Document Detail


Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.
MedLine Citation:
PMID:  11736680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cardiac dysfunction during septic shock is well described but the underlying mechanisms still remain to be resolved. This study was conducted to elucidate the involvement of endothelin in cardiac function during endotoxin shock by the use of endothelin receptor antagonism. METHODS: Anaesthetised and haemodynamically stable landrace pigs received the nonpeptide mixed endothelin receptor antagonist bosentan, two hours after onset of endotoxaemia (n=7). Cardiopulmonary vascular changes, including cardiac index, stroke work index, coronary artery blood flow, rate of change of left ventricular pressure (dp/dt), and arterial and coronary sinus plasma levels of endothelin-1-like immunoreactivity were compared to a control group only receiving endotoxin (n=7). RESULTS: Plasma endothelin-1-like immunoreactivity increased threefold in the control group. Bosentan effectively counteracted the endotoxin induced decrease in cardiac index. This was accompanied by a significant reduction of both right and left ventricular afterload. In addition, coronary artery blood flow increased and coronary vascular resistance decreased compared to controls. Dp/dt remained unaffected by endothelin receptor antagonism. A further increase in plasma endothelin-1-like immunoreactivity was seen in response to bosentan. CONCLUSION: These results indicate that the increased endothelin production during endotoxaemia contributes to a depressed cardiac performance and that endothelin receptor antagonism may counteract this development. Possible mechanisms for the improved cardiac performance include both a reduction of afterload and enhanced coronary blood flow.
Authors:
M Wanecek; E Weitzberg; K Alving; A Rudehill; A Oldner
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta anaesthesiologica Scandinavica     Volume:  45     ISSN:  0001-5172     ISO Abbreviation:  Acta Anaesthesiol Scand     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-12-12     Completed Date:  2002-01-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370270     Medline TA:  Acta Anaesthesiol Scand     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  1262-70     Citation Subset:  IM    
Affiliation:
Department of Anaesthesiology & Intensive Care, Karolinska Hospital, Stockholm, Sweden. michael.wanecek@kirurgi.ki.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiac Output / drug effects
Coronary Circulation / drug effects
Endothelin-1 / blood
Hemodynamics / drug effects*
Pulmonary Circulation / drug effects
Receptors, Endothelin / antagonists & inhibitors*
Shock, Septic / blood,  physiopathology*
Stroke Volume / drug effects
Sulfonamides / pharmacology*
Swine
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Receptors, Endothelin; 0/Sulfonamides; 147536-97-8/bosentan

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


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