Document Detail


Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia.
MedLine Citation:
PMID:  12785007     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heme oxygenase (HO) has both deleterious and protective effects in various shock models. Most of these data have been derived from experiments with hypodynamic shock states associated with depressed cardiac output. Therefore we studied the role of HO during long-term porcine hyperdynamic endotoxemia characterized by a sustained increase in cardiac output resulting from colloid resuscitation to maintain mean arterial pressure > 60 mmHg. Systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of the HO-inhibitor tin-mesoporphyrin (SnMP) were assessed in anesthetized and mechanically ventilated animals. After 12 h of continuous intravenous lipopolysaccharide (LPS), animals received either vehicle (n = 6) or SnMP (n = 8; 6 micromol kg(-1) i.v. over 30 min at 12 and 18 h of LPS). Measurements were performed before LPS, before SnMP infusion, and at 24 h of LPS. SnMP did not influence systemic hemodynamics but significantly increased mean pulmonary artery pressure. Although liver blood flow was not affected, SnMP markedly impaired liver lactate clearance. HO inhibition was associated with increased plasma nitrate levels likely the result of increased NO production. Our results suggest a protective role of HO activation during hyperdynamic porcine endotoxemia possibly as a result of an interaction with the LPS-induced increase in NO formation.
Authors:
Marek Nalos; Damian Vassilev; Antje Pittner; Pierre Asfar; Uwe Bernd Brückner; Elisabeth Marion Schneider; Michael Georgieff; Peter Radermacher; Gebhard Froeba
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  19     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-04     Completed Date:  2004-02-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  526-32     Citation Subset:  IM    
Affiliation:
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Volume / drug effects
Chronic Disease
Disease Models, Animal
Endotoxemia / blood,  drug therapy*,  physiopathology
Enzyme Inhibitors / pharmacology*
Glutathione / blood
Heme Oxygenase (Decyclizing) / antagonists & inhibitors*
Hemodynamics / drug effects,  physiology
Hydrogen-Ion Concentration
Isoprostanes / blood
Lactates / metabolism
Lipopolysaccharides / toxicity*
Lung / drug effects,  physiopathology
Metalloporphyrins / pharmacology*
Oxygen Consumption / drug effects
Pulmonary Artery / drug effects,  physiopathology
Swine
Time Factors
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Isoprostanes; 0/Lactates; 0/Lipopolysaccharides; 0/Metalloporphyrins; 106344-20-1/tin mesoporphyrin; 70-18-8/Glutathione; EC 1.14.99.3/Heme Oxygenase (Decyclizing)

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


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