Document Detail


Lysozyme: a mediator of myocardial depression and adrenergic dysfunction in septic shock in dogs.
MedLine Citation:
PMID:  12676541     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objective of the present study was to identify the nature of a filterable cardiodepressant substance (FCS) that contributes to myocardial dysfunction in a canine model of Escherichia coli septic shock. In a previous study, it was found that FCS increased in plasma after 4 h of bacteremia (Am J Physiol 1993;264:H1402) in which FCS was identified by a bioassay that included a right ventricular trabecular (RVT) preparation. In that study, FCS was only partially identified by pore filtration techniques and was found to be a protein of molecular weight between 10 and 30 K. In the present study, FCS was further purified by size exclusion high-pressure liquid chromatography, until a single band was identified on one-dimensional gel electrophoresis. This band was then subjected to tandem mass spectrometry and protein-sequencing techniques and both techniques identified FCS as lysozyme c (Lzm-S), consistent with that originating from the canine spleen. Confirmatory tests showed that purified Lzm-S produced myocardial depression in the RVT preparation at concentrations achieved during sepsis in the in vivo preparation. In addition, Lzm-S inhibited the adrenergic response induced by field stimulation and the beta- agonist isoproterenol in in vitro preparations, these results suggesting that Lzm-S may inhibit the sympathetic response in sepsis. The present findings indicate that Lzm-S originating from disintegrating leukocytes from organs such as the spleen contributes to myocardial dysfunction in this model. The mechanism may relate to its binding or hydrolysis of a cardiac membrane glycoprotein thereby interfering with myocardial excitation-contraction coupling in sepsis.
Authors:
Steven N Mink; Hans Jacobs; Deepak Bose; Krika Duke; Zhao Qin Cheng; Gang Liu; R Bruce Light
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  35     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-04-04     Completed Date:  2003-12-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  265-75     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Manitoba, Manitoba R3E-0Z3, Winnipeg, Canada. minksn@cc.umanitoba.ca
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Antagonists / isolation & purification,  toxicity*
Adrenergic beta-Agonists / pharmacology
Animals
Dogs
Escherichia coli Infections / chemically induced,  etiology*,  physiopathology
Heart / physiopathology*
Isometric Contraction
Isoproterenol / pharmacology
Muramidase / isolation & purification,  toxicity*
Myocardial Contraction / drug effects
Shock, Septic / chemically induced,  etiology*,  physiopathology
Spleen / enzymology
Trisaccharides / pharmacology
Chemical
Reg. No./Substance:
0/Adrenergic Antagonists; 0/Adrenergic beta-Agonists; 0/Trisaccharides; 41708-93-4/chitotriose; 7683-59-2/Isoproterenol; EC 3.2.1.17/Muramidase

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