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At least 19 recordsLinked to original sources
PubMed2026

Glial Connexin-43 Is a Pathogenic Mechanism Promoting Gut Inflammation in Postoperative Ileus Induced by Gut Surgical Manipulation With Potential Relevance to Humans.

BACKGROUND & AIMS: Abdominal surgery often precipitates postoperative ileus (POI), a frequent and severe gastrointestinal (GI) motility disorder, through mechanisms that involve intestinal inflammation. Emerging data show that enteric glia acquire a reactive phenotype that aggravates POI, but how glia exert this effect remains unclear. Enteric glia express connexin-43 hemichannels (gCx43), which are implicated in neurological and inflammatory disorders. Thus, we aimed to decipher contributions of glial connexin-43 (Cx43) in the pathophysiology of POI. METHODS: We induced POI in mice using in vivo intestinal manipulation and used glial Cx43cKO (Sox10CreERT2;Cx43fl/fl) or RiboTag (Sox10CreERT2/Rpl22HA/+) mice to evaluate Cx43-dependent signaling. Human enteric glial cultures (hEGC) and muscularis externa obtained during intestinal surgery translated findings to patients. Transcriptome analysis, immunofluorescence co-labeling, Western blots, and Cx43 hemichannel activation were used for quantitative analysis. RESULTS: Cx43 is the highest expressed connexin in enteric glia in mice and humans. Up-regulation of Cx43 occurs in various disease models linked to POI, GI surgical trauma, inflammation, immune cell activation, and enteric gliosis. In the mouse POI model, glial Cx43-deletion reduces glial reactivity, pro-inflammatory signals, upregulates host protection genes, regulates immune cell activation, and prevents enteric neuropathy. In hEGCs, interleukin (IL)-1β induction opens Cx43 and stimulates release of IL-6 and C-C motif ligand 2 (CCL2). The Cx43 peptide inhibitor, 43Gap26, inhibits glial Cx43 activation, reduces IL-6 release, and blocks upregulation of macrophage activation factors and immune cell regulation factors. Surgical intestinal trauma in patients upregulates Cx43 during inflammation and enteric gliosis in mouse POI. CONCLUSIONS: Glial Cx43 signaling promotes enteric gliosis, immune cell activation, inflammation, and enteric neuropathy in mice with potential translatability to humans after intestinal surgical trauma and mechanical stress in POI. Interventions that block glial Cx43 activation may be protective against POI development.

Animals↗
PubMed1976

[Paralytic and postoperative ileus (author's transl)].

Paralytic ileus is always a reaction of the organism to a disturbance usually due to metabolism. A treatment without elimination of the eliciting cause seems, therefore, to have little point. The efficacy of many substances given to stimulate peristalsis has not been proved. Drawing off the contents of the stomach and controlled infusion therapy, on the other hand, are important parts of the treatment, as for mechanical ileus. For the surgical emptying of the intestine, the most suitable procedure is retrograde squeezing of the intestinal contents to the stomach and aspiration through a nasal sound. Enterotomies should be avoided if at all possible. Surgical intervention for paralytic ileus is most frequently necessary in the postoperative phase, usually caused by a peritonitis with or without anastomotic failure. Differentiation from mechanical obstruction is not always possible. In the Erlangen Hospital, 233 patients were treated for postoperative ileus from 1965 to 1974. All patients with a mechanical ileus were operated on, the mortality was 17%. Of 123 patients with a paralytic ileus, 82 were operated on and 45 died. The mortality was almost equally high in patients not operated on.

Adult↗
PubMed1978

Postoperative ileus: a colonic problem?

Postoperative electromechanical activity of the gastric antrum, small bowel, right colon, and sigmoid colon was recorded in stumptail monkeys in response to retroperitoneal dissection and transient clamping of the renal pedicle. Bipolar silver electrodes and extraluminal bonded strain gauge transducers were used to record slow-wave and spike discharges and contractions of intestinal smooth muscle. After operation myoelectric activity was decreased transiently in the antrum and for only a few hours in the small bowel. Right colon contractile activity was decreased significantly for 24 hours and that of the sigmoid colon for 72 hours. Postoperative inhibition of bowel motility appears to be most profound and persistent in the colon.

Abdomen↗
PubMed1979

The effects of metoclopramide on postoperative ileus. A randomized double-blind study.

Metoclopramide or placebo was administered postoperatively in a randomized, double-blind fashion to 115 patients undergoing laparotomy. The effect of metoclopramide on postoperative adynamic ileus (PAI) was evaluated. The patients were stratified into two groups: Group A--those with laparotomy without a gastrointestinal anastomosis or ostomy procedure, and group B--those with laparotomy undergoing an anastomosis or ostomy procedure. Metoclopramide reduced nausea and emesis postoperatively. However, the only significant effect on postoperative adynamic ileus was an earlier return to tolerance of solid foods in the patients in Group A.

Adult↗
PubMed1975

[Postoperative ileus. Measurement of the changes in intragastric pressure immediately after abdominal operations (practical deductions)].

During the post-operative period, there is no intestinal paralysis, but simply a transient disorder of motility, the duration and intensity of which are different in the stomach, small intestine and colon. The asynchronism between regularisation of motor activity of the small intestine, which is almost immediate, and that of the colon, which occurs later, is responsible for the clinical picture usually noted. In the light of these new findings, the author analyses the various factors liable to modify the course of post-operative and attempts to suggest appropriate management of the immediate post-operative period.

Abdomen↗
PubMed1976

Effect of 13-Nle-motilin in postoperative ileus patients: a double-blind trial.

In this study, the effect of 13-norleucine motilin (13-Nle-M) on post-cholecystectomy ileus was assessed in 6 female patients. 13-Nle-M given by continuous i.v. infusion (0.4 mug/kg-h) on the second and third day following surgery did not influence the manifestation and duration of intestinal paralysis in comparison to 6 control patients treated with 0.9% saline. Bowel sounds, however, were more pronounced in the 13-Nle-M-group. Blood pressure and pulse rate were not influenced by the polypeptide, and no other side effects were seen, either.

Adult↗
PubMed1977

Pathophysiology of postoperative ileus.

In eight dogs, cellotomy, rubbing the small bowel, and exposing it to air suppressed the migrating bursts of action potentials and contractions that occur in the gastrointestinal tract during fasting and greatly slowed (one to three days) the gastrointestinal transit of 7-mm plastic spheres. The operation also caused a transient one-day increase in the concentration of epinephrine and a more prolonged five-day increase in the concentration and norepinephrine in arterial and venous plasma. Phentolamine mesylate and propranolol hydrochloride prevented the inhibition of the bursts of gastric action potentials brought about by operation, but these drugs did not alter the inhibition of the small intestinal action potentials or the speed of gastrointestinal transit of spheres.

Action Potentials↗