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      Effect of Acute, Slightly Increased Intra-Abdominal Pressure on Intestinal Permeability and Oxidative Stress in a Rat Model

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          Abstract

          Introduction

          Intra-abdominal hypertension (IAH) is known as a common, serious complication in critically ill patients. Bacterial translocation and permeability changes are considered the pathophysiological bases for IAH-induced enterogenic endotoxemia and subsequent multiorgan failure. Nevertheless, the effects of slightly elevated intra-abdominal pressures (IAPs) on the intestinal mucosa and the associated mechanisms remain unclear.

          Methods

          To investigate the acute effects of different nitrogen pneumoperitoneum grades on colonic mucosa, male Sprague-Dawley rats were assigned to six groups with different IAPs (0 [control], 4, 8, 12, 16, and 20 mmHg, n = 6/group). During 90 min of exposure, we dynamically monitored the heart rate and noninvasive hemodynamic parameters. After gradual decompression, arterial blood gas analyses were conducted. Thereafter, structural injuries to the colonic mucosa were identified using light microscopy. Colon permeability was determined using the expression of tight junction proteins, combined with fluorescein isothiocyanate dextran (FD-4) absorption. The pro-oxidant-antioxidant balance was determined based on the levels of malondialdehyde (MDA) and antioxidant enzymes.

          Results

          IAH significantly affected the histological scores of the colonic mucosa, tight junction protein expression, mucosal permeability, and pro-oxidant-antioxidant balance. Interestingly, elevations of IAP that were lower than the threshold for IAH also showed a similar, undesirable effect. In the 8 mmHg group, mild hyponatremia, hypocalcemia, and hypoxemia occurred, accompanied by reduced blood and abdominal perfusion pressures. Mild microscopic inflammatory infiltration and increased MDA levels were also detected. Moreover, an 8-mm Hg IAP markedly inhibited the expression of tight junction proteins, although no significant differences in FD-4 permeability were observed between the 0- and 8-mmHg groups.

          Conclusions

          Acute exposure to slightly elevated IAP may result in adverse effects on intestinal permeability and the pro-oxidant-antioxidant balance. Therefore, in patients with critical illnesses, IAP should be dynamically monitored and corrected, as soon as possible, to prevent intestinal mucosal injury and subsequent gut-derived sepsis.

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          Most cited references42

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          Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. II. Recommendations.

          Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill over the past decade. In the absence of consensus definitions and treatment guidelines the diagnosis and management of IAH and ACS remains variable from institution to institution. An international consensus group of multidisciplinary critical care specialists convened at the second World Congress on Abdominal Compartment Syndrome to develop practice guidelines for the diagnosis, management, and prevention of IAH and ACS. Prior to the conference the authors developed a blueprint for consensus definitions and treatment guidelines which were refined both during and after the conference. The present article is the second installment of the final report from the 2004 International ACS Consensus Definitions Conference and is endorsed by the World Society of the Abdominal Compartment Syndrome. The prevalence and etiological factors for IAH and ACS are reviewed. Evidence-based medicine treatment guidelines are presented to facilitate the diagnosis and management of IAH and ACS. Recommendations to guide future studies are proposed. These definitions, guidelines, and recommendations, based upon current best evidence and expert opinion are proposed to assist clinicians in the management of IAH and ACS as well as serve as a reference for future clinical and basic science research.
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            Intestinal crosstalk: a new paradigm for understanding the gut as the "motor" of critical illness.

            For more than 20 years, the gut has been hypothesized to be the "motor" of multiple organ dysfunction syndrome. As critical care research has evolved, there have been multiple mechanisms by which the gastrointestinal tract has been proposed to drive systemic inflammation. Many of these disparate mechanisms have proved to be important in the origin and propagation of critical illness. However, this has led to an unusual situation where investigators describing the gut as a "motor" revving the systemic inflammatory response syndrome are frequently describing wholly different processes to support their claim (i.e., increased apoptosis, altered tight junctions, translocation, cytokine production, crosstalk with commensal bacteria, etc). The purpose of this review is to present a unifying theory as to how the gut drives critical illness. Although the gastrointestinal tract is frequently described simply as "the gut," it is actually made up of (1) an epithelium; (2) a diverse and robust immune arm, which contains most of the immune cells in the body; and (3) the commensal bacteria, which contain more cells than are present in the entire host organism. We propose that the intestinal epithelium, the intestinal immune system, and the intestine's endogenous bacteria all play vital roles driving multiple organ dysfunction syndrome, and the complex crosstalk between these three interrelated portions of the gastrointestinal tract is what cumulatively makes the gut a "motor" of critical illness.
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              The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion.

              Tissue injury at reperfusion has been reported after partial ischemia. However, previous attempts to demonstrate a component of injury caused by reperfusion after total ischemia have failed. This study was performed to evaluate the hypothesis that in such situations the extent of the tissue injury caused by ischemia itself prevented detection of a reperfusion component. Rats were subjected to near-total intestinal ischemia by means of a hydrostatic pressure clamp that produced preferential venous occlusion (strangulation) for periods from 1 to 90 minutes. Tissue injury was evaluated microscopically by a blinded examiner. Ischemic periods of 20 minutes or less did not induce detectable tissue injury. Longer durations of ischemia caused villous injury: the longer the period of ischemia, the more extensive the tissue injury. However, there was no exacerbation of injury seen after reperfusion, regardless of the duration of ischemia. In a separate series of rats, total arterial occlusion was employed without concomitant venous congestion. Such isolation arterial occlusion of 40 to 60 minutes' duration was followed by a statistically significant exacerbation of tissue injury at reperfusion. Thus total intestinal ischemia may be followed by reperfusion injury if there is no concomitant congestion and if ischemic injury is not too extensive.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                8 October 2014
                : 9
                : 10
                : e109350
                Affiliations
                [1 ]Department of Intensive Care Unit, Peking University Third Hospital, Haidian District, Beijing, P.R. China
                [2 ]Laboratory Animal Center, Peking University Health Science Center, Haidian District, Beijing, P.R. China
                [3 ]Department of Central Laboratory, Peking University Third Hospital, Haidian District, Beijing, P.R. China
                [4 ]Department of Gastroenterology, Peking University Third Hospital, Haidian District, Beijing, P.R. China
                INSERM, France
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: YXL GQY. Performed the experiments: KZ JF MY QGG LC LZ. Analyzed the data: YXL QGG. Contributed reagents/materials/analysis tools: YXL KZ JF LZ. Wrote the paper: YXL GQY.

                Article
                PONE-D-14-18007
                10.1371/journal.pone.0109350
                4190173
                25295715
                6a81dc05-d89d-42b2-a7a8-ce78c443d6f2
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 May 2014
                : 10 September 2014
                Page count
                Pages: 10
                Funding
                The work was supported by the following: Peking University - Tsinghua University Joint Center for Life Sciences and Beijing science and technology plan - Z141107002514020. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Oxidative Damage
                Cell Biology
                Oxidative Stress
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Health Care
                Gastrointestinal Critical Care
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.

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                Uncategorized

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