ArticleGut1998
The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock.
Article in Gut, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 50 citations in OpenAlex.
- C-terminal proendothelin-1 (CT-proET-1) is associated with organ failure and predicts mortality in critically ill patients.Journal of intensive care · 2017Article
- Endotoxemia Induces IκBβ/NF-κB-Dependent Endothelin-1 Expression in Hepatic Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Endothelin-1 and its role in the pathogenesis of infectious diseases.Life sciences · 2014Review
- Repeated measurements of endothelin-1 precursor peptides predict the outcome in community-acquired pneumonia.Intensive care medicine · 2011Article
- Endothelin receptor A antagonism attenuates renal medullary blood flow impairment in endotoxemic pigs.PloS one · 2011Article
- Endothelin-1 precursor peptides correlate with severity of disease and outcome in patients with community acquired pneumonia.BMC infectious diseases · 2008Article
- Molecular mechanism of mast cell mediated innate defense against endothelin and snake venom sarafotoxin.The Journal of experimental medicine · 2007Article
- Impact of dopamine and endothelin-1 antagonism on portal venous blood flow during laparoscopic surgery.Surgical endoscopy · 2002Article
- Effects of the novel selective endothelin ET(A) receptor antagonist, SB 234551, on the cardiovascular responses to endotoxaemia in conscious rats.British journal of pharmacology · 2001Article
- Microvascular effects of oral interleukin-6 on ischemia/reperfusion in the murine small intestine.The American journal of pathology · 2000Article
- The endothelin antagonist bosentan does not improve survival in severe experimental pancreatitis in rats.International journal of pancreatology : official journal of the International Association of Pancreatology · 1999Article
- Differentiated effects on splanchnic homeostasis by selective and non-selective endothelin receptor antagonism in porcine endotoxaemia.British journal of pharmacology · 1999Article
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7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelin-1, the most potent vasoconstrictor known, is produced in septic states and may be involved in the pathophysiology of the deteriorated splanchnic circulation seen in septic shock.
aimsTo elucidate the capability of bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxic shock.
methodsIn 16 anaesthetised pigs, central and regional haemodynamics were monitored by thermodilution and ultrasonic flow probes, respectively. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by bosentan administration (to eight pigs) two hours later.
resultsEndotoxin infusion reduced cardiac index and systemic oxygen delivery; bosentan restored these parameters. The reduced mean arterial blood pressure and renal blood flow remained unaffected by bosentan. The profound reduction in gut oxygen delivery in response to endotoxin was completely abolished by bosentan. Bosentan significantly improved the notably deteriorated intestinal mucosal pH and mucosal-arterial PCO2 gap. The mucosal-portal vein PCO2 gap, used to monitor the mucosa in relation to the gut as a whole (including the spleen and pancreas), was also greatly increased by endotoxaemia and significantly reversed by bosentan.
conclusionBosentan completely restored the profound endotoxin induced reductions in systemic and gut oxygen delivery with a concomitant reversal of intestinal mucosal acidosis. Results suggest that endothelin is involved in the pronounced perfusion disturbances seen in the gut in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic shock.
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