Effects of acute intra-abdominal hypertension on multiple intestinal barrier functions in rats.
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ABSTRACT:
SUBMITTER: Leng Y
PROVIDER: S-EPMC4793228 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
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Project description:Background/Aims:Severe acute pancreatitis (SAP) is associated with intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS), but treatment of these conditions is difficult. We studied a rat model of SAP + IAH to determine the effect of oral administration of Clostridium butyricum and butyrate (its major metabolite) on intestinal barrier functions. Methods:A total of 48 rats were assigned to four groups, with 12 rats per group: Sham, SAP+IAH, SAP+IAH+C. butyricum, and SAP + IAH + butyrate. SAP was induced by sodium taurocholate infusion into the biliopancreatic duct, intra-abdominal pressure (IAP), mortality was measured 24 h later, and then rats were euthanized. The plasma levels of several markers [amylase, diamine oxidase (DAO), fluorescein isothiocyanate (FITC)-dextran, tumor necrosis factor alpha (TNF-?), interleukin (IL)-6, IL-1?, IL-12, lipopolysaccharide (LPS)] and fecal butyric acid level were determined. The pancreas and intestine were examined using histology, and RT-PCR and Western blotting of intestinal tissues were used to measure the expression of six markers {tight junction proteins [zonula occludens protein-1 (ZO-1), claudin-1, claudin-2, occluding], matrix metalloproteinase 9 [MMP9], and TNF-?}. The gut flora of the rats was examined by 16S rRNA sequencing. Results:Induction of SAP + IAH altered several functions of the intestinal barrier, and enhanced intestinal permeability, decreased the levels of ZO-1, claudin-1, occludin, the richness and diversity of the microflora community, the relative abundance (RA) of Firmicutes, and the number of probiotic organisms. However, induction of SAP+IAH increased the expression of claudin-2, MMP9, and TNF-?, and the RA of Proteobacteria and pathogens in the feces. Rats that received oral C. butyricum or butyrate had reduced intestinal injury and plasma levels of DAO, LPS, and inflammatory cytokines. Conclusion:This study of rats with SAP+IAH indicated that oral dosing of C. butyricum or butyrate reduced intestinal injury, possibly by altering the functions of the intestinal mucosal barrier.
| S-EPMC7658654 | biostudies-literature
Project description:IntroductionAbdominal distension is common in critical illness. There is a growing recognition that intra-abdominal hypertension (IAH) may complicate nonsurgical critical illness as well as after abdominal surgery. However, the pathophysiological basis of the injury to the intestinal mucosal barrier and its influence on the onset of abdominal compartment syndrome (ACS) and multiorgan dysfunction syndrome (MODS) remain unclear. We measured intestinal microcirculatory blood flow (MBF) during periods of raised intra-abdominal pressure (IAP) and examined how this influenced intestinal permeability, systemic endotoxin release, and histopathological changes.MethodsTo test different grades of IAH to the injury of intestinal mucosa, 96 New Zealand white rabbits aged 5 to 6 months were exposed to increased IAP under nitrogen pneumoperitoneum of 15 mmHg or 25 mmHg for 2, 4 or 6 hours. MBF was measured using a laser Doppler probe placed against the jejunal mucosa through a small laparotomy. Fluorescein isothiocyanate (FITC)-conjugated dextran was administered by gavage. Intestinal injury and permeability were measured using assays for serum FITC-dextran and endotoxin, respectively, after each increase in IAP. Structural injury to the intestinal mucosa at different levels of IAH was confirmed by light and transmission electron microscopy.ResultsMBF reduced from baseline by 40% when IAP was 15 mmHg for 2 hours. This doubled to 81% when IAP was 25 mmHg for 6 hours. Each indicator of intestinal injury increased significantly, proportionately with IAP elevation and exposure time. Baseline serum FITC-dextran was 9.30 (± SD 6.00) μg/ml, rising to 46.89 (±13.43) μg/ml after 15 mmHg IAP for 4 hours (P <0.01), and 284.59 (± 45.18) μg/ml after 25 mmHg IAP for 6 hours (P <0.01). Endotoxin levels showed the same pattern. After prolonged exposure to increased IAP, microscopy showed erosion and necrosis of jejunal villi, mitochondria swelling and discontinuous intracellular tight junctions.ConclusionsIntra-abdominal hypertension can significantly reduce MBF in the intestinal mucosa, increase intestinal permeability, result in endotoxemia, and lead to irreversible damage to the mitochondria and necrosis of the gut mucosa. The dysfunction of the intestinal mucosal barrier may be one of the important initial factors responsible for the onset of ACS and MODS.
| S-EPMC4057115 | biostudies-literature
Project description:BackgroundIntra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.MethodsIn this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization.ResultsA total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th-75th percentile: -18.7% [- 28.4 to - 4.7%] vs. - 5.4% [- 18.0% to 0], P = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (P = 0.018). Per-protocol analysis confirmed these results (P = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (all P < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups.ConclusionNeostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial. Trial registration Clinical Trial No: NCT02543658 (registered August /27, 2015).
| S-EPMC8892692 | biostudies-literature
Project description:Exposure to microgravity or weightlessness leads to various adaptive and pathophysiological alterations in digestive structures and physiology. The current study was carried out to investigate responses of intestinal mucosal barrier functions to simulated weightlessness, by using the hindlimb unloading rats model. Compared with normal controls, simulated weightlessness damaged the intestinal villi and structural integrity of tight junctions, up-regulated the expression of pro-apoptotic protein Bax while down-regulated the expression of anti-apoptotic protein Bcl-2, thus improved the intestinal permeability. It could also influence intestinal microbiota composition with the expansion of Bacteroidetes and decrease of Firmicutes. The predicted metagenomic analysis emphasized significant dysbiosis associated differences in genes involved in membrane transport, cofactors and vitamins metabolism, energy metabolism, and genetic information processing. Moreover, simulated weightlessness could modify the intestinal immune status characterized by the increase of proinflammatory cytokines, decrease of secretory immunoglobulin A, and activation of TLR4/MyD88/NF-κB signaling pathway in ileum. These results indicate the simulated weightlessness disrupts intestinal mucosal barrier functions in animal model. The data also emphasize the necessity of monitoring and regulating astronauts' intestinal health during real space flights to prevent breakdowns in intestinal homeostasis of crewmembers.
| S-EPMC6011188 | biostudies-literature
Project description:Cinnamaldehyde is an aromatic aldehyde isolated from the essential oil of cinnamon. It has been proved to possess various bioactivities such as anti-inflammation, anti-bacteria and antihypertensive. Nevertheless, early weaning could lead to intestinal stress, causing a range of intestinal health problems. The aim of this study is to explore the effects of cinnamaldehyde on gut barrier integrity, inflammatory responses, and intestinal microbiome of early weaned rats. In this study, treatment with cinnamaldehyde (100 or 200 mg/kg bodyweight/day) for 2 weeks significantly promoted the production of mucins in the colonic epithelial tissue of rats. Cinnamaldehyde supplementation significantly upregulated the expression of Muc2, TFF3 and the tight junction proteins (ZO-1, claudin-1, and occludin). Hematoxylin and eosin staining results showed that colonic histopathological changes were recovered by cinnamaldehyde supplementation. The mRNA expression of IL-6 and TNF-α were significantly decreased in the cinnamaldehyde groups while the TNF-α protein levels were significantly decreased in the two cinnamaldehyde groups. Cinnamaldehyde treatment obviously attenuated the activation of NF-κB signaling pathway in rat colonic tissue and suppressed the production of inflammatory cytokines. Furthermore, cinnamaldehyde supplementation remodeled the gut microbiome structure, at the genus level, Akkermansia, Bacteroides, Clostridium III, Psychrobacter, Intestinimonas were increased, whereas those of Ruminococcus, Escherichia/Shigella were obviously decreased in the cinnamaldehyde treated groups. These findings indicated that cinnamaldehyde could effectively enhance intestinal barrier integrity, ameliorate inflammatory responses and remodel gut microbiome in early weaned rats.
| S-EPMC8545821 | biostudies-literature
Project description:IntroductionMechanical ventilation with high positive end-expiratory pressure (PEEP) has been used in patients with acute respiratory distress syndrome (ARDS) and intra-abdominal hypertension (IAH), but the role of PEEP in minimizing lung injury remains controversial. We hypothesized that in the presence of acute lung injury (ALI) with IAH: 1) higher PEEP levels improve pulmonary morphofunction and minimize lung injury; and 2) the biological effects of higher PEEP are more effective in extrapulmonary (exp) than pulmonary (p) ALI.MethodsIn 48 adult male Wistar rats, ALIp and ALIexp were induced by Escherichia coli lipopolysaccharide intratracheally and intraperitoneally, respectively. After 24 hours, animals were anesthetized and mechanically ventilated (tidal volume of 6 mL/kg). IAH (15 mmHg) was induced and rats randomly assigned to PEEP of 5 (PEEP5), 7 (PEEP7) or 10 (PEEP10) cmH2O for 1 hour.ResultsIn both ALIp and ALIexp, higher PEEP levels improved oxygenation. PEEP10 increased alveolar hyperinflation and epithelial cell damage compared to PEEP5, independent of ALI etiology. In ALIp, PEEP7 and PEEP10 increased lung elastance compared to PEEP5 (4.3 ± 0.7 and 4.3 ± 0.9 versus 3.1 ± 0.3 cmH2O/mL, respectively, P <0.01), without changes in alveolar collapse, interleukin-6, caspase-3, type III procollagen, receptor for advanced glycation end-products, and vascular cell adhesion molecule-1 expressions. Moreover, PEEP10 increased diaphragmatic injury compared to PEEP5. In ALIexp, PEEP7 decreased lung elastance and alveolar collapse compared to PEEP5 (2.3 ± 0.5 versus 3.6 ± 0.7 cmH2O/mL, P <0.02, and 27.2 (24.7 to 36.8) versus 44.2 (39.7 to 56.9)%, P <0.05, respectively), while PEEP7 and PEEP10 increased interleukin-6 and type III procollagen expressions, as well as type II epithelial cell damage compared to PEEP5.ConclusionsIn the current models of ALI with IAH, in contrast to our primary hypothesis, higher PEEP is more effective in ALIp than ALIexp as demonstrated by the activation of biological markers. Therefore, higher PEEP should be used cautiously in the presence of IAH and ALI, mainly in ALIexp.
| S-EPMC4095606 | biostudies-literature
Project description:BackgroundIntra-abdominal hypertension is frequently present in critically ill patients and is an independent predictor for mortality. Risk factors for intra-abdominal hypertension and abdominal compartment syndrome have been widely investigated. However, data are lacking on prevalence and outcome in high-risk patients. Our objectives in this study were to investigate prevalence and outcome of intra-abdominal hypertension and abdominal compartment syndrome in high-risk patients in a prospective, observational, single-center cohort study.ResultsBetween March 2014 and March 2016, we included 503 patients, 307 males (61%) and 196 females (39%). Patients admitted to the intensive care unit with a diagnosis of pancreatitis, elective or emergency open abdominal aorta surgery, orthotopic liver transplantation, other elective or emergency major abdominal surgery and trauma were enrolled. One hundred and sixty four (33%) patients developed intra-abdominal hypertension and 18 (3.6%) patients developed abdominal compartment syndrome. Highest prevalence of abdominal compartment syndrome occurred in pancreatitis (57%) followed by orthotopic liver transplantation (7%) and abdominal aorta surgery (5%). Length of intensive care stay increased by a factor 4 in patients with intra-abdominal hypertension and a factor 9 in abdominal compartment syndrome, compared to patients with normal intra-abdominal pressure. Rate of renal replacement therapy was higher in abdominal compartment syndrome (38.9%) and intra-abdominal hypertension (8.2%) compared to patients with normal intra-abdominal pressure (1.2%). Both intensive care mortality and 90-day mortality were significantly higher in intra-abdominal hypertension (4.8% and 15.2%) and abdominal compartment syndrome (16.7% and 38.9%) compared to normal intra-abdominal pressure (1.2% and 7.1%). Body mass index (odds ratio 1.08, 95% confidence interval 1.03-1.13), mechanical ventilation at admission (OR 3.52, 95% CI 2.08-5.96) and Apache IV score (OR 1.03, 95% CI 1.02-1.04) were independent risk factors for the development of intra-abdominal hypertension or abdominal compartment syndrome.ConclusionsThe prevalence of abdominal compartment syndrome was 3.6% and the prevalence of intra-abdominal hypertension was 33% in this cohort of high-risk patients. Morbidity and mortality increased when intra-abdominal hypertension or abdominal compartment syndrome was present. The patient most at risk of IAH or ACS in this high-risk cohort has a BMI > 30 kg/m2 and was admitted to the ICU after emergency abdominal surgery or with a diagnosis of pancreatitis.
| S-EPMC7530150 | biostudies-literature
Project description:BackgroundGeneral pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear.ObjectivesThis review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS).MethodsWe performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH.ResultsWe identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality.ConclusionsCurrent evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.
| S-EPMC9502789 | biostudies-literature
Project description:BackgroundThe aim of this study was to analyse the relationship between intra-abdominal hypertension (IAH) and severity of acute pancreatitis (AP) measured by the revised Atlanta classification (RAC) and determinant-based classification (DBC). Secondary objectives were to assess IAH as a predictor of morbidity and mortality in the ICU.MethodsThis prospective international observational study included patients admitted to the ICU with AP and at least one organ failure. Information was collected on demographics, severity scores at admission using RAC and DBC, organ failure, mechanical ventilation, continuous renal replacement therapy (CRRT), surgery and mortality. Maximum intra-abdominal pressure (IAP) during ICU stay was used for analysis.ResultsSome 374 patients were included. The hospital mortality rate was 28·9 per cent. IAP was measured in 301 patients (80·5 per cent), of whom 274 (91·0 per cent) had IAH and 103 (34·2 per cent) acute compartment syndrome. A higher IAH grade was more likely in patients with severe AP (42 per cent for grade I versus 84 per cent for grade IV) and acute critical pancreatitis (9 versus 25 per cent; P = 0·001). Compared with grade I IAH, patients with grade IV had more infected necrosis (16 versus 28 per cent; P = 0·005), need for surgery (27 versus 50 per cent; P = 0·006), mechanical ventilation (53 versus 84 per cent; P = 0·007) and requirement for CRRT (22 versus 66 per cent; P < 0·001). IAH predicted shock (area under receiver operating characteristic (ROC) curve (AUC) 0·79, 95 per cent c.i. 0·73 to 0·84), respiratory failure (AUC 0·82, 0·77 to 0·87), renal failure (AUC 0·93, 0·89 to 0·96) and mortality (AUC 0·89, 0·86 to 0·93).ConclusionIAH was associated with severity of AP classified according to both RAC and DBC systems. IAP grade can predict outcome of AP during ICU stay.
| S-EPMC5989946 | biostudies-literature
Project description:There have been concerns about the potential health risks posed by microplastics (MP). The detection of MP in a variety of food products revealed that humans are ingesting MP. Nevertheless, there is a paucity of data about their impacts, as well as their uptake, on intestinal barrier integrity. This study examined the toxic effects of oral administration of two doses of polyethylene microplastics (PE-MP) (3.75 or 15 mg/kg/day for 5 weeks; mean particle size: 4.0-6.0 µm) on the intestinal barrier integrity in rats. Moreover, the effect of melatonin treatment with MP exposure was also assessed. The PE-MP particle uptake, histopathological changes, Alcian blue staining, Muc2 mRNA, proinflammatory cytokines (IL-1β and TNF-α), and cleaved caspase-3, as well as tight junction proteins (claudin-1, myosin light-chain kinase (MLCK), occludin, and zonula occludens-1 (ZO-1)) were assessed. Oral administration of PE-MP resulted in apparent jejunal histopathological alterations; significantly decreased mucin secretion, occludin, ZO-1, and claudin-1 expression; and significantly upregulated MLCK mRNA, IL-1β concentration, and cleaved caspase-3 expression. Melatonin reversed these altered parameters and improved the PE-MP-induced histopathological and ultrastructure changes. This study highlighted the PE-MP's toxic effect on intestinal barrier integrity and revealed the protective effect of melatonin.
| S-EPMC10488227 | biostudies-literature