Volker Unger

A model of isolated autologously hemoperfused porcine slaughterhouse kidneys.

Background: The rapidly evolving field of transplantation research with a focus on ischemic and reperfusion injuries has gained importance since the methodology of organ preservation significantly limits graft survival. Numerous models of isolated perfused kidneys have been established in the past years but limitations such as organ size, perfusate and ethical standards have restricted a widespread research in this area. Methods: A model of hemoperfused isolated porcine slaughterhouse kidneys was established which encompasses the advantages of autologous blood as optimal perfusate and a reduction of animal experiments. Results: The size and geometry of the porcine kidney is more comparable to human conditions and various renal functions, blood parameters and morphology can easily be accessed in the present model. Stable organ function can be maintained over 2 h with an amount of 500–1,000 ml of autologous blood which is metabolically controlled via a dialysis system. Conclusion: In summary, the present model describes a new and economic approach for targeting renal function in transplantation models by combining autologous blood as optimal perfusate with a well-defined organ geometry and function and slaughterhouse animals as a source.

Isolated Hemoperfused Slaughterhouse Livers as a Valid Model to Study Hepatotoxicity

Different models of isolated and perfused livers and precision cut liver slices have been developed for studies on liver toxicology the past years. As most of these models were limited by nonphysiologi c settings, a new model of normothermic hemoperfused isolated porcine slaughterhous e livers to examine hepatotoxicity was established encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. As model compound, the analgesic substance diclofenac was used and the effects of this drug on organ function parameters were compared to an untreated control group. Using an amount of 2,000 ml, the organs were perfused over 180 minutes, metabolically controlled via a dialysis and oxygenation system and various hematological and hepatic parameters were examined. In contrast to the untreated control organs, significant differences were found in the diclofenac group for parameters such as lactate, creatinine, ALT, bicarbonate, or bile flow. In summary, the presently established model of isolated hemoperfused slaughterhouse livers displays a useful new approach to assess hepatotoxicity of different substances on the organ level. As a major economic advantage in comparison to setups using laboratory animals, the new model can be run with blood and organs obtained from slaughterhouse animals.

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.

Mobile air quality studies (MAQS) in inner cities: particulate matter PM10 levels related to different vehicle driving modes and integration of data into a geographical information program

BackgroundParticulate matter (PM) is assumed to exert a major burden on public health. Most studies that address levels of PM use stationary measure systems. By contrast, only few studies measure PM concentrations under mobile conditions to analyze individual exposure situations.MethodsBy combining spatial-temporal analysis with a novel vehicle-mounted sensor system, the present Mobile Air Quality Study (MAQS) aimed to analyse effects of different driving conditions in a convertible vehicle. PM10 was continuously monitored in a convertible car, driven with roof open, roof closed, but windows open, or windows closed.ResultsPM10 values inside the car were nearly always higher with open roof than with roof and windows closed, whereas no difference was seen with open or closed windows. During the day PM10 values varied with high values before noon, and occasional high median values or standard deviation values due to individual factors. Vehicle speed in itself did not influence the mean value of PM10; however, at traffic speed (10 – 50 km/h) the standard deviation was large. No systematic difference was seen between PM10 values in stationary and mobile cars, nor was any PM10 difference observed between driving within or outside an environmental (low emission) zone.ConclusionsThe present study has shown the feasibility of mobile PM analysis in vehicles. Individual exposure of the occupants varies depending on factors like time of day as well as ventilation of the car; other specific factors are clearly identifiably and may relate to specific PM10 sources. This system may be used to monitor individual exposure ranges and provide recommendations for preventive measurements. Although differences in PM10 levels were found under certain ventilation conditions, these differences are likely not of concern for the safety and health of passengers.

Lebertoxizität — molekulare Analyse von Leberfunktionsstörungen in der Arbeitsmedizin und Umweltmedizin

ZusammenfassungDie Leber steht als zentrales Organ der Entgiftung im Zentrum von Effekten exogen zugeführter Substanzen und ist deswegen von entscheidender Bedeutung für die arbeitsmedizinische und umweltmedizinische Toxikologie. Gerade in letzter Zeit wurden Effekte von Nahrungsmittelbestandteilen, wie Acrylamid, kritisch diskutiert. Breitgefächerte Möglichkeiten zur Evaluation hepatotoxischer Effekte sind letztlich zwingend notwendig zur Risikoabschätzung im arbeitsmedizinischen und umweltmedizinischen Bereich. In den letzten Jahren gab es zahlreiche Neuerungen innerhalb des methodischen Spektrums.Diesbezüglich wurden neue ex vivo-Leberperfusionsmodelle und in vitro-Leberschnittmodelle entwickelt. Aufgrund der komplexen Gefäßversorgung stellt die Leber besondere Anforderungen an die Organversorgung innerhalb von Hämoperfusionsmodellen. Der Vorteil dieser Modelle beruht darin, dass die Organfunktion als Ganzes erhalten bleibt und dabei die Effekte beruflicher und umweltbedingter Noxen analysiert werden können.Als neuer wegweisender Ansatz ermöglicht in idealer Weise eine Kombination von Leberperfusionen mit der Vital- Dünnschnitt-Technik und weiterführenden molekularbiologischen, funktionellen sowie histologischen Techniken die Erhebung viel- schichtiger toxikologischer Daten, die weit über die Daten aus konventionellen Tierversuchen oder Zellkulturexperimenten hinausgehen. Dabei können neben der Beurteilung anaboler bzw. kataboler Vorgänge nach Exposition gegenüber exogenen Substanzen darüber hinaus auch Exkretionsmechanismen über die Galle beurteilt werden.SummaryThe liver is the central organ in the detoxification processes of exogenous noxious substances in the human body. It therefore plays a major role in occupational and environmental toxicology. Recently the effects of foodstuffs substances such as acrylamide have been heavily debated. Diverse opportunities to evaluate hepato-toxic effects are needed to fully assess the risk in areas of occupational medicine and environmental medicine. In recent years, many advances have been made with regard to the methods available.Among them, novel ex vivo liver perfusion models and in vitro liver tissue section models have been developed. Due to the complex hepatic vascular distribution, the liver places special demands on the organ supply with regard to hemoperfusion models. The advantage of these models is the preservation of the overall organ function which enables the assessment of diverse effects of occupational and environmental noxious substances.Ideally, a combination of liver perfusion models, vital liver section models and sophisticated functional, molecular and morphological techniques enables the analysis of a broad spectrum of toxicological data, which are far superior to conventional techniques such as animal experiments or cell culture studies. In addition to the assessment of catabolic and anabolic mechanisms after exposure to exogenous substances, functional mechanisms such as bile secretion can also be evaluated.RésuméLe foie, en qualité d’organe central de désintoxication, se trouve au centre d’effets de substances exogènes et revêt par conséquent une importance déterminante pour la toxicologie dans la médecine du travail et la médecine de l’environnement. Depuis un certain temps justement, les effets d’ingrédients de produits alimentaires comme l’acrylamide, font l’objet de discussions critiques. De vastes possibilités d’évaluation des effets hépatotoxiques sont finalement absolument obligatoires afin d’apprécier les risques dans le secteur de la médecine du travail et de l’environnement. Au cours des dernières années, de nombreuses nouveautés sont apparues au niveau des méthodes.A ce propos, de nouveaux modèles ex vivo de perfusion du foie ainsi que des modèles de découpe de foie in vitro ont été mis au point. En raison de la complexité de l’irrigation des vaisseaux, le foie pose des exigences particulières à l’approvisionnement des organes au sein des modèles d’hémoperfusion. L’avantage de ces modèles réside dans le fait que la fonction de l’organe est maintenue dans sa totalité et qu’il est possible ce faisant d’analyser les effets de toxines de nature professionnelle et environnementale.Idéalement, une combinaison des perfusions du foie avec la technique Vital de coupe fine et d’autres techniques biomoléculaires, fonctionnelles et histologiques, constitue une nouvelle approche prometteuse qui permet de recueillir de nombreuses données toxicologiques qui vont bien au-delà des données obtenues par le biais d’expériences animales traditionnelles ou de tests de culture de cellules. Cela permet, outre une évaluation des processus anaboliques voire cataboliques après une exposition à des substances exogènes, d’étudier également les mécanismes d’excrétion par le biais de la vésicule biliaire.