The role of vagal innervation on the early development of postoperative ileus in mice.

BACKGROUND: Postoperative ileus (POI) involves an intestinal inflammatory response that is modulated by afferent and efferent vagal activation. We aimed to identify the potential influence of the vagus nerve on POI by tracking central vagal activation and its role for peripheral inflammatory changes during the early hours after surgery. METHODS: C57BL6 mice were vagotomized (V) 3-4 days prior to experiments, while control animals received sham vagotomy (SV). Subgroups underwent either laparotomy (sham operation; S-POI) or laparotomy followed by standardized small bowel manipulation to induce postoperative ileus (POI). Three hours and 9 h later, respectively, a jejunal segment was harvested and infiltration of inflammatory cells in intestinal muscularis was evaluated by fluorescein isothiocyanate (FITC) avidin and myeloperoxidase (MPO) staining. Moreover, the brain stem was harvested, and central nervous activation was investigated by Fos immunochemistry in both the nucleus of the solitary tract (NTS) and the area postrema (AP). Data are presented as mean ± SEM, and a p < 0.05 was considered statistically significant. KEY RESULTS: Three hour experiments revealed no significant differences between all experimental groups, except MPO staining: 3 h after abdominal surgery, there were significantly more MPO-positive cells in vagotomized S-POI animals compared to sham-vagotomized S-POI animals (26.7 ± 7.1 vs. 5.1 ± 2.4, p < 0.01). Nine hour postoperatively intramuscular mast cells (IMMC) were significantly decreased in the intestinal muscularis of V/POI animals compared to SV/POI animals (1.5 ± 0.3 vs. 5.9 ± 0.2, p < 0.05), while MPO-positive cells were increased in V/POI animals compared to SV/POI animals (713.2 ± 99.4 vs. 46.9 ± 5.8, p < 0.05). There were less Fos-positive cells in the NTS of V/POI animals compared to SV/POI animals (64.7 ± 7.8 vs. 132.8 ± 23.9, p < 0.05) and more Fos-positive cells in the AP of V/POI animals compared to SV/POI animals 9 h postoperatively (38.0 ± 2.0 vs. 13.7 ± 0.9, p < 0.001). CONCLUSIONS AND INTERFERENCES: Afferent nerve signaling to the central nervous system during the development of early POI seems to be mediated mainly via the vagus nerve and to a lesser degree via systemic circulation. During the early hours of POI, the intestinal immune response may be attenuated by vagal modulation, suggesting interactions between the central nervous system and the intestine.

Effect of bowel preparation on intestinal permeability and inflammatory response during postoperative ileus in mice.

BACKGROUND: Postoperative ileus entails pathophysiological changes in mucosal permeability and an intestinal inflammatory immune response. We hypothesized that preoperative selective decontamination of the digestive tract combined with preoperative mechanical bowel preparation might be advantageous to prevent or reduce permeability changes and immune response in postoperative ileus. METHODS: Postoperative ileus was induced in mice by standardized small bowel manipulation. Intervention groups received selective decontamination and/or intestinal lavage with normal saline simulating mechanical bowel preparation before postoperative ileus induction. At 1, 3, and 9 hours after surgery, ileum samples were harvested for measurements of fluorescein (332 Da) permeability, quantification of tumor necrosis factor α-mRNA level, and leukocyte infiltration of the intestinal wall. RESULTS: Mucosal fluorescein permeability increased at 1 hour (8.6 ± 1.1 vs 5.9 ± 0.9 10-6 cm/s; P < .01) and 3 hours (8.5 ± 0.6 vs 6.5 ± 0.2 10-6 cm/s; P < .05) after induction of postoperative ileus. This increase was prevented by mechanical bowel preparation and selective decontamination+mechanical bowel preparation interventions at both points in time. Expression of tumor necrosis factor α was more than 2-fold increased (P < .05) in the very early phase after induction of postoperative ileus but did not occur in mechanical bowel preparation-pretreated animals. Myeloperoxidase staining revealed that mechanical bowel preparation inhibited postoperative ileus-associated leukocyte infiltration of the intestinal muscularis at 3 and 9 hours after surgery, but not selective decontamination + mechanical bowel preparation treatment. The number of leukocytes after mechanical bowel preparation-only treatment remained at the level of sham-controls. CONCLUSION: Mechanical bowel preparation prevents permeability and leukocyte infiltration of the intestinal wall in the early phase of postoperative ileus in mice.

Time-Dependent Alterations of Gut Wall Integrity in Small Bowel Obstruction in Mice.

BACKGROUND: Small bowel obstruction (SBO) is one of the most common disorders in surgical emergency departments. Without resolution of the obstructed bowel segments, patients may develop multiorgan failure. The aim of this study was to investigate whether morphological damage of the intestinal wall during SBO may lead to molecular translocation and how this may impair intestinal motility. METHODS: C57Bl6 mice were laparotomized, and the small intestine was ligated 5 cm oral to the coecum for SBO. Controls received minilaparotomy only. Animals were sacrificed 3 h, 9 h, and 24 h after SBO. Morphological changes were evaluated on hematoxylin and eosin histology by a standardized score. Intestinal motility was determined by recording intraluminal pressure of the small intestine in vitro. Permeability was measured by fluorospectroscopy and ELISA of blood samples after oral gavage with fluorescein isothiocyanate (FITC)-dextrane and horse radish peroxidase. Data are mean ± SD. RESULTS: Three hours after SBO, FITC-dextrane uptake was increased to 187.6 ± 15.2 ng/mL compared to controls (P = 0.011). At 9 h, uptake of horse radish peroxidase (23.0 ± 8.6 ng/mL, 9.0 ± 6.3 ng/mL, P = 0.039) and FITC-dextrane (86.8 ± 17.8 ng/mL, 62.0 ± 1.6 ng/mL, P = 0.029) was higher compared to controls. Motility was increased to 162.2 ± 20.2 area under the curve (AUC) compared to 121.3 ± 20.3 AUC in controls, P = 0.009 and an increased histology score was observed at 9 h (3.2 ± 1.8 versus 0.6 ± 0.7, P = 0.003). Twenty-four hours after SBO, histology score was 3.8 ± 1.7, which was higher than 0.9 ± 0.7 in controls (P = 0.001). Intestinal motility was decreased 24 h after SBO compared to sham controls (146.0 ± 21.4 AUC versus 198.9 ± 21.2 AUC, P = 0.003). CONCLUSIONS: SBO entails a time dependent epithelial damage to the mucosa. In parallel, molecular changes in the gut mucosal barrier occur as early as 3 h after the onset of SBO with a subsequent increase in permeability. Initial intestinal hypermotility is followed by a decrease in motility.

Timing of surgery in ulcerative colitis in the biologic therapy era-the patient's perspective.

BACKGROUND: There is no general consensus regarding the ideal timing of surgery in patients with refractory ulcerative colitis (UC). Decision-making and timing of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is influenced by treating physicians and patients themselves. The aim of this study was to determine whether or not patients would have preferred the operation to be performed earlier, at the same time, or at a later point of time and to determine the reasons for their preference. METHODS: Clinical data of 193 patients with UC who have undergone IPAA were documented in a prospective database at our institution between 2004 and 2015. From this database, 190 patients were identified and a standardized custom-made questionnaire was mailed for follow-up survey. Patients who did not respond were called by telephone and encouraged to complete the questionnaire. RESULTS: One hundred nine questionnaires were eligible for analysis (57.4%). Average time between diagnosis and surgery was 11.2 ± 10.8 years (mean ± SD). Indications for surgery were refractory disease (70.6%), colitis-associated colorectal cancer (11.0%), high-grade dysplasia or stenosis (11.9%), and septic complications of UC (6.4%); 39 of 77 patients (50.6%) with refractory UC reported to have preferred their operation to be carried out earlier as it was actually performed (16.8 ± 11.9 months). Refractory course of the disease was identified as a predictor for a retrospectively desired earlier surgical approach (p = 0.014). CONCLUSION: A substantial proportion of patients felt that they should have undergone surgery earlier than actually performed. It appears that timing of the decision to undergo surgery is suboptimal. This situation may be improved by earlier surgical consultation in the course of the disease.

Enteral Nutrition Support Reduces the Necessity of Total Parenteral Nutrition to Reach Patient-Specific Caloric Goals Postpancreaticoduodenectomy.

OBJECTIVES: Pancreaticoduodenectomy (PD) is associated with significant rates of postoperative complications. Although there is evidence that enteral nutrition support (ENS) may reduce postoperative sepsis, the true value of ENS in the abrogation of septic complications remains controversial. The aim of our study is to investigate the postoperative outcome of patients post-PD with and without ENS. METHODS: Using our prospective institutional database, we identified 202 patients from 2001 through 2009 who underwent PD. Of the 202 patients, 121 matched our inclusion criteria. In total, 67 of 121 (55.4%) patients received ENS, whereas 54 (44.6%) patients had no ENS and served as controls. Postoperative morbidity and mortality were recorded and analyzed. RESULTS: No significant differences were found in the postoperative morbidity of the patients. The anastomotic leak rate was 13% in both the ENS and control groups (P = 0.846). There was no difference in mortality within the two groups (4% vs 5%, P = 0.881). Significantly more patients in the control group received total parenteral nutrition (P = 0.033). CONCLUSIONS: ENS is not associated with lower rates of postoperative morbidity and mortality. It does, however, reduce the necessity of additional total parenteral nutrition to reach patient-specific caloric goals.

Hartmann's procedure or primary anastomosis?

Perforation following acute diverticulitis is a typical scenario during the first attack. Different classification systems exist to classify acute perforated diverticulitis. While the Hinchey classification, which is based on intraoperative findings, is internationally best known, the German Hansen-Stock classification which is based on CT scan is widely accepted within Germany. When surgery is necessary, sigmoid colectomy is the standard of care. An important question is whether patients should receive primary anastomosis or a Hartmann procedure subsequently. A priori there are several arguments for both procedures. Hartmann's operation is extremely safe and, therefore, represents the best option in severely ill patients and/or extensive peritonitis. However, this operation carries a high risk of stoma nonreversal, or, when reversal is attempted, a high risk in terms of morbidity and mortality. In contrast, primary anastomosis with or without loop ileostoma is a slightly more lengthy procedure as normally the splenic flexure needs to be mobilized and construction of the anastomosis may consume more time than the Hartmann operation. The big advantage of primary anastomosis, however, is that there is no need for the potentially risky stoma reversal operation. The most interesting question is when to do the Hartmann operation or primary anastomosis. Several comparative case series were published showing that primary anastomosis is feasible in many patients. However, no randomized trial is available to date. It is of note, that all non-randomized case series are biased, i.e. that patients in better condition received anastomosis and those with severe peritonitis underwent Hartmann's operation. This bias is undoubtedly likely to be present, even if not obvious, in the published papers! Our own data suggest that this decision should not be based on the extent of peritonitis but rather on patient condition and comorbidity. In conclusion, sigmoid colectomy and primary anastomosis is feasible and safe in many patients who need surgery for perforated diverticulitis, particularly when combined with loop ileostomy. Based on our own published analysis, however, we recommend performing Hartmann's operation in severely ill patients who carry substantial comorbidity, while the extent of peritonitis appears not to be of predominant importance.

Immunonutrition with long-chain fatty acids prevents activation of macrophages in the gut wall.

BACKGROUND: Immune cells and inflammatory mediators are released from the gastrointestinal tract into the mesenteric lymph during sepsis causing distant organ dysfunction. Recently, it was demonstrated that macrophages in the gut wall are controlled by the vagus nerve, the so-called cholinergic anti-inflammatory pathway. AIM: This study aims to investigate whether an enteral diet with lipid prevents the activation of leukocytes in the gut wall. METHODS: Mesenteric lymph was obtained from rats, receiving an enteral infusion of glucose or glucose + lipid before and after lipopolysaccharide (LPS) injection. Immune cells in mesenteric lymph were analyzed with fluorescence-activated cell sorting before and after LPS injection. Mesenteric lymph leukocytes from rats receiving enteral glucose with or without lipid were stimulated in vitro with LPS and tumor necrosis factor (TNF)α was measured in the supernatant. RESULTS: The release of macrophages from the gut during sepsis was not significantly different in animals enterally treated with glucose or lipid. However, the release of TNFα from mesenteric lymph leukocytes after in vitro LPS stimulation was more than 3-fold higher in the glucose group compared to the lipid-treated group. CONCLUSIONS: During sepsis, activated macrophages are released from the gut into mesenteric lymph. However, an enteral diet with lipid is able to suppress the inflammatory cytokine release from mesenteric lymph leukocytes.

Vagal innervation and early postoperative ileus in mice.

INTRODUCTION: Postoperative ileus is characterized by infiltrates of leukocytes in the gut wall 24 h after surgery, which is subject to vagal modulation. We hypothesized that vagal modulation is irrelevant during earlier hours of postoperative ileus and aimed to determine whether afferent neuronal feedback to the central nervous system is altered by vagal innervation during this early period. METHODS: C57BL6 mice were laparotomized and received standardized small bowel manipulation to induce postoperative ileus. Subgroups were vagotomized 3-4 days prior to experiments while control animals were sham-operated. Three or 9 h later a 2-cm jejunal segment was harvested for multi-unit mesenteric afferent nerve recordings in vitro. Intestinal motility was monitored continuously and intestinal muscularis was stained for myeloperoxidase to determine infiltration of leukocytes. RESULTS: Peak amplitudes of intestinal motility and afferent nerve discharge at baseline were not different in all subgroups. Afferent discharge to 5-HT (500 µM) was virtually absent following vagotomy at 3 and 9 h of postoperative ileus (POI) compared to controls (p < 0.05). Maximum afferent nerve discharge to bradykinin and peak firing during maximum distension at 60 mmHg was not different in all subgroups while luminal distension from 10 to 30 mmHg was lower at 3 h of POI following vagotomy compared to controls (p < 0.05). The number of myeloperoxidase positive cells was similar at 3 h of POI in both subgroups; however, at 9 h of POI, ileus counts were increased to 713 ± 99 cells following vagotomy compared to 47 ± 6 cells per square millimeter in control animals. CONCLUSIONS: Vagal afferents mediate sensitivity to low-threshold distension and 5-HT during postoperative ileus but not to high-threshold distension and bradykinin. Vagal inhibition of the intestinal immune response is present at 9 h but not detectable earlier, i.e., at 3 h of postoperative ileus when spinal reflex inhibition may prevail.

Co-morbidity and postsurgical outcome in patients with perforated sigmoid diverticulitis.

INTRODUCTION: It was previously reported that in patients with acute perforated diverticulitis with Hinchey categories I to III sigmoidectomy with primary anastomosis (PA) is superior to Hartmann's procedure (HP) as later closure of colostomy involves substantial morbidity. We evaluated our experience with PA for patients with perforated diverticulitis over a 10-year period and aimed to investigate whether Hinchey category or co-morbidity are more relevant for postoperative outcome. METHODS: Records of all patients treated at our institution for sigmoid diverticulitis between 1996 and 2006 were retrieved from an in-hospital database (N = 787, median age 66 years, range 30 to 94, female:male ratio 1.3:1); 73 patients who underwent immediate emergency surgery for perforated diverticulitis were included in this study. American Society of Anesthesiology (ASA) classification to gauge co-morbidity and Hinchey category for intraoperative extent of inflammation were evaluated as regards their relevance for postoperative mortality and major complications. RESULTS: 47 patients (64%) underwent sigmoid colectomy and PA, which was combined with loop ileostomy in 11 patients (15%). Sigmoid colectomy and HP was performed in 26 patients (36%). Major postoperative complications occurred in 26 patients (36%). In the PA group, 10 of 47 patients (21%) had anastomotic leakage. Three leakages occurred despite a loop ileostomy. Anastomotic leakage was independent of Hinchey category (Hinchey I: three patients, Hinchey II: four patients, Hinchey III: three patients, n.s.), but associated with co-morbidity (one patient ASA II, six patients ASA III, three patients ASA IV, P < 0.05). Total mortality was 12%. Seven patients died after HP and two patients after PA. No mortality was observed in PA patients with loop ileostomy. CONCLUSIONS: Emergency surgery for perforated sigmoid diverticulitis is associated with high morbidity and mortality rates. Anastomotic leakage was associated with patient co-morbidity rather than with intraoperative Hinchey category, suggesting that the decision to perform PA should better be based on patient's general condition rather than on intraoperative extent of inflammation.

Extrinsic afferent nerve sensitivity and enteric neurotransmission in murine jejunum in vitro.

Enteric and extrinsic sensory neurons respond to similar stimuli. Thus they may be activated in series or in parallel. Because signal transmission via synapses or mediator release would depend on calcium, we investigated its role for extrinsic afferent sensitivity to chemical and mechanical stimulation. Extracellular multiunit afferent recordings were made in vitro from paravascular nerve bundles supplying the mouse jejunum. Intraluminal pressure and afferent nerve responses were recorded under control conditions and under four conditions designed to interfere with enteric neurotransmission. We found that phasic intestinal contractions ceased after switching perfusion to Ca(2+)-free buffer with or without a purinergic P2 receptor antagonist, pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) (PPADS) or cadmium (blocking all Ca(2+)-channels) but not following omega-conotoxin GVIA (N-type Ca(2+)-channel blocker). Luminal HCl (pH 2) and 5-HT (500 microM) evoked peak firing of 17 +/- 4 impulses per second (imp/s) (n = 10) and 21 +/- 4 imp/s (n = 13) under control conditions. These responses were reduced to 4 +/- 2 imp/s and 5 +/- 2 imp/s by cadmium (n = 7, P < 0.05), to 7 +/- 2 imp/s and 6 +/- 1 imp/s by Ca(2+)-free perfusion (n = 6, P < 0.05), and to 3 +/- 1 imp/s and 4 +/- 1 imp/s by Ca(2+)-free perfusion with PPADS (n = 6, P < 0.05). Responses were unchanged by omega-conotoxin GVIA. Mechanical ramp distension of the intestinal segment to 60 cmH(2)O was not altered by any of the experimental conditions. We concluded that HCl and 5-HT activate extrinsic afferents via a calcium-dependent mechanism, which is unlikely to involve enteric neurons carrying N-type calcium channels. Extrinsic mechanosensitivity is independent of enteric neurotransmission. It appears that cross talk from the enteric to the extrinsic nervous system does not mediate extrinsic afferent sensitivity.

Differential sensitization of afferent neuronal pathways during postoperative ileus in the mouse jejunum.

BACKGROUND: Postoperative ileus induces reflex inhibition of gastrointestinal motility and an intestinal inflammatory response. We aimed to determine whether afferent sensitivity is increased during postoperative ileus and whether alterations are cyclooxygenase-2 (COX-2)-dependent. METHODS: C57BL/6 mice underwent laparotomy followed by standardized small bowel manipulation to induce ileus or sham treatment. After 24 hours, extracellular multiunit mesenteric afferent nerve discharge was recorded in vitro from 2-cm segments of jejunum. Fos immunoreactivity was determined for neuronal activation in the vagal nucleus of the solitary tract (nTS) of the brain stem and leukocyte infiltration in the intestinal muscularis by myeloperoxidase stains. RESULTS: Serosal bradykinin (1 microM) was followed by an increase in afferent discharge to 65 +/- 5 imp x s(-1) in ileus segments compared with 37 +/- 6 imp x s(-1) in sham controls (P < 0.05). The response was attenuated to 31 +/- 7 imp x s(-1) after the selective COX-2 inhibitor 5,5-dimethyl-3-(flurorophenyl)-4-(4-methylsulfonyl) phenyl-2(5H)-furanone (DFU) in ileus segments. Afferent firing during ileus was augmented at luminal distension at 20 mm Hg but not at pressures up to 60 mm Hg. The number of Fos-positive neurons in the nTS was 110 +/- 45 during ileus compared with 7 +/- 4 in sham controls (-7.32 mm from bregma, P < 0.05) and did not differ after DFU. The intestinal muscularis contained more leukocytes during ileus compared with ileus segments after DFU and controls (both P < 0.05). CONCLUSION: This study provides direct evidence from afferent nerve recordings that sensitivity to bradykinin, which stimulates predominantly spinal afferents, is augmented during postoperative ileus involving a COX-2 pathway. Vagal afferents were also sensitized because low-threshold mechanosensitivity and neuronal activation in the nTS were increased.

Postoperative complications have little influence on long-term quality of life in Crohn's patients.

PURPOSE: The purpose of the study was to determine the influence of postoperative complications on long-term quality of life in patients after abdominal operations for Crohn's disease. MATERIALS AND METHODS: From 1996 to 2002, 305 Crohn's patients underwent abdominal surgery, and 66 patients developed postoperative complications. Quality of life was studied using a standardized questionnaire and four quality of life instruments. Sixty-six Crohn's patients with uneventful postoperative course matched for age, and follow-up time served as controls. RESULTS: Forty-eight patients (81%) in the complication group (32 major and 16 minor) and 43 patients (75%) in the control group answered the questionnaire. Postoperative follow-up time was 42 (10-94) and 41 months (13-94; median (range)). Quality of life was comparable between groups, except on the subscale "physical functioning" of the Short-form 36 on which patients with minor and major complications showed impaired quality of life compared to controls (67+/-6, 69+/-4, and 84+/-2%; mean+/-standard error of the mean; both p<0.05 vs controls). The incidence of Crohn's disease-related symptoms at follow-up was unaffected by complications (minor 63%, major 56% vs controls 70%; both not significant). CONCLUSION: Postoperative complications after abdominal operations for Crohn's disease do not impair long-term quality of life in general but may affect specific dimensions of quality of life like patients' physical function.

Long-term quality of life in patients with Crohn's disease and perianal fistulas: influence of fecal diversion.

PURPOSE: Symptomatic perianal fistulas impair quality of life in patients with Crohn's disease. Fecal diversion improves symptoms but may impair quality of life. This study was designed to compare long-term quality of life in patients with Crohn's disease with symptomatic perianal fistulas who were treated with or without fecal diversion. METHODS: From 1996 to 2002, perianal fistulas were treated in 116 patients with Crohn's disease. A questionnaire, including four quality of life instruments, was mailed to each patient (Short-Form General Health Survey, Gastrointestinal Quality of Life Index, Cleveland Global Quality of Life Score, Short Inflammatory Bowel Disease Questionnaire). RESULTS: Questionnaires were returned by 77 of 116 patients (66 percent). Thirty-four of these patients had undergone fecal diversion, whereas 43 had not. Median follow-up was 49 (range, 18-97) months in diverted and 44 (range, 14-98) months in undiverted patients (not significant). In the diverted group, 44 percent complained of Crohn's disease-related symptoms, which was less compared with 79 percent in undiverted patients (P < 0.05). Diverted patients achieved 68 +/- 1 percent of the maximum possible score on the Gastrointestinal Quality of Life Index compared with 60 +/- 2 percent in undiverted patients (mean +/- standard error of the mean; P < 0.001); diverted patients scored better on the subscale "gastrointestinal symptoms" of the Gastrointestinal Quality of Life Index (81 +/- 1 percent vs. 67 +/- 2 percent; P < 0.001). There was no difference in the Short Inflammatory Bowel Disease Questionnaire between diverted and undiverted patients except for the subscale "bowel function" (91 +/- 2 percent vs. 76 +/- 2 percent; P < 0.0001). No difference in quality of life was detected by the Short-Form General Health Survey and Cleveland Global Quality of Life Score. CONCLUSIONS: In the investigated population of patients with Crohn's disease, quality of life seems to be similar or potentially superior in diverted patients suffering from perianal fistulas compared with undiverted patients. A diverting stoma, therefore, may improve quality of life in patients with severe perianal Crohn's disease.

Enteral immunonutrition during sepsis prevents pulmonary dysfunction in a rat model.

BACKGROUND: Sepsis often results in severe pulmonary dysfunction. Via the thoracic duct, the lung is the first organ exposed to gut-derived inflammatory mediators released into mesenteric lymph during sepsis. AIM: To investigate whether an enteral immunonutrition during sepsis improves pulmonary function. METHODS: Mesenteric lymph was obtained from lymph fistula donor rats after intra peritoneal (i.p.) saline (control lymph) or lipopolysaccharide (sepsis lymph) injection. Sepsis lymph was also collected during enteral immunonutrition with omega-3 enriched, long-chain fatty acids (SMOF lipid). Control, sepsis, or sepsis-SMOF lymph was reinfused into the jugular vein of separate recipient rats. The lungs were then harvested, stained with hematoxylin-eosin, and analyzed for: (1) perpendicular parenchyma thickness of the alveolar wall; (2) myeloperoxidase-positive cells; and (3) terminal deoxynucleotidyl transferase Biotin-dUTP nick end labeling (TUNEL)-positive cells. RESULTS: Enteral immunonutrition during sepsis reduced the release of TNFalpha into mesenteric lymph by about 4.5-fold within the first 2 h. Infusion of sepsis lymph into recipient rats induced thickening of alveolar walls, inflammatory reaction, and apoptosis. Infusion of sepsis lymph obtained during enteral immunonutrition did not cause anatomical changes, induced only a mild inflammatory reaction, and prevented apoptosis in the lungs of recipient rats. CONCLUSIONS: Mediators in sepsis lymph induce pulmonary dysfunction such as an increased distance for oxygen transport, inflammatory reaction, and apoptosis. The lung may be protected by an enteral immunonutrition containing long-chain fatty acids.

Olive oil is more potent than fish oil to reduce septic pulmonary dysfunctions in rats.

BACKGROUND: Abdominal sepsis is frequently the cause of severe pulmonary dysfunction. Via the thoracic duct, the lung is the first organ exposed to gut-derived mediators released into the mesenteric lymph. AIM: The aim of this study is to investigate whether an enteral immunonutrition with long chain triglycerides prevents septic pulmonary dysfunctions. MATERIALS AND METHODS: Mesenteric lymph was obtained from lymph fistula donor rats during sepsis (lipopolysaccharides [LPS], 5 mg/kg i.p.) with or without enteral immunonutrition (1% of olive oil or 1% of fish oil). Sepsis lymph was then reinfused into the jugular vein of separate recipient rats. Thereafter, the lung tissue was analyzed for the distance of oxygen diffusion, inflammatory response, and cell apoptosis. RESULTS: Sepsis significantly increased TNFalpha release into the mesenteric lymph, whereas an enteral immunonutrition with olive oil significantly reduced the TNFalpha release into the mesenteric lymph by more than five-fold. Sepsis lymph induced a significant increase in alveolar wall thickness, inflammatory reaction, and apoptosis; whereas sepsis lymph collected during olive oil resorption prevented the thickening of the alveolar walls and induced only a mild inflammation, being more potent than fish oil to reduce septic pulmonary dysfunction. CONCLUSIONS: Mediators in the sepsis lymph induce pulmonary dysfunction. The lung may be protected by an enteral immunonutrition containing long chain triglycerides such as olive oil.

Postoperative colonic motility after tropisetron and a standardized meal in patients undergoing conventional colorectal surgery.

BACKGROUND: Early postoperative enteral nutrition is advantageous for the recovery of colonic motility but may be limited by abdominal distension, nausea, and vomiting. We aimed to investigate the tolerance of a standardized meal after pretreatment with the 5-hydroxytryptamine-3-receptor antagonist tropisetron and to study the concomitant colonic motility. METHODS: Colonic motility and tone were recorded on postoperative day 1 to 3 with a combined manometry/barostat recording catheter in 12 patients who underwent open colorectal surgery with an anastomosis in the distal colon or rectum. The study protocol consisted of 30 min of baseline recordings followed by 5 mg of tropisetron intravenously. Then, motility was recorded for another 30 min before patients ingested a standardized meal to trigger the gastrocolonic response. Postprandial motility was recorded for the subsequent 60 min. RESULTS: The colonic motility index increased after administration of tropisetron on all three postoperative days (day 1: 34+/-11 vs 122+/-48, day 2: 55+/-19 vs 101+/-25, and day 3: 42+/-16 vs 93+/-33 mmHg/min; p<0.05). No further increase of the motility index was observed postprandially. Frequency and amplitude of contractions were virtually unaffected by tropisetron and the meal. Barostat bag volume decreased postprandially in the proximal bag on the third, and in the distal bag on the first and second postoperative day (p<0.05). Patients' condition was unaffected by the standardized meal after tropisetron administration. CONCLUSIONS: Tropisetron may enhance colonic motility in the early postoperative period; however, the gastrocolonic response was impaired thereafter. High caloric food intake is well tolerated early after surgery after tropisetron pretreatment.

Systemic capsaicin inhibits neuronal activation in the brainstem during postoperative ileus in the mouse.

INTRODUCTION: Neuronal inhibitory reflex mechanisms contribute to postoperative ileus after abdominal surgery. During this condition, sensory neurons in the brainstem are activated. We aimed to determine the contribution of capsaicin-sensitive afferents to central vagal sensitivity in mice during postoperative ileus. MATERIALS AND METHODS: Under enflurane anesthesia, C57BL/6 mice were laparotomized and the small bowel was manipulated to induce ileus or was left untouched as a sham-treatment group. A subgroup of ileus animals was pre-treated with Capsaicin (1 microm/kg, i.p.) 48 h before small bowel manipulation. The animals were killed 24 h later and the brainstem was removed for Fos immunohistochemistry, which was quantified in the nucleus of the solitary tract (nTS). Spontaneous jejunal motility was recorded in vitro. Leukocyte infiltration in the intestinal muscularis was studied by myeloperoxidase staining as an index of postoperative inflammation. RESULTS: There were 30+/-9 Fos-positive neurons counted in the nTS after ileus and 6+/-2 in sham controls (Bregma -7.70 mm, P=0.01). A reduction to 8+/-3 was observed after Capsaicin pre-treatment in ileus animals (P<0.05). Peak amplitudes of spontaneous jejunal motility were 2+/-0.3 cmH2O during postoperative ileus, 3+/-0.6 cmH2O after ileus with capsaicin pre-treatment, and 10+/-2 cmH2O in control animals (N=6, both P<0.05). The number of leukocytes infiltrating the muscularis was 39+/-9/mm2 during ileus and 1.8+/-1/mm2 in controls (mean+/-SEM, P<0.01, N=6). After capsaicin, this number increased to 72+/-28/mm2 in ileus animals (P<0.05 vs control animals, N=7). CONCLUSION: The inhibition of capsaicin-sensitive vagal afferent pathways appears to boost rather than to attenuate the inflammatory response during postoperative ileus, while intestinal motility remained unchanged. This suggests a protective role of the capsaicin-sensitive afferent innervation for the inflammatory phase of postoperative ileus.

Postoperative colonic motility increases after early food intake in patients undergoing colorectal surgery.

BACKGROUND: Stimulation of colonic motility by the gastrocolonic response may help to reduce inhibition of gastrointestinal motility after colorectal surgery. We aimed to investigate whether postoperative colonic motility is increased after early food intake. METHODS: Nineteen patients undergoing colorectal surgery and 7 healthy volunteers were investigated. Colonic motility was recorded with a combined manometry/barostat system, and the effect of a standard 500-kcal meal was evaluated once in healthy volunteers and in 15 patients on the first and second postoperative day. Four patients remained unfed, serving as controls. RESULTS: In patients, the colonic motility index increased from 12 +/- 5 at baseline to 65 +/- 24 mm Hg after the meal on postoperative day 1 (mean +/- SEM; P < .01), while barostat bag volumes decreased, indicating a rise in colonic tone. On day 2, the motility index was 62 +/- 17 mm Hg at baseline and did not change after the meal. In unfed controls, no change was observed during colonic motility recordings on both postoperative days. In healthy volunteers, the colonic motility index increased from 98 +/- 52 at baseline to 151 +/- 58 mm Hg postprandially (P < .05). CONCLUSIONS: As in healthy volunteers, there is a potential to stimulate colonic motility by early food intake in postoperative patients. This may help to improve prolonged colonic motility disorders after colorectal surgery.

Mesenteric lymph collected during peritonitis or sepsis potently inhibits gastric motility in rats.

Gastrointestinal motility is strongly inhibited during peritonitis or sepsis and proinflammatory cytokines released into mesenteric lymph during an acute gastrointestinal insult mediate systemic responses. We investigated whether mesenteric lymph collected during peritonitis or sepsis inhibits gastric motility and gastric emptying. Mesenteric lymph was collected for 12 hours from three experimental groups: vehicle (saline, 1 ml, intraperitoneally [ip], control lymph), peritonitis (0.5% acetic acid, 1 ml, ip, peritonitis lymph), and sepsis (lipopolysaccharide [LPS], 5 mg/kg, 1 ml, ip, sepsis lymph). Gastric motility and gastric emptying were measured in recipient rats in response to lymph injections into the jugular vein. Quantitative polymerase chain reaction (PCR) for tumor necrosis factor alpha (TNFalpha) gene expression in the jejunum and in lymph cells were measured during sepsis. Mesenteric lymph flow significantly increased during peritonitis or sepsis (lymph flow [ml] per 60 minutes; control 2.45 +/- 0.04; peritonitis 2.67 +/- 0.07; sepsis 3.25 +/- 0.1, p < 0.01 vs. control). Injection of peritonitis or sepsis lymph (1 ml) produced a significant and prolonged inhibition of gastric motility in recipient rats (decrease in intragastric pressure and duration: control lymph -0.14 +/- 0.05 cm H(2)O, 1.89 +/- 1.31 minutes; peritonitis lymph: -0.56 +/- 0.06 cm H(2)O, 9.9 +/- 0.9 minutes; sepsis lymph: -0.51 +/- 0.05 cm H(2)O, 6.9 +/- 0.6 minutes; p < 0.001 vs. control for all comparisons). Gastric emptying was significantly inhibited by continuous infusion of sepsis lymph (3 ml per 60 minutes; gastric emptying: saline 81% +/- 4%; control lymph: 80% +/- 6%; sepsis lymph: 44% +/- 10%; p < 0.001 vs. control). TNFalpha gene expression in the gut wall of the jejunum increased during sepsis over 90-fold within the first 2 hours and decreased continuously thereafter (relative TNFalpha mRNA transcription: basal 1.0 +/- 0.05; LPS 2 hours: 91.9 +/- 2.6, p < 0.001 vs. basal; 12 hours: 24.7 +/- 16.8, not significant [NS]; 24 hours: 7.0 +/- 3.4, NS). In conclusion, mediators in mesenteric lymph, possibly cytokines, may be responsible for the inhibition of gastric motility during peritonitis or sepsis. Because the composition of mesenteric lymph probably reflects the interstitial fluid of the gut wall, monitoring visceral lymph might be an extremely beneficial tool to determine mediators released during impaired gut wall function.