Document Detail

N,N'-diacetylchitobiose, an inhibitor of lysozyme, reverses myocardial depression and lessens norepinephrine requirements in Escherichia coli sepsis in dogs.
MedLine Citation:
PMID:  17885642     Owner:  NLM     Status:  MEDLINE    
Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered chitobiose after 3.5 h of E. coli bacteremia and compared stroke work (SW) and MAP at 6 h with a sepsis control group. In a 12-h study, we determined whether chitobiose treatment can reduce the need for NE requirements during 12 h of bacteremia. In the latter study, either chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.
Steven N Mink; Krika Kasian; Hans Jacobs; Zhao-Qin Cheng; R Bruce Light
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  29     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-08-13     Completed Date:  2008-09-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  681-7     Citation Subset:  IM    
Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
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MeSH Terms
Bacteremia / drug therapy,  enzymology,  physiopathology
Cardiomyopathies / drug therapy*,  enzymology,  physiopathology
Disaccharides / pharmacology*
Enzyme Inhibitors / pharmacology*
Escherichia coli*
Escherichia coli Infections / drug therapy*,  enzymology,  physiopathology
Inflammation Mediators / metabolism
Muramidase / antagonists & inhibitors*
Norepinephrine / pharmacology*
Shock, Septic / drug therapy*,  enzymology,  physiopathology
Stroke Volume / drug effects
Time Factors
Vasoconstrictor Agents / pharmacology*
Reg. No./Substance:
0/Disaccharides; 0/Enzyme Inhibitors; 0/Inflammation Mediators; 0/Vasoconstrictor Agents; 2706-64-1/N,N-diacetylchitobiose; 51-41-2/Norepinephrine; EC

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