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Macromolecular leak from extrasplenic lymphatics during endotoxemia.

Abstract：

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.

journal_name

Lymphat Res Biol

journal_title

Lymphatic research and biology

authors

Brookes ZL,Mansart A,McGown CC,Ross JJ,Reilly CS,Brown NJ

doi

10.1089/lrb.2008.1019

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

131-7

issue

eissn

1539-6851

issn

1557-8585

journal_volume

pub_type

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Macromolecular leak from extrasplenic lymphatics during endotoxemia.