Timing and Mechanism of Sepsis-Induced Delayed Gastric Emptying in a Novel Mouse Model

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Date
2012-05-09
Authors
Samis, Andrew James Willis
Keyword
gastric emptying , sepsis
Abstract
Sepsis-induced delayed gastric emptying is a significant clinical problem for patients in intensive care units worldwide. A series of studies were carried out to examine the nature and mechanisms of sepsis-induced delayed gastric emptying using a novel mouse model which used a standard food source and was devoid of upper gastrointestinal tract trauma and restraint. Using this model, lipopolysaccharide (LPS) injection produced a dose-dependent decrease in gastric emptying which onset by one hour. LPS produced an alteration in mouse behavior and piloerection at 30 minutes, increased resting respiratory rate at 3 hours, and did not impact body temperature. The onset of sepsis-induced delayed gastric emptying was closer to those centrally-mediated clinical signs of sepsis (altered behavior and piloerection) than to the peripherally-mediated clinical signs (respiratory rate) suggesting a central mechanism. C-Fos activation of the area postrema (AP), the nucleus of the solitary tract (NTS), and the dorsal motor nucleus of the vagus (DMV) was examined 30 minutes after LPS injection which is the onset time for sepsis-induced delayed gastric emptying. LPS exposure produced significantly more activated neurons in the AP and NTS, and less in the DMV. These results may suggest a central mechanism with the AP and NTS inhibiting the DMV. Examination of isolated strips of gastric antrum in a tissue bath showed a decreased contractile response to electrical field stimulation and carbachol after injection of LPS. This occurred at 18 hours post LPS injection, but not at 6 hours. Using the mouse model, sepsis-induced delayed gastric emptying was shown to be occurring at 6 hours when no difference in contractility was measurable suggesting intrinsic changes are not the cause. These studies suggest a new mechanistic paradigm for sepsis-induced delayed gastric emptying in which there is a biphasic response. This involves an initial rapid, centrally-mediated delay in gastric emptying occurring the first hour and followed by an intrinsic tissue-level response several hours later characterized by a decrease in gastric muscle contractility.
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