Document Detail


MedLine Citation:
PMID:  14707578     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Reversible myocardial depression in sepsis has been ascribed to the release of inflammatory mediators. We recently found that lysozyme c (Lzm-S), consistent with that originating from the spleen, was a mediator of myocardial depression in an Escherichia coli model of septic shock in dogs. We further showed in a right ventricular trabecular (RVT) preparation that Lzm-S's depressant activity could be blocked by N,N',N" triacetylglucosamine (TAC), a competitive inhibitor of Lzm-S. We hypothesized that Lzm-S binds to or cleaves a cardiac membrane glycoprotein, thereby interfering with myocardial contraction in sepsis. In the present study, we examined whether TAC could prevent myocardial depression in an in vivo preparation and whether other related N-acetylglucosamine (NAG) structures could also inhibit Lzm-S's effect in RVT. DESIGN: Randomized experimental study. SETTING: University laboratory. SUBJECTS: Anesthetized, mechanically ventilated dogs. INTERVENTIONS: We produced sepsis by infusion of E. coli over an approximately 6-hr period. MEASUREMENTS AND MAIN RESULTS: We examined the effect of TAC on stroke work, our primary index of myocardial function, when treatment was administered before sepsis (pretreatment) and after 1.5 hrs (early treatment study) and 3.5 hrs of sepsis (late treatment study; LTS). In the pretreatment study and early treatment study, myocardial depression would have not yet occurred but would have already been present in the late treatment study. In RVT, we assessed the effect of other NAG oligosaccharides and variants to the NAG structure on Lzm-S's depressant activity. In pretreatment and the early treatment study, TAC prevented the reduction in stroke work observed in nontreated septic groups but did not reverse the reduction found in the late treatment study. In RVT, of the compounds tested, only N,N'-diacetylglucosamine showed an inhibitory effect. CONCLUSIONS: We found that TAC, a competitive inhibitor of Lzm-S, prevented myocardial depression in experimental sepsis. Only specific NAG structures are inhibitory to Lzm-S's depressant activity. TAC may be useful in attenuating cardiovascular collapse in sepsis.
Authors:
Steven N Mink; Hans Jacobs; Krika Duke; Deepak Bose; Zhao-Qin Cheng; R Bruce Light
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  32     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-06     Completed Date:  2004-02-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  184-93     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg. minksn@cc.umanitoba.ca
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MeSH Terms
Descriptor/Qualifier:
Acetylglucosaminidase / pharmacology*
Animals
Cardiac Output / drug effects*
Disease Models, Animal
Dogs
Escherichia coli Infections / drug therapy*
Female
Male
Muramidase / drug effects,  metabolism*
Myocardial Contraction / drug effects
Myocardial Depressant Factor / analysis
Probability
Random Allocation
Reference Values
Sensitivity and Specificity
Shock, Septic / drug therapy*
Stroke Volume / drug effects
Ventricular Dysfunction, Left / prevention & control*
Chemical
Reg. No./Substance:
0/Myocardial Depressant Factor; EC 3.2.1.17/Muramidase; EC 3.2.1.52/Acetylglucosaminidase
Comments/Corrections
Comment In:
Crit Care Med. 2004 Jan;32(1):304-5   [PMID:  14707605 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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