| Endothelin-mediated gut microcirculatory dysfunction during porcine endotoxaemia. | |
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MedLine Citation:
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PMID: 20710019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The potent vasoconstrictor endothelin-1 has been implicated in the pathogenesis of the microcirculatory dysfunction seen in sepsis. The mixed endothelin receptor antagonist tezosentan and the selective endothelin A-receptor antagonist TBC3711 were used to investigate the importance of the different endothelin receptors in modulating splanchnic regional blood flow and microvascular blood flow in endotoxaemia. METHODS: Eighteen anaesthetized pigs were i.v. infused with endotoxin (Escherichia coli lipopolysaccharide, serotype 0111:b4) for 300 min. After 120 min, six animals received tezosentan and six animals received TBC3711. Six animals served as endotoxin-treated controls. Laser Doppler flowmetry was used to measure microcirculatory blood flow in the liver and ileum. Superior mesenteric artery flow (SMA(FI)) and portal vein flow (PV(FI)) were measured with ultrasonic flow probes, and air tonometry was used to measure Pco₂ in the ileal mucosa. RESULTS: TBC3711 did not improve splanchnic regional blood flow or splanchnic microvascular blood flow compared with endotoxin-treated controls. Tezosentan increased PV(FI) (P<0.05), but SMA(FI) was not improved compared with the other groups. In the tezosentan group, microvascular blood flow in the ileal mucosa (MCQ(muc)) improved and mucosal-arterial Pco₂ gap decreased (P<0.05 for both) compared with endotoxin-treated controls and the TBC3711 group. CONCLUSIONS: Tezosentan improved MCQ(muc) without any concomitant increase in SMA(FI), implying a direct positive effect on the microcirculation. TBC3711 was not effective in improving regional splanchnic blood flow or splanchnic microvascular blood flow. Dual endothelin receptor antagonism was necessary to improve MCQ(muc), indicating a role for the endothelin B-receptor in mediating the microcirculatory failure in the ileal mucosa. |
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Authors:
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A Andersson; J Fenhammar; E Weitzberg; A Sollevi; H Hjelmqvist; R Frithiof |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-14 |
Journal Detail:
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Title: British journal of anaesthesia Volume: 105 ISSN: 1471-6771 ISO Abbreviation: Br J Anaesth Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2010-11-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372541 Medline TA: Br J Anaesth Country: England |
Other Details:
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Languages: eng Pagination: 640-7 Citation Subset: IM |
Affiliation:
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Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden. andreas.andersson@karolinska.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Endothelin-1 / physiology* Endotoxemia / complications, physiopathology* Female Hypertension, Pulmonary / etiology, prevention & control Ileum / blood supply Intestinal Mucosa / blood supply Isoxazoles / pharmacology Microcirculation / drug effects, physiology Pyridines / pharmacology Receptor, Endothelin A / antagonists & inhibitors, physiology Receptor, Endothelin B / antagonists & inhibitors, physiology Splanchnic Circulation / drug effects, physiology Sulfones / pharmacology Sus scrofa Tetrazoles / pharmacology Vasodilator Agents / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1; 0/Isoxazoles; 0/N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide; 0/Pyridines; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 0/Sulfones; 0/Tetrazoles; 0/Vasodilator Agents; 0/tezosentan |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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