| Mixed endothelin receptor antagonism with tezosentan improves intestinal microcirculation in endotoxemic shock. | |
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MedLine Citation:
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PMID: 18639249 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Microcirculatory dysfunction is a common feature of sepsis. The potent vasoconstrictor endothelin (ET) is released in sepsis and endotoxemia, potentially contributing to sepsis-induced microcirculatory failure. In this study we tested the hypothesis that mixed ET receptor antagonism with tezosentan would improve splanchnic microcirculatory blood flow in acute porcine endotoxemia. MATERIALS AND METHODS: Sixteen anesthetized and mechanically ventilated pigs received an infusion of endotoxin for 300 min. After 120 min eight pigs received a bolus dose of tezosentan 1 mg/kg followed by an infusion of tezosentan of 1 mg/kg/h throughout the experiment. Eight pigs served as endotoxin controls. Laser Doppler flowmetry was used to measure microcirculatory blood flow in the liver and in the ileal and colon mucosa. PCO(2) in the ileal mucosa was measured by air tonometry and portal vein flow by an ultrasonic flow probe. RESULTS: Endotoxin administration induced a state of shock with impaired splanchnic microcirculatory blood flow. Microcirculation in the mucosa of the colon and ileum and mucosal-arterial PCO(2) gap were improved by tezosentan. Portal vein flow was increased, but hepatic microcirculatory blood flow was not significantly improved. Tezosentan preserved cardiac index and decreased pulmonary capillary wedge pressure compared to controls, without causing any differences in the heart rate or mean arterial blood pressure response. Tezosentan also distinctly improved pH and arterial lactate values. CONCLUSIONS: The findings of this study indicate that ET is involved in the microcirculatory dysfunction seen in the ileal and colon mucosa in early endotoxemia. Moreover, this detrimental effect was counteracted by i.v. administration of the mixed ET receptor antagonist tezosentan. |
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Authors:
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Andreas Andersson; Johan Fenhammar; Robert Frithiof; Eddie Weitzberg; Alf Sollevi; Hans Hjelmqvist |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-01-11 |
Journal Detail:
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Title: The Journal of surgical research Volume: 149 ISSN: 1095-8673 ISO Abbreviation: J. Surg. Res. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-08-18 Completed Date: 2008-09-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376340 Medline TA: J Surg Res Country: United States |
Other Details:
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Languages: eng Pagination: 138-47 Citation Subset: IM |
Affiliation:
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Department of Anaesthesiology & 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 Female Intestinal Diseases / etiology Intestines / blood supply* Laser-Doppler Flowmetry Microcirculation / drug effects* Pyridines / administration & dosage* Receptors, Endothelin / antagonists & inhibitors* Shock, Septic / complications* Splanchnic Circulation / drug effects Swine Tetrazoles / administration & dosage* Vascular Diseases / drug therapy*, etiology Vasodilator Agents / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/Pyridines; 0/Receptors, Endothelin; 0/Tetrazoles; 0/Vasodilator Agents; 0/tezosentan |
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