Document Detail

Macromolecular leak from extrasplenic lymphatics during endotoxemia.
MedLine Citation:
PMID:  19778200     Owner:  NLM     Status:  MEDLINE    
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.
Zo?? L S Brookes; Arnaud Mansart; Caroline C McGown; Jonathan J Ross; Charles S Reilly; Nicola J Brown
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Lymphatic research and biology     Volume:  7     ISSN:  1557-8585     ISO Abbreviation:  Lymphat Res Biol     Publication Date:  2009  
Date Detail:
Created Date:  2009-09-25     Completed Date:  2010-01-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101163587     Medline TA:  Lymphat Res Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  131-7     Citation Subset:  IM    
Academic Unit of Anaesthesia, University of Sheffield , Faculty of Medicine, Dentistry, and Health Sciences, Sheffield, United Kingdom.
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MeSH Terms
Blood Pressure
Endotoxemia / physiopathology*
Fluorescent Dyes / pharmacology
Lipopolysaccharides / chemistry*
Lymphatic Vessels / physiopathology*
Proteins / chemistry
Rats, Wistar
Sepsis / physiopathology
Spleen / metabolism,  physiology
Time Factors
Reg. No./Substance:
0/Fluorescent Dyes; 0/Lipopolysaccharides; 0/Proteins

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