hemocompatibility, diuresis, and hemodynamics in the respective groups. In contrast, organ functions were significantly different between control and CVVH groups when animals were treated with GEL or HES200. In particular, during CVVH, HES200 led to reduced platelet counts, deteriorated hemodynamics, and increasing airway pressures during CVVH. GEL led to increasing airway pressures, a decrease in pulmonary gas exchange, deteriorated hemodynamics, altered renal histomorphology, reduced platelet counts, and reduced hemoglobin. CONCLUSIONS: Direct in vivo effects of colloids in anaesthetized and ventilated pigs are not predictable for their effects during CVVH. Interaction between CVVH and every volume substitute occur in a highly specific manner. This observation could be helpful to explain contradictory study results and should be considered for future study designs.

Evaluation of renal functional parameters in different settings of isolated organ hemoperfusions.

Isolated porcine kidneys are commonly used to study physiological and pathophysiological aspects of renal homeostasis but standardized evaluation procedures of renal function in this model do not exist so far. A double-logarithmical nomogram is established for filtration and reabsorption functions in isolated and hemoperfused porcine kidneys using different perfusion settings. Model validity was demonstrated by the levels of urine flow and sodium excretion showing expected alteration levels of lowering in the ADH-group and increasing in the furosemide-group of isolated kidneys. Creatinine-clearance values were in constant ranges within each specific perfusion group as indicated by the nomogram procedure. The present studies used a nomogram method to analyze the effects of different renal perfusion settings in a porcine model of kidney perfusion. The method may be of use to differentiate various kidney perfusion parameters both at the experimental and clinical levels.

Bionic approach for the prevention of exit-site infections of percutaneous devices.

Exit-site infections remain one of the main complications for percutaneous devices, such as catheters for peritoneal dialysis or drivelines for ventricular assist devices. Many efforts have been made to create a biological seal, yet without long-term success. This study investigates a new kind of percutaneous device which is coated with an extricable polymeric membrane. The bionic approach applies the naturally outwards directed growth of skin structures to technology: by pulling the protective membrane it slowly grows out of the body and a developing sulcus is exposed to dry air and an infection is avoided. In a feasibility study this kind of device was shown to reduce the rate of infection. To further investigate these devices, they were implanted in the skin of goats and observed for a period of more than 500 days. The membranes were pulled with a force of up to 2 N and the resulting movement was recorded. When being pulled, the membranes moved 0.4-0.9 mm per week, showing that the application of a continuously acting, defined force on the protective membrane causes the desired slow movement.

Influence of cold storage on renal ischemia reperfusion injury after non-heart-beating donor explantation.

BACKGROUND: Due to the increasing need for kidney donors, transplantation from non-heart-beating donors (NHBD) is currently being practiced more extensively. As detailed studies on the reperfusion injury of these kidneys do not exist so far, a comparison of renal ischemia reperfusion injury scores immediately after organ explantation with injury scores after NHBD organ explantation with subsequent cold storage would be useful. METHODS: Non-stored kidneys were compared to a group of kidneys stored for 6.9 +/- 1.8 h. Functional analyses were made during 145 min of ex vivo perfusion. Quantitative histological analyses were performed in all kidneys after termination of perfusion. RESULTS: During ex vivo reperfusion, renal vascular resistance was elevated, while creatinine clearance, filtration fraction, renal oxygen consumption, and sodium reabsorption were below normal after non-heart-beating explantation and further decreased after subsequent washing and cold storage. In the kidneys subjected to cold preservation, histologically tubular damage was enhanced, and the total count, as well that for the intraglomerular neutrophil granulocytes were also elevated. CONCLUSIONS: Explantation from NHBD causes renal ischemia reperfusion injury. Cold storage augmented deterioration of the kidney as histologically and functionally demonstrated. Thus, preservation times for non-heart-beating kidneys should be carefully reappraised.

Hemoperfused isolated porcine slaughterhouse kidneys as a valid model for pharmacological studies.

Mammalian models of isolated perfused kidneys provide an important tool to study pharmacological, toxicological, and physiological properties of drugs, hormones, and vasoactive substances. As organs from small laboratory animals are difficult to compare to human conditions, porcine and bovine kidneys permit better approaches to simulate human conditions. We developed an alternative model for pharmacological studies using isolated hemoperfused porcine kidneys from slaughterhouse animals to reduce laboratory animal experiments. Controlled pharmacological studies were established using furosemide (2 mg/100 g organweight) as a model drug. Kidneys were hemoperfused after a preservation period of 4.6 +/- 1.7 h. In comparison to the control period, furosemide application led to significant changes in renal parameters with urine flow: 4.2/1.7 mL/min*100 g (furosemide/control), urine-sodium: 108/77.5 mmol/L, sodium excretion: 0.47/0.14 mmol/min*100 g; all differences significant, p < 0.01. The parameters stabilized to normal values as found in the control period within a period of 80 min. A second group of laboratory-harvested kidneys was examined for differences and revealed limitations of the slaughterhouse organs in parameters such as oxygen consumption. In summary, the present study demonstrates the valid use of hemoperfused slaughterhouse kidneys as a pharmacological model of renal function within the limits of the use of slaughterhouse organs, and indicates that future studies using this alternative approach could reduce animal experiments.

Protective effects of B2 preservation solution in comparison to a standard solution (histidine-tryptophan-ketoglutarate/Bretschneider) in a model of isolated autologous hemoperfused porcine kidney.

Reperfusion injuries after organ transplantation affect graft function and influence long-term graft survival. As hypothermic storage, which minimizes the extent of unspecific tissue injury after ischemia and reperfusion, is significantly influenced by the composition of preservation solutions, strategies to optimize the different components may lead to longer graft survival. In the present study the effects of the preservation solution B2 on early renal function and histopathological changes were compared to histidine-tryptophan-ketoglutarate solution (HTK, Bretschneider) in a model of isolated blood-perfused porcine kidneys. B2-preserved kidneys displayed a lower renal resistance and significantly better creatinine clearance as compared to HTK. Mean differences were also found for filtration fraction and sodium fraction reabsorption. The functional data were also related to histopathological changes. Together, these data indicate that the recently developed preservation solution B2 offers new principles of preservation and is a useful preservation solution for experimental isolated perfused kidney models. B2 may also be an interesting model for optimizing preservation within other organ perfusion models.

A model of isolated, autologously hemoperfused porcine slaughterhouse lungs.

INTRODUCTION: Models of isolated and perfused lungs study pathophysiological phenomena of the airways, but are limited by restricted resemblance to the human situation, non-physiological perfusates or the need for the use of high numbers of laboratory animals. The present model was established to address these difficulties. OBJECTIVES: Aim of the current study was the establishment of an animal model that uses slaughterhouse animals and closely resembles physiological conditions found in humans. METHODS: We used a model of hemoperfused isolated porcine slaughterhouse lungs using autologous blood, metabolically controlled via a dialysis system. Over a period of 135 minutes positive inspiratory pressure, pulmonary arterial pressure, pulmonary vein oxygen partial pressure and lung weight were assessed. RESULTS: Stable organ function was maintained over 135 minutes with an amount of 2,500-3,000 ml perfusate without fall in pulmonary arterial pressure. During the time the positive inspiratory pressure and lung weight increased, while pulmonary vein oxygen partial pressure decreased. CONCLUSIONS: The present model of isolated hemoperfused slaughterhouse lungs displays a useful new and economic approach to evaluate pulmonary function and toxicity of different substances on an organ level. As a major economic advantage in comparison to models using laboratory animals, the current model might be run using blood and organs obtained from slaughterhouse animals.

Absolute quantification of regional renal blood flow in swine by dynamic contrast-enhanced magnetic resonance imaging using a blood pool contrast agent.

AIM: To evaluate for the first time in an animal model the possibility of absolute regional quantification of renal medullary and cortical perfusion by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a blood pool contrast agent. MATERIAL AND METHODS: A total of 18 adult female pigs (age, 16-22 weeks; body weight, 45-65 kg; no dietary restrictions) were investigated by DCE-MRI. Absolute renal blood flow (RBF) measured by an ultrasound transit time flow probe around the renal vein was used as the standard of reference. An inflatable stainless cuff placed around the renal artery near its origin from the abdominal aorta was used to reduce RBF to 60%, 40%, and 20% of the baseline flow. The last measurement was performed with the cuff fully reopened. Absolute RBF values during these 4 perfusion states were compared with the results of DCE-MRI performed on a 1.5-T scanner with an 8-channel phased-array surface coil. All scans were acquired in breath-hold technique in the coronal plane using a field of view of 460 mm.Each dynamic scan commenced with a set of five 3D T1-weighted gradient echo sequences with different flip angles (alpha = 2 degrees, 5 degrees, 10 degrees, 20 degrees, 30 degrees): TE, 0.88 milliseconds; TR, 2.65 milliseconds; slice thickness, 8.8 mm for 4 slices; acquisition matrix, 128 x 128; and acquisitions, 4. These data served to calculate 3D intrinsic longitudinal relaxation rate maps (R10) and magnetization (M0). Immediately after these images, the dynamic 3D T1-weighted gradient echo images were acquired with the same parameters and a constant alpha = 30 degrees, half Fourier, 1 acquisition, 64 frames, a time interval of 1.65 seconds between each frame, and a total duration of 105.6. Three milliliters of an albumin-binding blood pool contrast agent (0.25 mmol/mL gadofosveset trisodium, Vasovist, Bayer Schering Pharma AG, Berlin, Germany) was injected at a rate of 3 mL/s. Perfusion was calculated using the arterial input function from the aorta, which was extracted from the dynamic relaxation rate change maps and perfusion images were calculated on a voxel-by-voxel basis using a singular value decomposition. RESULTS: In 11 pigs, 4 different perfusion states were investigated sequentially. The reduced kidney perfusion measured by ultrasound highly correlated with total renal blood flow determined by DCE-MRI, P < 0.001. The correlation coefficient between both measurements was 0.843. Regional cortical and medullary renal flow was also highly correlated (r = 0.77/0.78, P < 0.001) with the degree of flow reduction. Perfusion values smaller than 50 mL/min/100 cm were overestimated by MRI, high perfusion values slightly underestimated. CONCLUSION: DCE-MRI using a blood pool contrast agent allows absolute quantification of total kidney perfusion as well as separate determination of cortical and medullary flow. The results show that our technique has sufficient accuracy and reproducibility to be transferred to the clinical setting.

Reference values and physiological characterization of a specific isolated pig kidney perfusion model.

BACKGROUND: Models of isolated and perfused kidneys are used to study the effects of drugs, hazardous or toxic substances on renal functions. Since physiological and morphological parameters of small laboratory animal kidneys are difficult to compare to human renal parameters, porcine kidney perfusion models have been developed to simulate closer conditions to the human situation, but exact values of renal parameters for different collection and perfusion conditions have not been reported so far. If the organs could be used out of regular slaughtering processes animal experiments may be avoided. METHODS: To assess renal perfusion quality, we analyzed different perfusion settings in a standardized model of porcine kidney hemoperfusion with organs collected in the operating theatre (OP: groups A-D) or in a public abattoir (SLA: group E) and compared the data to in vivo measurements in living animals (CON). Experimental groups had defined preservation periods (0, 2 and 24 hrs), one with additional albumin in the perfusate (C) for edema reduction. RESULTS: Varying perfusion settings resulted in different functional values (mean +/- SD): blood flow (RBF [ml/min*100 g]: (A) 339.9 +/- 61.1; (C) 244.5 +/- 53.5; (D) 92.8 +/- 25.8; (E) 153.8 +/- 41.5); glomerular filtration (GFR [ml/min*100 g]: (CON) 76.1 +/- 6.2; (A) 59.2 +/- 13.9; (C) 25.0 +/- 10.6; (D) 1.6 +/- 1.3; (E) 16.3 +/- 8.2); fractional sodium reabsorption (RFNa [%] (CON) 99.8 +/- 0.1; (A) 82.3 +/- 8.1; (C) 86.8 +/- 10.3; (D) 38.4 +/- 24.5; (E) 88.7 +/- 5.8). Additionally the tubular coupling-ratio of Na-reabsorption/O2-consumption was determined (TNa/O2-cons [mmol-Na/mmol- O2] (CON) 30.1; (A) 42.0, (C) 80.6; (D) 17.4; (E) 23.8), exhibiting OP and SLA organs with comparable results. CONCLUSION: In the present study functional values for isolated kidneys with different perfusion settings were determined to assess organ perfusion quality. It can be summarized that the hemoperfused porcine kidney can serve as a biological model with acceptable approximation to in vivo renal physiology, also if the organs originate from usual slaughtering processes.

The toxicity of cadmium and resulting hazards for human health.

Cadmium (Cd) has been in industrial use for a long period of time. Its serious toxicity moved into scientific focus during the middle of the last century. In this review, we discuss historic and recent developments of toxicological and epidemiological questions, including exposition sources, resorption pathways and organ damage processes.

An improved model of isolated hemoperfused porcine livers using pneumatically driven pulsating blood pumps.

Existing liver perfusion models are largely limited by high degrees of ischemic and reperfusion injury and the lack of standardization. To establish a highly standardized perfusion model and minimize reperfusion injury, a porcine liver perfusion model was developed using an artificial heart pump (Buecherl Artificial Heart). This model is characterized by pneumatically driven and pressure controlled blood pumps with pulsating flow characteristics. The perfusion parameters and the integrity of the perfused organ were assessed using hemodynamic and hepatic function tests. In eight porcine liver perfusion experiments the system allowed maintaining stable and physiologic organ function over 3 hours by bile production (5.5 +/- 3.1 ml/30 minutes, resp. 22.9 +/- 8.4 ml cumulative at 180 minutes), oxygen consumption (2.2 +/- 0.2 ml/min/100 g overall mean) and significantly better liver enzyme levels (AST 19.5 +/- 10.1 U/l/100 g, ALT 2.1 +/- 0.8 U/l/min, LDH 57.8 +/- 24.2 U/l/100 g) compared to previous studies. It was also possible to reduce the circulating blood volume to 1,000 ml and to create a compact perfusion system that is adoptable to other organ systems such as the kidneys. The compact size and the absence of magnetic components also allow a use for advanced imaging techniques. In conclusion this optimized perfusion system provides a sound basis for future studies in the area of hepatotoxicity and pharmacology.

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. METHODS: Heparinized porcine blood (5 IU/ml) was used in an in vitro circuit. The filter types tested were from GAMBRO: HF66D (effective membrane surface: 0.6 m2) and PF1000N (effective membrane surface: 0.15 m2). Albumin (ALB), hydroxyethyl starch (HES) 200/0.5, HES 130/0.4, gelatin (GEL) or normal saline (0.9%) were added to the blood (n = 6/group). Recirculation systems were run for 2 h. Spontaneous haemolysis and filter resistance >420 mmHg were selected as indications of maximal flow rates. Sieving coefficients were determined for 17 parameters at the lowest and highest blood flows and filtration rate. RESULTS: Based on the filter types used, supplementation of ALB and HES130/0.4 led to an improved filter clearance without increasing the number of clogged capillary membranes or causing impaired haemocompatibility. Sieving coefficients for most solutes were independent of volume substitute and flow rate. Haemocompatibility and filter clearance deteriorated after addition of HES200 or GEL to the blood. CONCLUSIONS: Under standardized in vitro conditions, we found that colloids which reduce cell aggregability cause improved HF- and PF-performance. This phenomenon may provide new options for higher clearances and may lead to new concepts in low dose anticoagulation.

In vitro models to study hepatotoxicity.

Drug discovery and development consists of a series of processes starting with the demonstration of pharmacological effects in experimental cell and animal models and ending with drug safety and efficacy studies in patients. A main limitation is often the unacceptable level of toxicity with the liver as the primary target organ. Therefore, approaches to study hepatic toxicity in the early phase of drug discovery represent an important step towards rational drug development. A variety of in vitro liver models have been developed in the past years. Next to their use in drug development, they can also be applied to study environmental toxins and their hepatotoxicity. The 3 main approaches are ex vivo isolated and perfused organ models, precision-cut liver slices and cell culture models. Although the advantage of whole organ perfusions is based on the assessment of physiologic parameters such as bile production and morphologic parameters such as tissue histology, cell culture models can be efficiently used to assess cellular metabolism, cytotoxicity and genotoxicity. The advantage of precision-cut liver slices is based on the juxtaposition of cellular assays and tissue morphology. None of these models can be compared as they all focus on different fields of hepatoxicology. For the future, the ideal setup for testing the hepatic toxicity of a new compound could of primary studies in cell or slice cultures to assess cellular effects and secondary studies using ex vivo perfused organs to examine gross organ function parameters and histology.