Inhibition of intestinal transit by resuscitation-induced gut edema is reversed by L-NIL

BACKGROUND: Post-resuscitation gut edema and associated gut dysfunction is a common and significant clinical problem that occurs after traumatic injury and shock. We have shown previously that gut edema without ischemia/reperfusion injury delays intestinal transit [1]. We hypothesized that gut edema increases expression of inducible nitric oxide synthase (iNOS) protein, and that selective iNOS inhibition using L-NIL reverses the delayed intestinal transit associated with gut edema. MATERIALS AND METHODS: One hour prior to laparotomy, rats were pretreated with 10 mg/kg body weight of intraperitoneal L-NIL or saline vehicle and underwent 80 ml/kg body weight of 0.9% saline + superior mesenteric venous pressure elevation (Edema) or sham surgery (Sham). A duodenal catheter was placed to allow injection of a fluorescent dye for the measurement of intestinal transit. At 6 h, the small bowel was divided and the mean geometric center (MGC) of fluorescent dye was measured to determine transit. Ileum was harvested for histological assessment of mucosal injury, evaluation of iNOS protein expression by Western blotting, and MPO activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Data are expressed as mean +/- SEM, n = 3-6 and * = P <0.05 using ANOVA. RESULTS: Gut edema, expressed as increased wet-to-dry ratio, was associated with decreased intestinal transit and elevated iNOS protein expression. Pretreatment with l-NIL improved intestinal transit and decreased expression of iNOS protein without decreasing intestinal tissue water compared to edema animals. There was no difference in mucosal injury or MPO activity among groups. CONCLUSION: Gut edema delays intestinal transit via an iNOS-mediated mechanism.     

肠功能障碍的营养支持

肠道是维持人体营养、生存的重要器官之一。长期以来，人们对肠功能的认识偏重于营养物质的消化、吸收。通常所谓的“肠衰竭（intestinalfailure）”是指患者丧失了小肠这一器官或小肠的功能，不能通过消化吸收来维持机体最低营养需要量、甚至水与电解质的平衡。在日常临床实践     

外科感染与肠功能障碍

肠功能障碍是重症医学研究的热点之一,肠功能在重症患者疾病发生和发展过程中发挥着重要作用.20世纪80年代就有学者提出,肠道是多器官功能障碍综合征(multiple organ dysfunction syndrome, MODS)的始动器官.专家们认为,肠道是人体内最大的储菌库和内毒素库,一旦肠黏膜完整性和屏障保护功能被破坏,肠道内的细菌或内毒素通过向肠外组织易位可引起肠道局部或全身性的不可控制的炎性反应[1].     

外科感染与肠功能障碍

肠功能障碍是重症医学研究的热点之一．肠功能在重症患者疾病发生和发展过程中发挥着重要作用。20世纪80年代就有学者提出．肠道是多器官功能障碍综合征（multiple organ dysfunction syndrome，MODS）的始动器官。     

Beneficial effects of lexipafant, a PAF antagonist on gut barrier dysfunction caused by intestinal ischemia and reperfusion in rats

BACKGROUND: Platelet-activating factor (PAF) may play a pivotal role in the pathogenesis of intestinal ischemic injury. METHODS: The potential role of PAF in intestinal ischemia and reperfusion (I/R) and the development of gut endothelial and epithelial barrier dysfunction and distant organ injury were investigated by pretreatment with a PAF antagonist, lexipafant. Bidirectional permeability of the intestinal barrier, enteric bacterial translocation, protease-antiprotease balance and mucosal histology, and also changes in pulmonary and liver endothelial barrier permeability were measured following intestinal ischemia for 40 min with 6 h of reperfusion in rats. RESULTS: Intestinal mucosal endothelial and epithelial permeabilities significantly increased in animals with I/R. Lexipafant prevented the increase in albumin leakage from blood to the mucosal interstitium and the intestinal lumen during reperfusion, and the mucosal albumin leakage from the gut lumen to blood during I/R. Bacterial translocation was frequently noted in animals with I/R, while only a few positive cultures were obtained in animals with I/R administered lexipafant. Less leakage of fluorescein isothiocyanate dextran 70,000 into the interstitial space and gut lumen in I/R animals with lexipafant pretreatment was found under fluorescein microscopy. Lexipafant also partly prevented C1 inhibitor, prekallikrein, and factor X consumption in I/R animals and partly prevented changes in pulmonary and liver albumin leakage. CONCLUSIONS: PAF seems to play an important role in I/R-associated intestinal dysfunction and the development of distant organ dysfunction, probably by triggering endothelial and epithelial barrier dysfunction. Furthermore, PAF seems to be partly involved in activation of the protease-antiprotease system. The use of PAF antagonists may provide a mode of treatment against I/R-associated organ dysfunction.     

Correlation between gut microbiota diversity and psychogenic erectile dysfunction

BackgroundTo analyze the distribution of gut microbiota in erectile dysfunction (ED) patients and explore the relationship between the diversity of gut microbiota and psychogenic ED.MethodsStool specimen were collected from 30 patients with ED and 30 healthy persons (healthy donors, HDs) and analyzed Paired end (PE) 300 sequencing on V3-V4 region sequences of bacterial 16S rRNA gene by using Illumina’s Miseq platform, whereby sequencing results were analyzed to assess differences in species composition and diversity. The analysis comprised five modules: sequencing data quality control, operational taxonomic units (OTU) species clustering and annotation, alpha diversity, beta diversity and the use of t-tests and analysis of linear discriminant analysis effect size (LEfSe) differences.ResultsThe International Index of Erectile Function (IIEF-5) score ranged between 8 and 21. The scores of ED patients were ≥11 and ≤20, and the mean value was 15.67±2.94. The flora diversity in the group of ED patients was significantly different from that of HDs (P<0.01), with the ED group having low bacterial diversity. There were no significant differences in the genus level between the ED and HD group, and abundant bacteria (TOP10) and core flora (90%). Comparison of total flora (the abundance >1%) display, Alloprevotella genera showed differences, whereby Alloprevotella was only be identified in the HD group. Erectile dysfunction and HD showed good separation and clustering respectively in principal component analysis, showing significant differences in two kinds of microflora. T-tests showed that six species were significantly different, and that in the ED group, streptococci and Subdoligranulum were significantly increasing, and Prevotella sp.9, Blautia, Lachnospiraceae NK4A136 groups and Roseburia were significantly lower. Analysis using LEfSe analysis revealed 24 species were significantly different between ED and HD groups.ConclusionsWhen gene sequencing was performed of ED and HD specimens, the microbial community structure and diversity showed significant differences, suggesting that ED specimen had lower gut microbiota diversity.     

Indocyanine green fluorescence measurement of intestinal transit and gut perfusion after intestinal manipulation

BACKGROUND AND AIMS: Postoperative ileus is a common and poorly understood problem of abdominal surgery. The aim of this study was to measure postoperative intestinal transit and to evaluate bowel wall perfusion by a novel in vivo indocyanine green (ICG)-fluorescence measurement following intestinal manipulation (IM). METHODS: Rats underwent a simple intestinal manipulation. Myeloperoxidase-positive cells in the muscularis were stained with the Hanker-Yates reaction and quantified histochemically. Bowel wall perfusion was determined directly and 24 h postoperatively using a laser-fluorescence detection unit. Intestinal transit was visualized 24 h after IM. RESULTS: IM resulted in a massive infiltration (155-fold) of neutrophils into the intestinal muscularis 24 h postoperatively. Bowel wall perfusion significantly decreased directly and 24 h following surgery (29 and 59%, respectively). Gastrointestinal transit was similarly impaired and showed a reduction to 40% of the control values 24 h after IM. CONCLUSION: IM of the rat small intestine caused an impairment in bowel wall perfusion and microcirculation and a significant decrease in gastrointestinal transit. The ICG fluorescence measurement using the described system proved to be a simple and reliable method to evaluate intestinal transit and bowel wall microcirculation in vivo.     

硫化氢在肠缺血-再灌注损伤大鼠肠黏膜屏障功能障碍中的作用

目的 观察硫化氢(H_2S)在肠缺血.再灌注损伤大鼠肠黏膜屏障功能障碍中的作用.方法 雄性Wistar大鼠24只,分为S(假手术)组、Ⅰ(缺血-再灌注)组,N(缺血-再灌注+NaHS)组(n=8),N组在再灌注前10 min静脉注射100 μmol/kg NaHs后按每小时1 mg/kg持续静脉注射直到再灌注2 h,S和Ⅰ组静脉注射相同体积的生理盐水.采用改良的酶学分光光度法测定血浆D-乳酸水平,采用分光光度法检测小肠黏膜超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)、丙二醛(MDA)、黄嘌呤氧化酶(XO)水平,敏感硫电极法检测硫化氢(H_2S)浓度.电镜下观察肠黏膜形态学改变,TUNEL染色观察小肠上皮细胞凋亡指数(AI),逆转录.聚合酶链反应(RT-PCR)法检测小肠黏膜组织胱硫醚-γ-裂解酶(CSE)、胱硫醚-β-合酶(CBS)、多聚ADP核糖合成酶(PARP)和细胞凋亡蛋白酶(Caspase)-3 mRNA的表达,蛋白质印迹法检测小肠黏膜PARP和Caspase-3蛋白水平.结果 N组D-乳酸含量、AI分别为(2.35±0.26)mg/L、(24.41±2.76)%,低于Ⅰ组、高于S组(P<0.01),两者正相关(r=0.892,P<0.01);N组MDA、XO分别为(9.17±0.35)nmol/mg、(9.94±0.41)U/g,低于Ⅰ组、高于S组(P<0.01),两者正相关(r=0.995,P<0.01);N组CSE mRNA、H_2S、SOD、MPO分别为(0.33±0.02)μmol/L、(35.27±3.14)μmol/L、(8.83±0.29)U/mg、(5.95±0.49)U/mg;N组CSE mRNA、H_2S、SOD水平均低于S组(P<0.01),N组H2S、SOD水平均高于Ⅰ组(P<0.01),N组MPO水平高于S组、低于Ⅰ组(P<0.01);N组活化的Caspase-3、PARP蛋白表达量分别为11.50±1.25、9.37±1.18,高于s组、低于Ⅰ组(P<0.01),两者正相关(r=0.785,P<0.01).结论 H_2S对肠缺血再灌注损伤大鼠肠黏膜屏障功能障碍有保护作用,其机制之一是减少中性粒细胞浸润和激活、肠上皮细胞氧化损伤水平,增加SOD清除氧自由基的活性,下调活化的Caspase-3和PARP蛋白表达.     

Urogenital disorders associated with gut failure and intestinal transplantation

PURPOSE: Intestinal transplantation has been increasingly performed in patients with short bowel syndrome and irreversible gut failure with successful outcomes. In parallel a common association was observed between gut failure and different urological disorders. To our knowledge this study is the first to address such an important clinical observation with special reference to the underlying disease. MATERIALS AND METHODS: The medical records of 175 consecutive adult intestinal recipients were reviewed. Data were compiled and described according to the documented urogenital disorder, cause of intestinal failure and treatment modality, including transplantation. RESULTS: Of the patients 43 experienced a total of 53 urogenital disorders for an overall incidence of 25%, including 24 (56%) who had the disorder before referral and 19 (44%) in whom the morbidity developed as a result of transplantation. Interestingly hypercoagulability, pseudo-obstruction, Crohn's disease and Gardner's syndrome were the underlying urogenital and intestinal disorder pathologies in 6.3% of the study patients. Treatment for prior urogenital disorders, including malignancy, precipitated intestinal failure in 3.4% of the referred patients. Reciprocally surgical treatment for the primary intestinal disease and management of gut failure by total parenteral nutrition, followed by transplantation, resulted in different urogenital complications in 17.7% of the total population with an 8.6% incidence of chronic renal failure. CONCLUSIONS: Gut failure and intestinal transplantation are commonly associated with different urogenital disorders. Accordingly a designated urological service should be considered part of the multidisciplinary team required for treating this unique population.     

肠功能障碍的营养支持

器官衰竭是指器官功能损害到不可逆转的程度,因此,在器官功能衰竭诊断标准中,各项指标都选定在器官功能障碍的"上限",以致被诊断为"多器官衰竭(MOF)"的患者病死率极高.此类诊断标准有失临床"早期发现,及时治疗"的要求.     

The effect of intestinal anastomosis on gut growth and maturation

We evaluated the effect of intestinal anastomosis without resection on gut morphometry (muscle thickness, villus height, and crypt depth), growth indices (DNA, protein, and protein:DNA ratio), and disaccharidase activity (maltase, sucrase, and lactase) in the growing animal. A group of 10 weanling Sprague-Dawley rats at 21 days of age was subjected to intestinal transection and anastomosis in the upper jejunum, 10 cm distal to the ligament of Treitz. A second group of 10 similar rats was used as a control group. All rats were fed a regular diet and kept under the same conditions. They were sacrificed 2 weeks later. Body weight, intestinal weight, and intestinal length measurements were obtained. The intestine was divided into two sections: preanastomotic (section A) and postanastomotic (section B) in the surgery group and equivalent sections A and B in the control group. Specimens were subjected to morphometric evaluation and mucosal scrapings for biochemical analysis. Despite significant weight gain in the control group, there were no differences in intestinal length, intestinal weight, and mucosal weight between the two groups. Muscle thickness, villus height, and crypt depth were significantly increased in the preanastomotic segment. Protein and DNA were also higher in the preanastomotic segment, but the protein:DNA ratio was less affected. There was significantly decreased enzymatic activity in the preanastomotic segment. Intestinal anastomosis has a significant effect on gut growth and maturation in the growing animal and may have important implications in the postoperative management of newborns and infants following intestinal surgery.     

The intestinal anastomotic insufficiency after the emergency gut resection

Results of anastomotic insufficiency prophylaxis during urgent gut resection in 576 patients were analyzed. The intraoperative transilluminative angiotensiometry and pulsmotorography were used as prognostic means. The permanent intramesenterial blockade, lymphotropic therapy, nasointestinal and transanal intubational decompression and local laseromagnetic therapy were used as prophylactic measures.     

Capillary leak syndrome with massive intestinal edema after appendectomy

Ileus and ascites developed in a previously healthy thirty-six year old man after appendectomy for acute appendicitis. Re-exploration revealed a grossly gangrenous appearing segment of terminal ileum and proximal colon that histologically showed only massive acellular submucosal edema with dilatation of lymphatics and serosal hyperemia without necrosis. Severe anasarca developed and the patient died after this second operation. Necropsy revealed submucosal edema of the remaining large and small intestines, anasarca, and pulmonary atelectasis. Regional enteritis, acute nonspecific ileitis, infectious enterocolitis, iatrogenic accident, and allergic phenomena were considered in the differential diagnosis. We believe this case is an example of the rare “capillary leak syndrome,” which has not been reported previously after appendectomy.     

Measurement of intestinal edema using an impedance analyzer circuit

BACKGROUND: Acute intestinal edema adversely affects intestinal transit, permeability, and contractility. Current resuscitation modalities, while effective, are associated with development of acute intestinal edema. Knowledge of levels of tissue edema would allow clinicians to monitor intestinal tissue water and may help prevent the detrimental effects of edema. However, there is no simple method to measure intestinal tissue water without biopsy. We sought to develop a tissue impedance analyzer to measure tissue edema, without the need for invasive biopsy. METHODS: Oscillating voltage input was applied to the analyzer circuit and an oscilloscope measured the voltage output across any load. Rats were randomized to three groups: sham, mild edema (80 mL/kg of NS resuscitation), and severe edema (80 mL/kg of NS resuscitation with intestinal venous hypertension). Intestinal edema was measured by wet-to-dry tissue weight ratio. Bowel impedance was measured and converted to capacitance using a standard curve. RESULTS: Acute intestinal edema causes a significant increase in bowel capacitance. This capacitance can be used to predict tissue water concentration. CONCLUSION: Using an impedance analyzer circuit, it is possible to measure intestinal edema reliably and quickly. This may prove to be a useful tool in the resuscitation of critically ill patients.     

硫化氢在肠缺血-再灌注损伤大鼠肝脏功能障碍中的作用

目的 观察硫化氢(H2S)在肠缺血-再灌注损伤大鼠肝脏功能障碍中的作用.方法 将24只雄性Wistar大鼠随机分为A(假手术)组、B(缺血-再灌注)组、C(缺血-再灌注+NABS)组(n=8).留取血浆测定H2S、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL),行肝脏组织匀浆检测脂质过氧化物(LPO)、髓过氧化物酶(MPO)、超氧物歧化酶(SOD)、丙二醇(MDA)和GSH/GSSG,光镜和电镜下观察肝脏组织病理变化,TUNEL染色观察肝细胞凋亡指数(AJ),逆转录.聚合酶链反应(RT-PCR)、Western blot法分别检测肝脏组织bcl-2、bax、Caspase-3、STAT3 mRNA和蛋白、pSTAT3和cytochrome C蛋白的表达.结果 C组ALT、AST、肝脏组织MPO、浸润的中性粒细胞数、MDA、LPO、AI、pSTAT3蛋白、Caspase-3mRNA、Caspase-3蛋白、bax mRNA、bax蛋白表达量分别为(47.63±5.04)U/L、(57.63±5.04)U/L、(1.71±0.17)U/mg、(14.13±1.64)个/视野、(23.42±0.69)nmol/mg、(140.13±11.33)nmol/mg、(23.39±1.40)%、0.222±0.019、0.477±0.050、0.214±0.009、0.076±0.004、0.419±0.012,均显著低于B组,高于A组(P<0.01),均与H2S负相关,与AJ正相关.C组H2S、GSH/GSSG、SOD、cytochrome C蛋白、bcl-2 mRNA、bcl-2蛋白表达量分别为(35.27±3.14)μmol/L、9.78±0.56、(90.70±5.69)U/mg、1.132±0.076、0.325±0.052、0.377±0.034,均显著高于B组,低于A组(P<0.01),均与AI负相关,与H2S正相关.pSTAT3与bax、Caspase-3基因表达正相关,与cytochrome C蛋白、bcl-2基因表达负相关.结论 H2s对肠缺血再灌注损伤大鼠肝脏功能障碍起保护作用.