| Macromolecular leak from extrasplenic lymphatics during endotoxemia. | |
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MedLine Citation:
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PMID: 19778200 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The spleen has an important physiological role in maintaining blood volume; this study aimed to determine whether during pathophysiological circumstances, namely endotoxemia, the extrasplenic pathway is dysfunctional. We hypothesize that increased 'leakiness' of lymphatics in response to lipopolysaccharide (LPS) provides a route for loss of protein-rich fluid into third spaces and prevents the spleen from maintaining blood volume homeostasis. METHODS AND RESULTS: Male Wistar rats (200-280 g, n = 24) were anesthetized with thiopental (40-90 mg x kg(-1) x hr(-1), i.v.) to study the extrasplenic (vessels in mesentery adjoining the spleen) and ileal mesenteric microcirculation using fluorescently labeled albumin (66 KDa FITC-BSA, 0.02 g.100 g(-1), i.v.) with intravital microscopy. LPS (150 microg x kg(-1) x hr(-1) i.v.) induced constriction of rat extrasplenic venules (-14 +/- 2.4% from 40.4 +/- 7.8 microm, p < 0.05) and no change in arteriolar diameter (-4.6 +/- 4.7% from 32.6 +/- 4.3 microm). As the spleen is freely permeable to protein, a greater increase in venular versus arteriolar extrasplenic resistance increases intrasplenic capillary hydrostatic pressure, leading to fluid efflux into the lymphatics, draining the spleen. In agreement we report here increased extrasplenic venular resistance with LPS and lymphatic dilation to accommodate this fluid (13.5 +/- 6% from 18.5 +/- 4.8 microm, p < 0.05). However, the extrasplenic pathway then appeared to dysfunction, with macromolecular leak from extrasplenic venules (24.6 +/- 6.4%, p < 0.05) and lymphatics (12.1 +/- 3.4%, p < 0.05), indicated by increased interstitial FITC-BSA fluorescence. This was less than from ileal mesenteric venules (324 +/- 32%, p < 0.05). There was a concurrent decrease in mean arterial pressure (T(180): -15.1 +/- 6.9% from MAP of 130.3 +/- 8.8 mmHg at T(0), p < 0.05). CONCLUSION: Lymphatics are generally considered to demonstrate unidirectional and inward uptake of large molecules. However, during endotoxemia, we have demonstrated that extrasplenic lymphatics also allow the leakage of large protein molecules out into interstitial spaces. Fluid losses from extrasplenic lymphatics could therefore contribute to hypovolemia and hypotension associated with sepsis. |
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Authors:
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Zo?? L S Brookes; Arnaud Mansart; Caroline C McGown; Jonathan J Ross; Charles S Reilly; Nicola J Brown |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Lymphatic research and biology Volume: 7 ISSN: 1557-8585 ISO Abbreviation: Lymphat Res Biol Publication Date: 2009 |
Date Detail:
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Created Date: 2009-09-25 Completed Date: 2010-01-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101163587 Medline TA: Lymphat Res Biol Country: United States |
Other Details:
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Languages: eng Pagination: 131-7 Citation Subset: IM |
Affiliation:
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Academic Unit of Anaesthesia, University of Sheffield , Faculty of Medicine, Dentistry, and Health Sciences, Sheffield, United Kingdom. zoe.brookes@sheffield.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure Endotoxemia / physiopathology* Fluorescent Dyes / pharmacology Homeostasis Lipopolysaccharides / chemistry* Lymphatic Vessels / physiopathology* Male Microcirculation Proteins / chemistry Rats Rats, Wistar Sepsis / physiopathology Spleen / metabolism, physiology Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Fluorescent Dyes; 0/Lipopolysaccharides; 0/Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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