Document Detail

Synergistic septicemic action of the gram-positive bacterial cell wall components peptidoglycan and lipoteichoic acid in the pig in vivo.
MedLine Citation:
PMID:  10774619     Owner:  NLM     Status:  MEDLINE    
Despite the fact that gram-positive infections constitute around 50% of all cases leading to septic shock, little is yet known about the mechanisms involved. This study was carried out to find out more about the effects of cell wall components peptidoglycan (PepG) and lipoteichoic acid (LTA) of the gram-positive bacterium Streptococcus pyogenes in the pig. Specific pathogen-free pigs (20 kg bodyweight) were pretreated with metyrapone (a cortisol-synthesis inhibitor) and then were given 2-h infusions of 160 microg/kg of PepG (n = 5), 160 microg/kg LTA (n=5), or a combination of both (LTA + PepG, 160 microg/kg each, n = 5). Four hours after start of the infusions, the PepG, LTA, and LTA + PepG groups showed decreases in mean arterial pressure (change of -11%, -25%, and -47% from baseline, respectively), dynamic lung compliance (-18%, -24%, and -38%), arterial oxygen tension (-10%, -16%, and -37%), changes in blood leukocyte numbers (+11%, -27%, and -67%), and increases in pulmonary vascular resistance index (+7%, +106%, and +307% from baseline) and metabolic acidosis (base excess values decreased with 1.8, 2.3 and 8.1 units). The differences between the PepG and LTA + PepG groups were statistically significant (P < 0.05, Kruskal-Wallis tests), but not between LTA and LTA + PepG groups. However, no changes in systemic nitric oxide (NO) production could be detected, which is much in contrast to studies on lower order animals. Moreover, comparison of the results obtained using this model with those obtained in a model of endotoxin-induced septic shock showed distinct difference in the mechanisms by which gram-positive and gram-negative bacterial components exert their actions. For example, a marked fall in systemic blood pressure and dynamic lung compliance is seen in both models, but in the present gram-positive sepsis model, much less interleukin-8 and tumor necrosis factor-alpha are produced. In conclusion, this study showed that PepG and LTA act synergistically to cause respiratory failure and septic shock in the pig. The infusion of the combination of PepG and LTA in the pig could serve as a new, well-controlled model for studies of gram-positive sepsis.
R J Middelveld; K Alving
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  13     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2000  
Date Detail:
Created Date:  2000-06-08     Completed Date:  2000-06-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  297-306     Citation Subset:  IM    
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Drug Synergism
Endothelin-1 / blood
Endotoxins / toxicity
Hydrocortisone / blood
Interleukin-8 / blood
Leukocyte Count
Lipopolysaccharides / toxicity*
Lung Compliance / drug effects
Metyrapone / pharmacology
Nitric Oxide / analysis
Oxygen / blood
Peptidoglycan / toxicity*
Pulmonary Circulation / drug effects
Sepsis / blood,  physiopathology*
Shock, Septic / physiopathology
Specific Pathogen-Free Organisms
Streptococcus pyogenes*
Teichoic Acids / toxicity*
Tumor Necrosis Factor-alpha / analysis
Vascular Resistance / drug effects
Reg. No./Substance:
0/Endothelin-1; 0/Endotoxins; 0/Interleukin-8; 0/Lipopolysaccharides; 0/Peptidoglycan; 0/Teichoic Acids; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 50-23-7/Hydrocortisone; 54-36-4/Metyrapone; 56411-57-5/lipoteichoic acid; 7782-44-7/Oxygen

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

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