vasoactive-intestinal-peptide and Postoperative-Complications

Our aim was to explore unknown changes in neurotransmission with vasoactive intestinal peptide (VIP) and Substance P (Sub P) during postoperative ileus (POI).. Contractile activity of rat circular jejunal muscle strips was studied in five groups (n = 6/group): Naïve controls, sham controls 12 h and 3 days after laparotomy, and rats 12 h, 3 days after induction of POI. Dose-responses to VIP (10(-10) -10(-7) M), Sub P (3 × 10(-10) -3 × 10(-7) M), and electrical field stimulation (EFS, to study endogenous release of neurotransmitters) were studied with different antagonists. Intestinal transit, inflammatory cells and immunoreactivity for VIP and Sub P were investigated in the bowel wall and cellular Finkel osteo sarcoma expression was determined in vagal afferent and efferent nuclei of the brainstem.. Postoperative ileus characterized by delayed intestinal transit and intramural inflammation was associated with an increased inhibitory effect of VIP on contractile activity. A biphasic impact was observed for Sub P with a decrease in its excitatory potential on contractility at 12 h, followed by a later increase 3 days postoperatively. Inhibitory response to EFS was increased, whereas the excitatory response decreased in ileus animals. VIP expression was increased in all postoperative animals while only animals 3 days after ileus induction showed increased Sub P expression in the myenteric plexus. These changes were associated with an activation of afferent but not efferent vagal nuclei in the brain stem.. Specific, time-dependent changes in peptidergic neurotransmission with VIP and Sub P occur during POI that are associated with vagal afferent activation, but are independent of the activation of efferent vagal pathways.

Topics: Animals; Electric Stimulation; Gastrointestinal Agents; Gastrointestinal Motility; Ileus; Jejunum; Male; Myenteric Plexus; Postoperative Complications; Rats; Rats, Sprague-Dawley; Substance P; Vasoactive Intestinal Peptide

Skin biopsies from patients with reflex sympathetic dystrophy were immunostained using a variety of antisera. An incidental finding with S100 staining was the presence of numerous Langerhans cells in the epidermis. All patients had significant pain at the time of biopsy, and all had symptoms refractory to treatment. The potential implications of this finding are discussed.

Topics: Adult; Aged; Biopsy; Calcitonin Gene-Related Peptide; Causalgia; Female; Fluorescent Antibody Technique; Hand; Humans; Langerhans Cells; Middle Aged; Nerve Fibers; Nerve Regeneration; Postoperative Complications; Reflex Sympathetic Dystrophy; S100 Proteins; Skin; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

1. Vasoactive intestinal polypeptide (VIP) is an inhibitory neurotransmitter in the enteric nervous system. We investigated the role of VIP1/PACAP receptors in postoperative ileus in rats. 2. Different degrees of inhibition of the gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy or laparotomy plus mechanical stimulation of the gut. 3. The transit after skin incision or laparotomy was not altered by the VIP1/PACAP receptor antagonist Ac-His1,D-Phe2, K15, R16, VIP(3-7), GRF(8-27)-NH2 nor by the VIP1/PACAP receptor agonist K15, R16, VIP(1-7), GRF(8-27)-NH2 and the VIP2/PACAP receptor agonist RO 25-1553 (5 microg kg(-1)). 4. However, the transit after laparotomy plus mechanical stimulation was significantly enhanced by the VIP1/PACAP receptor antagonist, whereas it was further inhibited by the VIP1/PACAP receptor agonist. The combination of the VIP1/PACAP receptor agonist and antagonist counteracted the effect of both drugs alone. The VIP2/PACAP receptor agonist did not alter the effect of the VIP1/PACAP receptor antagonist. 5. The combination of the VIP1/PACAP receptor antagonist plus the nitric oxide (NO) synthase inhibitor L-nitroarginine had no effect on the transit after laparotomy plus mechanical stimulation, while the transit after skin incision was significantly decreased. 6. These findings suggest the involvement of VIP1/PACAP receptors, next to NO, in the pathogenesis of postoperative ileus. However, the combination of the VIP1/PACAP antagonist and the NO synthase inhibitor abolished the beneficial effect of each drug alone, suggesting the need for one of the inhibitory neurotransmitters to enable normal gastrointestinal transit.

Topics: Animals; Dose-Response Relationship, Drug; Gastrointestinal Transit; Intestinal Obstruction; Male; Nitric Oxide; Postoperative Complications; Rats; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; Vasoactive Intestinal Peptide

Recent studies suggest that the intestinal polypeptides substance P (SP) and vasoactive intestinal polypeptide (VIP) play a role in the bowel inflammatory processes. The aim of this study was to evaluate the distribution of SP and VIP immunoreactivities in the ileal pouch of the patients with ulcerative colitis (UC). Thirty-six patients underwent clinical evaluation, endoscopy, and histological examinations. Samples were taken from normal ileum (N = 9), ileum of UC patients (N = 9), normal ileal pouch (N = 9) and pouchitis (N = 9). SP- and VIP-containing nerve fibers were visualized in sections processed for immunofluorescence microscopy. The number and intensity of SP and VIP immunoreactivities were subjected to quantitative scoring. On samples from all groups lamina propria contained fibers showing bright immunofluorescence for SP and VIP. The number and intensity of SP immunoreactive nerve fibers were markedly increased in pouchitis as compared to normal pouch (P < 0.005), to ileum of UC patients (P < 0.001), and to normal ileum (P < 0.05). The number and intensity of VIP-immunoreactive nerve fibers in the lamina propria were markedly increased in pouchitis patients and in those having a normal pouch as compared to pooled values of ileum of UC patients and normal ileum (P < 0.05). The results suggest that SP, which may play a role in mediating inflammatory processes, is increased in pouchitis and that VIP, which may contribute to the regulation of intestinal motility, is increased in the pouch.

Topics: Adult; Aged; Colitis, Ulcerative; Female; Humans; Ileum; Immunohistochemistry; Inflammation; Male; Middle Aged; Nerve Fibers; Postoperative Complications; Proctocolectomy, Restorative; Substance P; Vasoactive Intestinal Peptide

Recent studies suggest that substance P (SP), vasoactive intestinal polypeptide (VIP), and mast cells play a role in inflammatory processes of the bowel. The aim of this study was to evaluate the distribution of SP and VIP immunoreactivities and to count mast cells in the ileal pouch of patients, who had pouchitis after restorative proctocolectomy performed for treatment of ulcerative colitis (UC), and to compare the findings in the same patients after a follow-up period. Nine patients with pouchitis underwent clinical evaluation, endoscopy of the pouch, and histological examination, which were repeated after the follow-up period of 14 months on average. The number and intensity of SP- and VIP-immunoreactive nerve fibers were visualized by immunofluorescence microscopy and subjected to quantitative scoring, and the number of mast cells per unit area was counted. The results were compared to the histological findings and the clinical status. Lamina propria contained fibers showing bright immunofluorescence for SP and VIP. The mean fluorescence intensity score of SP-immunoreactive nerve fibers in the lamina propria remained similar after the follow-up period (2.99 +/- 0.79 and 2.06 +/- 0.82, NS). SP-immunoreactive innervation correlated with the grade of acute (R2 = 0.5396, P = 0.0242) and chronic inflammation (R2 = 0.4561, P = 0.0459), while SP and VIP immunoreactivity, mast cell count, and histological changes did not correlate with the clinical status. The present study demonstrates an increase in the density of SP-immunoreactive nerve fibers in inflamed ileal pouch mucosa of clinically asymptomatic pouchitis patients. These results raise the possibility of therapeutic interference of SP-related processes in treatment of pouchitis.

Topics: Adult; Biopsy; Cell Count; Colitis, Ulcerative; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Humans; Ileum; Immunohistochemistry; Inflammation; Male; Mast Cells; Middle Aged; Nerve Fibers; Postoperative Complications; Proctocolectomy, Restorative; Substance P; Vasoactive Intestinal Peptide

A possible involvement of perivascular vasodilatory neuropeptides in subarachnoid haemorrhage (SAH) has been evaluated in man by measuring the levels of calcitonin gene related peptide (CGRP)-, substance P (SP)- and vasoactive intestinal peptide (VIP)-like immunoreactivity (LI) in the cranial venous outflow and in CSF in 34 patients admitted to the hospital after an acute SAH. After operation with aneurysm clipping and nimodipine treatment, blood samples were taken from the external jugular vein (EJV) or cerebrospinal fluid (CSF) and analysed for neuropeptide levels with specific radioimmuno assays (RIA) during the postoperative course. The degree of vasoconstriction in the patients was monitored with Doppler ultrasound recordings bilaterally from the middle cerebral (MCA) and internal carotid arteries (ICA) following the EJV blood sampling every second day. The mean value of all CGRP-LI measurements in EJV during the entire course of SAH (n = 20) revealed a significantly higher level as compared to controls. The highest CGRP-LI levels were found in patients with the highest velocity index values (vasospasm). The relationship Vmean MCA/Vmean ICA was used as an index of vasoconstriction. In patients with MCA aneurysms (n = 10), a significant correlation (r = 0.65, p < 0.05) was found between the vasospasm index and CGRP-LI levels. There were no changes observed in the SP- and VIP-LI levels. Alterations in cerebrovascular tone induced by changing arterial CO2 tension or lowering of blood pressure (ketanserin infusion test) did not alter the levels of the perivascular peptides in the EJV. In addition, CGRP-, SP-, VIP- and neuropeptide Y (NPY)-LI were analysed in CSF in the post-operative course after subarachnoid haemorrhage (SAH) in 14 patients. The CSF VIP-LI was lower in SAH than in control (p < 0.05). The CGRP-LI level was measurable in SAH CSF but not in CSF of controls. In individual patients with marked vasoconstriction increased levels of CGRP-LI (up to 14 pmol/L) and NPY-LI (up to 232 pmol/L) were observed. The results of this study are in support of our hypothesis that there is an involvement of the sensory peptide CGRP in a dynamic reflex aimed at counterbalancing vasoconstriction in SAH.

Topics: Adult; Aged; Aneurysm, Ruptured; Blood-Brain Barrier; Brain; Calcitonin Gene-Related Peptide; Female; Homeostasis; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Jugular Veins; Male; Middle Aged; Postoperative Complications; Subarachnoid Hemorrhage; Substance P; Ultrasonography, Doppler, Transcranial; Vasoactive Intestinal Peptide; Vasoconstriction; Vasodilation

Octreotide, a somatostatin analogue that inhibits the release of most gut peptides, hastens the resolution of experimental postoperative ileus, suggesting that gut peptides mediate this process. We studied the role of two gut peptides involved in the control of normal gut motility, vasoactive intestinal peptide (VIP), and substance P (SP), in the initiation and maintenance of postoperative small bowel ileus in rats by preoperative administration of VIP and SP receptor antagonists, (VIP-ra and SP-ra). Thirty male Sprague-Dawley rats (300-350 g) underwent laparotomy. One half underwent placement of a duodenal catheter for transit studies while the other half had serosal electrodes placed on the proximal jejunum for myoelectric recordings. Six days later, animals were separated into three treatment groups of five each. Control animals were pretreated with ip saline, while the others received either VIP-ra or SP-ra prior to standardized laparotomy. Following abdominal closure, [Na51]CrO4 was injected into the duodenum and the animals were sacrificed 25 min later. The small bowel was then excised and divided into 10 equal segments. Small bowel transit was calculated as the geometric center of [Na51]CrO4 distribution. The interval until the return of migrating myoelectric complexes (MMCs) was determined in animals with intestinal electrodes. VIP-ra-treated rats demonstrated a 67% improvement in the geometric center of radiolabel relative to controls and SP-ra-treated rats had a 23% improvement (3.67 +/- 0.06 VIP-ra vs 2.69 +/- 0.09 SP-ra vs 2.20 +/- 0.09 control, P < 0.01). MMCs returned 180 +/- 17 min in controls vs 99 +/- 14 min in VIP-ra-treated rats (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Intestinal Obstruction; Male; Myoelectric Complex, Migrating; Neurokinin-1 Receptor Antagonists; Postoperative Complications; Rats; Rats, Sprague-Dawley; Receptors, Vasoactive Intestinal Peptide; Substance P; Vasoactive Intestinal Peptide

The hypothesis was that postoperative ileus might be caused by a disturbed balance between the motor-stimulating hormones, motilin and substance P, and the motor-inhibitory hormone, vasoactive intestinal polypeptide, and that octreotide might prevent this disturbance and so ameliorate the ileus. In 15 conscious dogs with chronic gastrointestinal electrodes, electrical activity was recorded and blood was drawn for radioimmunoassay of motilin, substance P, and vasoactive intestinal peptide (VIP) during fasting and after a liquid meal. Ileus was then induced by celiotomy and intestinal abrasion. During and after operation, five dogs received 154 mM NaCl only, five dogs octreotide, 0.19 micrograms/kg/hr, and five octreotide, 0.83 micrograms/kg/hr. Plasma levels of motilin, substance P, and VIP were changed little by operation, but cyclical increases in plasma motilin, which occurred preoperatively during phase III of the interdigestive myoelectric complex, were completely abolished postoperatively during ileus, as was the complex itself. Octreotide ameliorated the ileus and restored the cyclic increases in motilin found in health, nor did it alter plasma substance P and VIP. In conclusion, octreotide ameliorates postoperative ileus, but it does not do so by increasing plasma motilin or substance P or decreasing plasma VIP.

Topics: Animals; Dogs; Eating; Female; Intestinal Obstruction; Motilin; Octreotide; Postoperative Complications; Substance P; Vasoactive Intestinal Peptide

The significance of dysplastic features in the surgical pullthrough segment of bowel in patients with Hirschsprung's disease (HD) has not yet been clarified. The aim of this study was to evaluate prospectively the ganglionated proximal bowel in 26 patients with HD (January 1988 through January 1991). The significance of dysplastic features and their influence on post operative outcome were evaluated by means of a newly devised histological scoring system based on the morphological features. Functional outcome was assessed clinically at follow-up interview. Comparison was with control specimens from 22 patients undergoing unrelated bowel surgery and a further 5 patients with neuronal intestinal dysplasia (NID). Results indicated a wide spectrum of histologically identified dysplastic features in patients with NID, the ganglionated bowel of HD and controls. Although individual abnormal features were noted in the control group, significant degrees of dysplasia were absent. The overall degree of dysplasia was less striking than that observed in NID and in the 5 patients in whom NID co-existed with HD. Dysplasia of the ENS in residual bowel could be correlated with postoperative dysfunction in 4 out of 5 patients (80%) with HD and features of co-existing NID. In addition, milder symptoms were noted in 50% of patients having a borderline score (5-6/12). This study emphasizes the relationship between clinical obstructive symptoms and a high degree of dysplasia within the ENS. A histological grading system is of value in evaluating the spectrum of abnormal findings and prospectively identifying those with functional significance in patients with NID co-existing with HD.

Topics: Acetylcholinesterase; Child; Child, Preschool; Female; Follow-Up Studies; Hirschsprung Disease; Humans; Immunoenzyme Techniques; Infant; Intestines; Male; Myenteric Plexus; Neuroglia; Neurons; Phosphopyruvate Hydratase; Postoperative Complications; Prognosis; Prospective Studies; Submucous Plexus; Vasoactive Intestinal Peptide

After colectomy, continent ileal reservoirs are an accepted alternative to conventional ileostomy for patients with ulcerative colitis. To assess the effect of these reservoirs on digestive function, circulating and morphologic gut endocrine responses were measured in patients with a continent ileostomy or with a pelvic pouch and compared to patients with conventional ileostomy, with active ulcerative colitis and healthy controls. Eight subjects were studied in each group. Basal and postprandial plasma gastrin, enteroglucagon, neurotensin, vasoactive intestinal polypeptide, insulin, pancreatic glucagon, and pancreatic polypeptide in both groups with ileal reservoirs were equivalent to controls. Basal plasma motilin and postprandial plasma gastric inhibitory polypeptide were raised in ileal reservoir patients, but similar changes also occurred in ulcerative colitis patients and those with conventional ileostomy. In one half of patients, cell populations of enteroglucagon, peptide YY, and neurotensin were decreased in pouch mucosa that corresponded with the presence of mucosal inflammation. On the other hand, with pouch inflammation vasoactive intestinal polypeptide immunoreactive nerves were increased and a proportion of the fibres were moderately coarsened. Mucosal concentrations of vasoactive intestinal polypeptide did not, however, exceed that of controls. After an ileal reservoir sufficient reserve remains for gut hormone release into the circulation, suggesting compensation for the presence of a reservoir and the absence of a colon; circulating hormone changes do occur but are consequent upon previous ulcerative colitis. Reservoirs may show neuromorphologic alterations that appear to be related to mucosal inflammation.

Topics: Adult; Colitis, Ulcerative; Eating; Female; Gastrointestinal Hormones; Humans; Ileitis; Ileostomy; Ileum; Male; Middle Aged; Neurotensin; Pancreatic Hormones; Postoperative Complications; Vasoactive Intestinal Peptide

In a preliminary study the effect of an aperitif of a stable fat emulsion on symptoms, gastric emptying of a hypertonic glucose meal and associated release of insulin, neurotensin, enteroglucagon, gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP) was evaluated in 9 patients with postprandial gastrointestinal discomfort after vagotomy. In each patient gastric emptying of the glucose meal was measured twice: 20 min after intake of distilled water and after fat emulsion. On both occasions neurotensin, enteroglucagon and GIP rose significantly from fasting values. In contrast to distilled water, the fat emulsion was able to significantly activate the release of the hormones before ingestion of the glucose meal. All the patients had a rapid emptying of the glucose meal after distilled water and they experienced symptoms that corresponded with the nature of their spontaneous symptoms after ordinary meals. The fat emulsion reduced the early emptying of the meal and relieved the symptoms of the dumping patients, whereas gastric emptying and symptoms were variable in the patients with diarrhoea and other postvagotomy symptoms. The intake of an aperitif of soya bean oil seems to be an effective treatment only in patients with the dumping syndrome.

Topics: Adult; Aged; Blood Glucose; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Neurotensin; Plant Oils; Postoperative Complications; Soybean Oil; Vagotomy; Vasoactive Intestinal Peptide

This study evaluated the effect of gastric bypass on the glucose, insulin, vasoactive intestinal peptide (VIP), neurotensin, and motilin response to orally administered glucose in eight morbidly obese patients before and after operation. Preoperatively, all eight patients remained asymptomatic during an oral glucose tolerance test, which showed glucose intolerance and hyperinsulinism. Plasma VIP, neurotensin, and motilin remained below detectable levels for the entire test. At three months following gastric bypass (21% weight loss), all eight patients became acutely ill during a repeated oral glucose tolerance test and had the following symptoms: facial flushing (eight patients), palpitations (eight patients), nausea (seven patients), abdominal fullness (seven patients), pallor (four patients), diaphoresis (two patients), vomiting (two patients), and diarrhea (two patients). Significant release of neurotensin occurred in seven patients while three patients had release of VIP, further implicating these two peptides as part of the pathophysiologic spectrum of the "dumping syndrome."

Topics: Adult; Blood Glucose; Dumping Syndrome; Female; Glucose Tolerance Test; Humans; Jejunum; Male; Neurotensin; Obesity; Postoperative Complications; Stomach; Vasoactive Intestinal Peptide