DARWIN Digitale Dissertationen German Version Strich

FU Berlin
Digitale Dissertation

Susanne Rosemann :
Increased contractility of the small intestine in acute necrotizing pancreatitis caused by the nitric oxide inhibitor l-nitro-arginine and the influence of endotoxine
Verbesserung der Kontraktilität von Dünndarmstreifen bei nekrotisierender Pankreatitis durch NO-Antagonismus und Einfluss von Endotoxin

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Abstract

Acute necrotizing pancreatitis significantly decreases the contractility of the gut. This complication of acute necrotizing pancreatitis may cause the reduced motility and the following bacterial translocation of bacteria of the gut and their components into mesenterial lymphknotes and far away organs like liver, lungs and kidneys. This is the beginning of sepsis. In the clinic this is the most crucial complication combined with a very high grade of case fatality. In this study the nitric oxide (NO) production was inhibited in order to reduce the decreased motility of the gut. Therefore the nitric oxide inhibitor l-nitro-arginine (L-NAG) was used. L-nitro-arginine is a competitive inhibitor of the nitric oxide synthase and causes a reduced pool of NO. This study shows the significant increase of contractility caused by L-NAG in the control group as well as in the acute necrotizing pancreatitis group. This effect was only noticed during a short period of time. For the clinic this is a very important result because of the possible therapy concept. But l-nitro-arginine is not a proper inhibitor because of the nitric oxide antagonism and the muscarinerge antagonism. L-NAG increases the contractility for a short period of time followed by a decreased motility. Further this study shows that lipopolysaccharide does not additively reduce contractility neither in the control group nor in the group with acute necrotizing pancreatitis. This result shows that endotoxine consequently is no mediator of the nitric oxide system. In addiction this study shows that l-nitro-arginine has the same effect of increased contractility in both groups with endotoxine. This increase was only noticed for a short period of time like in the groups without endotoxine. It is not quite sure if this effect is dependent on the endotoxine dose. The effect of l-nitro-arginine cannot be influenced by endotoxine. Because of the combined inhibition of NO-synthase and the muscarinerge antagonism L-NAG is not a proper therapy for reduced contractility in acute necrotizing pancreatitis. For the improvement of this effect there would be a need for further examinations of other NO-synthase inhibitors.

Table of Contents

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0 Titelblatt und Inhaltsverzeichnis

1 Einleitung - Zielsetzung der Untersuchung 11

1.1 Sepsis 11

1.1.1 Definition 11

1.1.2 Bakterielle Translokation als Ursache der Sepsis 13

1.1.3 Intestinale Mechanismen der bakteriellen Translokation 14

1.2 Charakterisierung der Substanzen 16

1.2.1 Carbachol 16

1.2.2 Stickstoffmonoxid - NO-Antagonismus 17

1.2.3 l-Nitro-Arginin - L-NAG 19

1.2.4 Lipopolysaccharide (LPS) - Endotoxin 20

1.3 Zielsetzung der Untersuchung 23

1.4 Fragestellung der vorgelegten Untersuchung 24

2 Material und Methoden 25

2.1 Material 25

2.1.1 Messplatz 25

2.1.2 Verwendete Pharmaka 25

2.1.3 Organbad 26

2.1.4 Versuchstiere 27

2.2 Methoden 27

2.2.1 Induktion der ANP 27

2.2.2 Praeparation der Ileumsegmente 30

2.2.3 Messapparatur 31

2.2.4 Versuchsdurchfuehrung 32

2.2.5 Auswertmethode der Kurven 33

2.2.6 Beurteilung der Gewebeproben 34

2.2.7 Statistische Analyse 34

3 Ergebnisse 37

3.1 Effekt der nekrotisierenden Pankreatitis (ANP) und von LPS bei den Carbachol-induzierten Kontraktionen 37

3.1.1 Vergleich nekrotisierende Pankreatitis (ANP) gegen Kontrolle 37

3.1.2 Vergleich nekrotisierende Pankreatitis + LPS (ANP) gegen Kontrolle + LPS 38

3.1.3 Vergleich Kontrolle gegen Kontrolle + LPS 40

3.1.4 Vergleich ANP gegen ANP + LPS 41

3.2 Effekt von l-Nitro-Arginin 42

3.2.1 Kontrolltiere 42

3.2.2 ANP-Tiere 44

3.2.3 Kontrolltiere + Endotoxin 46

3.2.4 ANP-Tiere + Endotoxin 48

3.3 Bewertung der Gewebeproben 50

4 Diskussion 53

4.1 Methodik 53

4.2 Versuchsprotokoll 54

4.3 Kontraktilitaetsreduktion bei akut-nekrotisierender Pankreatitis 55

4.4 Wirkung des NO-Antagonisten l-Nitro-Arginin 56

4.5 Kontraktilitaetsveraenderungen durch Endotoxin 57

4.6 Wirkung des l-Nitro-Arginin nach Endotoxin-Behandlung 59

4.7 Schlussfolgerung 60

5 Zusammenfassung 63

6 Literaturverzeichnis 67

More Information:

Online available: http://www.diss.fu-berlin.de/2002/51/indexe.html
Language of PhDThesis: german
Keywords: Contractility , Bacterial translocation , Nitric oxide , L-nitro-arginine , Endotoxine
DNB-Sachgruppe: 33 Medizin
Date of disputation: 29-Jan-2002
PhDThesis from: Fachbereich Humanmedizin, Freie Universität Berlin
First Referee: Prof. Dr. med. Norbert Runkel
Second Referee: Prof. Dr. med. Axel Radlach Pries
Contact (Author): axel.rosemann@fh-bielefeld.de
Contact (Advisor): avc@klinikumvs.de
Date created:15-Apr-2002
Date available:18-Apr-2002

 

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