38th Scientific
Meeting (GV - SOLAS)
Society for Laboratory Animal Science
(Essen, 2000)
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38th Scientific
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(Essen, 2000) |
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to Abstracts Advantages and limitations of isolated organs - Proceedings of a Workshop (Hamburg, 1998) ¶ Wolfgang F. Pittermann Henkel KGaA, D - 40191 Duesseldorf During the last decade a wide range of isolated organ systems have been developed in biomedical research. Sophisticated equipment, increasing manual skill, routine and standardisation have led to an increase of validity and precision of experimental results under circumstances that are virtually ´true-to-life´. Today these systems contribute a considerable amount of in-vitro knowledge to the scientific community. Promoting animal welfare on all fields of laboratory animal science the Society for Laboratory Animal Science (GV-SOLAS) has decided to organise a workshop during the 36th Scientific Meeting in Hamburg (Sept. 1998) dealing with the development and definition of perfused isolated organ systems. Table1  Table 1 shows the species, the relevant organs including basic information and the locations of the contributing research groups. At the workshop results of other perfused models such as uterus and small intestine were presented too. Generally in some of the systems the perfusate is repeatedly used (reperfusion). Regarding the haemoglobin content the perfusate may be cell free or contains cell such as erythrocytes. The actual proceedings (eds.: W. Pittermann, M. Kietzmann, C. Grosse-Siestrup; published by Laboratory Animals Ltd. (2000); ISBN 0-901334-12-X) contain 23 contributions describing different aspects of the methodology and applications. For cosmetic research (efficacy / safety) under in-vitro conditions the main target areas are skin (follicular skin of porcine leg, porcine ear and bovine udder, / afollicular skin of the bovine udder) and mucous membranes (cisterna of the udder teats) but eyes (cornea), or parts of the airways (tracheal, bronchial) may be exposed under certain circumstances. Advantages and limitations of perfused isolated organs The Fig. 1 presents the position of isolated perfused organs in field of the biomedical research compared to cell cultures either human- or animal-derived. For applying the perfusion technique (arterial affluate - venous effluate) the various organs were derived from animals (slaughter house / laboratory animals). Their results and observations have predictive value for the in-vivo situation of human beings and animals as well. It is the distinctive advantage of the use of isolated perfused organs that studies are performed in an intact organ, with physiological cell-to-cell contacts and native intracellular matrix (Uhlig, S., Methods in Pulmonary Research; 1998; ECVAM-Workshop XIII, Methods for Assessing Percutaneous Absorption; 1994). Unlike experiments with cell cultures or homogenates physiological parameters can be determined due to unimpaired structural relationships within the tissue. For example isolated lung cells or even lung slices do not show endotoxin-induced release of thromboxane which occurs in pulmonary tissue in-vivo and in perfused lung tissue under in-vitro conditions. Similarly cultured skin equivalents do not build up the complete physiology of the skin barrier system. Additionally in case of absorption they do not reflect the epidermal-dermal interactions including the part contributed by the fibro-vascular compartment comparable to the in-vivo situation. Fig. 2  While in-vivo experiments may provide good evidence that a certain substance (pure / formulated) effects the organ, only the testing in isolated organs allows an assessment of its immediate impact excluding extraorgan regulatory influences. The concentration of the substance applied to isolated organs can be very well controlled depending on the type of organ or study design. Samples of the perfusate (venous effluate) or the organ itself may be obtained easily and frequently. Unlike experiments in intact animals isolated organs allow the investigator to retain control over internal or external parameters such as type and compositions of the perfusate (nutrition) or a certain treatment before and during the experiment e.g. the impairment or improvement of the organ physiology. Perfused organs allow continuous monitoring (invasive / non-invasive methods) of many aspects of physiology and pathophysiology at the same time and under the same genetic or experimental conditions which is often not possible in laboratory animals for ethical or technical reasons. In addition isolated organs offer the opportunity of investigating administration of multiple agents by different routes and order as well as in different physical forms. The principle limitation imposed by perfused isolated organs is the duration of the study, since the tissue of the organs deteriorate with time in one or other way. The progressive decline of physiological or pathophysiological processes can be retarded by additional manipulations related to the organ but even then it can not be stopped completely. Usually the specific metabolism and morphology can be maintained for eight up to ten hours depending on the experimental set-up. Beside the different kind of perfusate (with or without erythrocytes / leucocytes, xenoperfusion) another limitation is the fact that isolated organs are deprived of nervous regulation and lymph drainage, the effects of which are largely unknown for various organs. The isolated perfused organ model provides a wealth of new opportunities to study specific organ functions. Therefore organ perfusion techniques can be performed in many biomedical areas in full accordance with the efforts of animal welfare. Table 2 demonstrates the biomedical areas (in alphabetical order) to which the authors of the proceedings apply the models presented. Table2
¶ Original: IFSCC magazine, vol. 3, no 2 / 2000; reproduced with friendly permission of Verlag für chemische Industrie H. Ziolkowsky GmbH, D-86015 Augsburg, Germany top Back to Abstracts |
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| August 6, 2000 | Copyright
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