Lysozyme: a mediator of myocardial depression and adrenergic dysfunction in septic shock in dogs.
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.
Mink
Steven N
SN
Department of Medicine, University of Manitoba, Manitoba R3E-0Z3, Winnipeg, Canada. minksn@cc.umanitoba.ca
Jacobs
Hans
H
Bose
Deepak
D
Duke
Krika
K
Cheng
Zhao Qin
ZQ
Liu
Gang
G
Light
R Bruce
RB
D018674:Adrenergic Antagonists / Q000302:isolation & purification / Q000633:toxicity*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004927:Escherichia coli Infections / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D007537:Isometric Contraction; D007545:Isoproterenol / Q000494:pharmacology; D009113:Muramidase / Q000302:isolation & purification / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects; D012772:Shock, Septic / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D013154:Spleen / Q000201:enzymology; D014312:Trisaccharides / Q000494:pharmacology
D018674:Adrenergic Antagonists; D000318:Adrenergic beta-Agonists; D014312:Trisaccharides; C041161:chitotriose; D009113:Muramidase; D007545:Isoproterenol