Der renale Ischämie-/Reperfusionsschaden (IRI) stellt in der Transplantationsmedizin ein grosses Problem dar. Fucoidin, ein potenter Antagonist der Selektin-vermittelten Leukozytenaggregation, verbesserte an der Rattenleber (in einer Konzentration von 360mg/l) das Ausmass der leukozytären Gewebeinfiltration in der frühen Phase nach Ischämie und Reperfusion. In einem Modell der isoliert hämoperfundierten Schweineniere sollte die Wirkung von Fucoidin auf die postischämische Organfunktion untersucht werden. Hierzu wurden 24 Versuche durchgeführt. Dem Blut der Versuchsgruppen wurde vor Beginn der Reperfusion Fucoidin in einer Konzentration von 100 mg/l zugesetzt. Es zeigte sich unter Fucoidin ein signifikanter Abfall des renalen Blutflusses (55 ( 28 vs. 143 ( 97 ml*min-1*100g-1, p / Renal postischemic reperfusion injury constitutes a significant problem after kidney transplantation. The polysaccharide fucoidin (360 mg/l) improves postischemic function in Ratliver, presumably by blocking selectin-mediated leukocyte adhesion. Twelve pairs of ischemic pig kidneys were reperfused in an ex vivo model with autologous blood with or without fucoidin (100 mg/L). Fucoidin resulted in a significant decrease of renal blood flow (55 ( 28 vs. 143 ( 97 mL*min-1*100g-1, p < 0.001) and increased vascular resistance (2.9 ( 2.8 vs. 1.1 ( 1.5 mmHg*mL-1*min-1*100g-1, p < 0.001). Compared to untreated control kidneys significantly more interstitial and intravascular leucocytes were found in fucoidin treated kidneys. Intraglomerular fibrinogen and thrombocytic aggregates were also increased significantly. Granulocytic emboli were present in afferent glomerular arteries of 10/12 fucoidin-treated kidneys and in 2/12 controls (p < 0.001). L-selectin-dependent granulocytic aggregation under shear stress in vitro was prevented by fucoidin in a dose-dependent fashion. However similar concentrations used in reperfused kidneys caused large granulocytic aggregates. The observed formation of embolizing granulocytic aggregates indicates limited effectiveness of fucoidin as an inhibitor of selectin-mediated leukocyte adhesion.
| Identifer | oai:union.ndltd.org:HUMBOLT/oai:edoc.hu-berlin.de:18452/15281 |
| Date | 09 July 2001 |
| Creators | Lippek, Frank |
| Contributors | Bührer, C., Lobeck., H., Lange, P. E. |
| Publisher | Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité |
| Source Sets | Humboldt University of Berlin |
| Language | German |
| Detected Language | English |
| Type | doctoralThesis, doc-type:doctoralThesis |
| Format | application/pdf |
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