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  Vol. 123 No. 12, December 1988 TABLE OF CONTENTS
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  PAPERS READ BEFORE THE EIGHTH ANNUAL MEETING OF THE SURGICAL INFECTION SOCIETY, SAN FRANCISCO, MAY 5 TO MAY 6, 1988-Part II
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A Single Dose of Endotoxin Increases Intestinal Permeability in Healthy Humans

Sarah T. O'Dwyer, FRCS; Hamish R. Michie, FRCS; Thomas R. Ziegler, MD; Arthur Revhaug, MD; Robert J. Smith, MD; Douglas W. Wilmore, MD

Arch Surg. 1988;123(12):1459-1464.


Abstract

• To investigate the effects of endotoxin on gut barrier function, we performed paired studies of intestinal permeability in healthy humans (N=12) receiving intravenous Escherichia coli endotoxin (4 ng/kg) or 0.9% saline solution. Two nonmetabolizable sugars, lactulose and mannitol, which are standard permeability markers, were administered orally, 30 minutes before and 120 minutes after the test injection. The 12-hour urinary excretion of these substances after endotoxin/saline solution administration was used to quantitate intestinal permeability. After endotoxin administration systemic absorption and excretion of lactulose increased almost two-fold (mean±SEM, 263±36 µmol per 12 hours vs 145±19 µmol per 12 hours during saline studies). Similar but less marked alterations in mannitol absorption and excretion occurred after endotoxin injection (5.7 ± 0.3 mmol per 12 hours vs 4.9±0.3 mmol per 12 hours). When individual 12-hour lactulose excretion after endotoxin administration was related to the magnitude of systemic responses, a significant relationship occurred between lactulose excretion and elaboration of norepinephrine and between lactulose excretion and minimum white blood cell count. These data suggest that a brief exposure to circulating endotoxin increases the permeability of the normal gut. These observations are consistent with the hypothesis that during critical illness, prolonged or repeated exposure to systemic endotoxins or associated cytokines may significantly compromise the integrity of the gastrointestinal mucosal barrier.

(Arch Surg 1988;123:1459-1464)



Author Affiliations

From the Laboratory for Surgical Metabolism and Nutrition, Brigham and Women's Hospital and Harvard Medical School (Drs O'Dwyer, Michie, Ziegler, Revhaug, and Wilmore), and Joslin Diabetes Center, Harvard Medical School (Dr Smith), Boston.


Footnotes

Accepted for publication July 18, 1988.

Read before the Eighth Annual Meeting of the Surgical Infection Society, San Francisco, May 5, 1988.

Reprint requests to Surgical Metabolism Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 (Dr Wilmore).



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