Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 19 recordsLinked to original sources

PubMed1992

Cholecystokinin inhibits DNA alkylation induced by N-nitrosobis (2-oxopropyl)amine (BOP) in hamster pancreas.

Cholecystokinin (CCK) inhibits pancreatic cancer but not hepatic tumor induction by N-nitrosobis (2-oxopropyl) amine (BOP) in hamsters when administered with or shortly before BOP. In this study, we evaluated the capability of sulfated CCK-8 to inhibit DNA alkylation in the hamster pancreas. We examined the pattern of O6-methylguanine (G6-Me) and N7-methylguanine (G7-Me) in pancreatic ductal, acinar and liver tissues from Syrian hamsters treated with a single dose of BOP (20 mg/kg s.c.) and with five s.c. injections of CCK-8 (200 pM/kg, 30 min apart). The first CCK injection was given either 90 min before, or together, or 3 h after POP administration. The amount of G6-Me in liver DNA did not differ significantly. We observed a decrease of G7-Me in the liver of the group treated with CCK together with POP as compared to POP alone (P less than 0.005). Lower amounts of G6-Me were found in ductal preparations (P less than 0.01) of the animals treated with CCK before POP as compared to POP alone. CCK also modified the pattern of alkylation in the acinar tissue, but without a clear relationship with the timing of administration. The results suggest that the inhibitory effect of CCK-8 on pancreatic carcinogenicity of BOP could be related to its capability to modify DNA alkylation by yet unknown mechanisms.

Alkylation↗

PubMed1992

Effect of meal composition and sham feeding on duodenojejunal motility in humans.

The disruptive effect of meals of different fat content and caloric value and of sham feeding on the interdigestive migrating motor complex (IDMMC) was studied in eight healthy subjects using an ambulatory recording system that allowed continuous monitoring of small bowel motility for three consecutive days. The durations of fed pattern were not significantly different between meals of 800 kcal/50% fat, 400 kcal/50% fat, and 800 kcal/25% fat, but were significantly longer compared to IDMMC cycle length and sham feeding. The latter two were not significantly different. On a separate day, five subjects consumed a meal of 400 kcal/9% fat and a second one of 800 kcal/50% fat. The duration of the fed pattern following the high fat meal was significantly longer than the low fat one. Sham feeding significantly increased plasma concentrations of gastrin and neurotensin (NT), but did not affect those of cholecystokinin (CCK), insulin, and peptide YY (PYY). The various variables of the IDMMC were not different during the two nights of the study, and velocity of migration of phase III during the first day and both nights was similar. We conclude that the duration of the fed pattern depends, in part, on the composition of the meal. Sham feeding, resulting in an increase in both plasma gastrin and NT concentrations, does not disrupt the IDMMC. When using thin probes, IDMMC is stable during prolonged recording.

Adult↗

PubMed1992

Effect of duodenal switch procedure on gastric acid production, intragastric pH, gastric emptying, and gastrointestinal hormones.

The duodenal switch operation preserves the pylorus and the proximal 3 to 7 cm of duodenum in continuity with the stomach while diverting pancreaticobiliary secretions. We compared it with the Roux-en-Y without vagotomy or antrectomy in 12 dogs with innervated gastric pouches. Acid secretion was inhibited between tests using ranitidine in the Roux-en-Y group only, but two of the six dogs still developed stomal ulcers and the remainder showed stomal hyperemia. This may be due to a significant increase in gastric acid output after Roux-en-Y, but gastric emptying and plasma gastrin, cholecystokinin, secretin, gastric inhibitory polypeptide, peptide YY, and neurotensin were similar after both procedures. In 12 patients and a further 6 dogs, the duodenal switch caused no significant change in the intragastric pH environment as assessed by intragastric pH monitoring. The duodenal switch is a suitable procedure for pancreaticobiliary diversion.

Anastomosis, Roux-en-Y↗

PubMed1992

Neuropeptide release from the isolated, perfused, lower esophageal sphincter region of the rabbit and the effect of vasoactive intestinal peptide on the sphincter.

BACKGROUND: The aim was to evaluate the isolated, vascularly perfused, lower esophageal sphincter (LES) as a model for investigating the functional role of neuropeptides such as vasoactive intestinal peptide (VIP). METHODS: At laparotomy the LES was removed along with the distal esophagus, stomach, and left gastric artery and vein. The LES area, isolated from the body of the stomach by a custom-made clamp, was perfused with oxygenated Krebs-Ringer bicarbonate solution (pH 7.4, 38 degrees C) via the left gastric artery. The LES pressure was monitored continuously with a custom-made Dent sleeve catheter. LES pressure and release of neuropeptides were investigated after carbachol and VIP were administered alone or in combination. VIP, calcitonin gene-related peptide (CGRP), and somatostatin were measured in the venous perfusate collected from the left gastric vein. RESULTS: LES tone and contraction frequency were similarly increased by 10 and 100 nmol/L carbachol (increment, 4.0 +/- 0.26 mm Hg with 10 nmol/L carbachol; p less than 0.0003). Perfusion with 10 nmol/L VIP decreased basal tone and completely abolished the contraction induced by 100 nmol/L carbachol. VIP, CGRP, and somatostatin were released from the LES in response to 10 nmol/L carbachol (VIP rose from 55 +/- 13 to 179 +/- 24 pmol/L, CGRP, from 114 +/- 30 to 239 +/- 33 pmol/L, and somatostatin from 15 +/- 2 to 27 +/- 4 pmol/L; all p less than 0.001). CONCLUSIONS: These findings support a role for VIP in the inhibitory reflex of the LES but suggest that other neuropeptides may also be involved. The isolated, perfused LES provides a new tool for investigating neuropeptide interactions.

Animals↗

PubMed1991

Adaptive increase in peptide YY and enteroglucagon after proctocolectomy and pelvic ileal reservoir construction.

Functional results improve with time after proctocolectomy and pelvic ileal reservoir construction. We hypothesized that adaptive increases of circulating and tissue levels of the gut hormones peptide YY (PYY) and enteroglucagon may contribute to this improvement by slowing small bowel transit and increasing small bowel absorption. The specific aim of this study was to measure plasma and ileal mucosal concentrations of PYY and enteroglucagon in dogs 1 year after proctocolectomy and ileal reservoir-anal anastomosis. In the ileal reservoir dogs, postprandial PYY levels reached 238 +/- 31 pmol/liter compared with 93 +/- 33 pmol/liter in sham operated controls (P less than 0.001). Postprandial plasma enteroglucagon levels reached 199 +/- 53 pmol/liter in reservoir animals and 52 +/- 4 pmol/liter in controls (P less than 0.05). Tissue levels of PYY in the mucosa of the ileal reservoirs were 419 +/- 43 pmol/g compared with 133 +/- 23 pmol/g in normal terminal ileum (P less than 0.0001). Enteroglucagon levels were also elevated in reservoir mucosa (193 +/- 21 pmol/g vs. 113 +/- 9 pmol/g in controls, P less than 0.05). These data demonstrate that postprandial and tissue levels of PYY and enteroglucagon increase in dogs 1 year after construction of ileal reservoirs. The adaptive increase in PYY would slow small bowel transit and the increase in enteroglucagon would promote mucosal growth, each contributing to the improved functional results.

Adaptation, Physiological↗

PubMed1991

Distribution and immunocytochemical colocalization of peptide YY and enteroglucagon in endocrine cells of the rabbit colon.

Peptide YY (PYY) is 36 amino acid peptide hormone present in high concentrations in the colon where it is colocalized with enteroglucagon in L cells. A selective release of PYY and enteroglucagon from the rabbit colon has been described, raising the question of the exact localization of the two hormones in the rabbit colon. We have therefore examined the distribution of PYY and enteroglucagon as well as somatostatin in the rabbit colon using RIA and electron microscopic immunocytochemistry. PYY and enteroglucagon were present in high concentrations in the colorectal mucosa with peak concentrations in the left colon (PYY 544 +/- 87 pmol/g, enteroglucagon 152 +/- 10 pmol/g). Electron microscopic examination of the colonic mucosa demonstrated a large population (65%) of EC cells, a moderate population (30%) of L cells, and a small population (5%) of D cells. By immunogold labeling serotonin was localized to EC cells, PYY and enteroglucagon to L cells, and somatostatin to the D cell. Double immunogold labeling revealed PYY and enteroglucagon in all L cells examined (93 cells). A majority of the secretory granules (83%) were labeled by both PYY and glucagon antibodies, whereas a significant portion of granules (15%) was labeled by the PYY antibodies alone. The results demonstrate that L cells are the sole source of PYY and enteroglucagon in the rabbit colon and that L cells contain different populations of secretory granules. The existence of different secretory granules in L cells may explain the selective release of PYY and enteroglucagon observed in the rabbit colon.

Animals↗

PubMed1991

Short-chain fatty acid release of peptide YY in the isolated rabbit distal colon.

Short-chain fatty acids (SCFAs) form the major ionic fraction of stool, provide the major metabolic substrate for colonic epithelium, and promote mucosal ion transport. Despite this prominent role of SCFAs in metabolism of the colon, their effect on colonic endocrine cell function has not been studied. Consequently, we hypothesized that SCFAs might modulate release of peptide YY (PYY) from colonic type-L endocrine cells. The specific aims of this study were to measure release of PYY from the isolated perfused rabbit distal colon stimulated by intraluminal infusion of 0.9% saline, acetate (10 mM), acetoacetate (10 mM), n-butyrate (1, 3.3, 10, 100 mM), and pyruvate (10 mM). PYY levels were measured by radioimmunoassay in the venous effluent of the rabbit colon. All four SCFAs (10 mM) caused at least a twofold increase in integrated release of PYY from the isolated perfused rabbit colon. Graded concentrations of n-butyrate caused a stepwise release of PYY. This study suggests that SCFAs may modulate the release of colonic PYY in rabbits.

Acetates↗

PubMed1990

Significance of gastric endocrine tumor and age-related gut peptide alterations in Mastomys.

The Mastomys (Praomys natalensis) species are a unique natural model in which the bioactivity of gastric carcinoids may be studied. Several investigators have previously demonstrated that these tumors contain large amounts of histamine. In this study we investigated the presence of peptides associated with the neoplasm. The levels and location of gastrin, gastric inhibitory peptide (GIP), neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), glucagon, bombesin, vasoactive intestinal peptide (VIP) and somatostatin (SRIF) were investigated by radioimmunoassay and immunocytochemistry. In addition the distribution of these peptides were evaluated in the gastrointestinal tract of young and old animals to investigate possible age-related changes. PYY and enteroglucagon (EG) were significantly (P less than 0.001) elevated in both tumor tissue (676 +/- 152, 551 +/- 164 pmol/g) and plasma (620 +/- 160, 500 +/- 147 pmol/l) of tumor-bearing animals. Immunocytochemistry revealed PYY- and EG-like immunoreactivity in 20-30% of tumor cells. A significant decrease (P less than 0.05) in bombesin was noted in older animals, but no changes in gastric tissue content of PYY or EG could be detected between young and old animals. Gastrin was not detected in tumors and there were no significant changes in tissue or plasma levels with age. Small bowel concentrations of VIP and PYY were higher in the older mastomys (P less than 0.05). In contrast, colonic levels of bombesin, VIP, somatostatin and PYY were significantly lower (P less than 0.05) in older mastomys compared with young. The age-related changes in several peptides may reflect an adaptive response to acid hypersecretion. The multi-hormonal character of these neoplasms suggests that these tumors develop from a pluripotential stem cell.

Age Factors↗

PubMed1990

Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist.

Acute edematous pancreatitis follows excessive cholinergic stimulation in patients exposed to anticholinesterase-containing insecticides. We describe the role of cholecystokinin and the benefits of cholecystokinin receptor blockade in this form of pancreatitis. A cholinergic mimetic (carbachol) was administered to rats weighing 300 to 350 g and produced a form of edematous pancreatitis that mimics that seen in humans. Animals received carbachol intraperitoneally, either alone (250 micrograms/kg of body weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of body weight) and were killed 4 hours later. Carbachol administration resulted in a 19% increase in pancreatic weight, a fourfold increase in serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma cholecystokinin levels, however, were not altered. Devazepide administered prior to cholinergic hyperstimulation blocked pancreatic weight increase and reduced elevations in serum amylase levels twofold and lipase levels fourfold. Although cholecystokinin levels are not elevated in this model of pancreatitis, blockade of even low, background concentrations of this regulatory peptide is beneficial.

Acute Disease↗

PubMed1990

Intra-ocular transplantation of carcinoid tumours from mastomys and humans.

Carcinoid tumours from man and Mastomys (Praomys) natalensis produce a variety of peptide hormones. The study of these peptide-secreting tumours has been difficult because of the small amount of tissue available and because of limitations with present cell culture systems. The aim of this study was to establish an experimental model where carcinoid tumours could be maintained and their hormone secretion studied. The intra-ocular transplantation technique was chosen for its simplicity and high rate of success. Gastric carcinoid tumours from mastomys (n = 4) and human carcinoids (n = 2) (one bronchial and one ileal) were transplanted to the anterior eye chamber of Sprague-Dawley rats. Pieces of fresh tumour tissue were injected into the anterior eye chamber of rats and allowed to grow for 4-8 weeks. Rats transplanted with human tissue were immunosuppressed by daily injections with cyclosporin A (20 mg/kg). Eye chambers were inspected regularly and plasma from transplanted rats was collected for assay of peptide YY (PYY) and glucagon. Vascularization of transplants occurred within 1-2 days after transplantation in 70-80 per cent of all experiments. Microscopic analysis of transplants demonstrated a rich supply of blood vessels to tumour cells which contained characteristic neurosecretory granules. Transplanted rats had significantly (P less than 0.05) elevated levels of PYY (44-165 pmol/l) and glucagon (67-162 pmol/l) in plasma as compared with sham-operated rats (PYY 28-40 pmol/l, glucagon 33-40 pmol/l), indicating that hormone secretion by tumour cells in oculo was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Pepsinogen release and acid secretion from human and guinea pig gastric mucosa compromised by hypoxia, endotoxin, or critical illness.

Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p less than 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p less than 0.05). Endotoxic and air-gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 +/- 1701 U/ml. The gastric juice of H2-blocked convalescing surgical patients (n = 20) contained 315 +/- 101 U/ml (p less than 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p less than 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients.

Animals↗

PubMed1990

Effects of cholecystokinin and cholinergic receptor blockade on guinea pig pepsinogen secretion.

Although cholecystokinin (CCK) has been reported to stimulate pepsinogen secretion, this action has been poorly characterized. To assess the ability of CCK to regulate mammalian pepsinogen secretion, guinea pig fundic mucosa was incubated in Ussing chambers with CCK-8, carbamylcholine, and pentagastrin, and with cholinergic and CCK antagonists. CCK-8 stimulated pepsinogen secretion at 10(-10) M, with an ED50 of 10(-9) M and maximally (26-fold over basal) at 10(-8) M. Carbachol stimulated pepsinogen and acid secretion with an ED50 of 3 x 10(-7) M and maximally at 10(-6) M. Pentagastrin (10(-9) M-10(-6) M) did not affect acid or pepsinogen secretion, whereas gastrin-I (10(-6) M) stimulated acid secretion slightly but did not alter pepsinogen secretion. L364, 718 (10(-5) M), a specific CCK peripheral receptor antagonist, abolished all pepsigogic effects of 3 x 10(-9) M CCK-8 without altering basal acid or pepsinogen secretion or mucosal electric characteristics. L364,718-treated tissues unresponsive to CCK-8 nevertheless secreted pepsinogen and acid in response to 3 x 10(-7) M carbachol identically to control carbachol-treated preparations. Atropine (10(-5) M) blocked the response to 3 x 10(-7) M carbachol without inhibiting 10(-9) M CCK stimulation. These results support a specific receptor-mediated role for cholecystokinin in the physiologic regulation of guinea pig pepsinogen secretion.

Animals↗

PubMed1990

A novel micromethod for pancreatic acinar secretion. Time course of CCK stimulation and its inhibition by L-364,718.

Dispersed acini have proven to be particularly valuable in the study of pancreatic enzyme secretion. Complex time course studies or experiments requiring large numbers of replicates have proven difficult, however, with currently available techniques. Using a custom-designed incubation chamber, a miniaturized incubation method has been devised, which allows for continuous oxygenation of acini in 96-well microtiter plates and rapid separation of medium from acini by vacuum filtration. The filtrates from individual wells are collected into the wells of a second microtiter plate for pancreatic enzyme measurement. Using the above method, the dose response and time course of cholecystokinin (CCK-8)-stimulated amylase secretion was investigated. During a 1-h incubation, unstimulated amylase secretion was 4.1 +/- 0.3% of total acini content. Response to CCK was very sensitive, being detected at 10(-13) M (p less than 0.05), half-maximal at 10(-11) M CCK (14.0 +/- 0.6%, p less than 0.001) and maximal at 10(-9) M CCK (24.8 +/- 1.0%, p less than 0.001). In the time course experiments, an increase in amylase secretion was detected by 2.5 min and continued to increase steadily to a plateau at 40 min, with both submaximal (10(-11) M) and maximal (10(-9) M) CCK concentrations. The potent and specific CCK-receptor antagonist, L-364,718, caused a dose-dependent decrease in CCK-stimulated amylase secretion, with a half-maximal effect at 10(-10) M. The receptor antagonist, L-364,718, at 10(-8) M completely abolished CCK-stimulated amylase secretion. This microtechnique provides a simple, reliable, and reproducible method for the study of dispersed pancreatic acini.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

PubMed1989

A micromethod for the assay of cellular secretory physiology: application to rabbit parietal cells.

A micromethod for investigating secretory physiology in isolated cells was evaluated. The method utilized a specially designed polycarbonate incubation chamber to provide constant oxygenation to cells incubating in a 96-well microtiter plate. Cells were rapidly separated from media by vacuum filtration. Isolated parietal cells were utilized to demonstrate the versatility of the method for assay of intracellular accumulation of [14C]-aminopyrine, secretion of intrinsic factor into the medium, and assay of intracellular cAMP. Histamine stimulated the uptake of [14C]aminopyrine and intrinsic factor secretion in a sustained and linear fashion. At the end of the 2-h period uptake of aminopyrine and secretion of intrinsic factor were increased 17- and 5-fold, respectively. This response to histamine was accompanied by a rapid and sustained 3-fold rise in intracellular cyclic AMP. In contrast, carbamylcholine caused a transient increase in [14C]aminopyrine accumulation and intrinsic factor secretion which was most pronounced during the first 10 min and had almost ceased by 30 min. Carbamylcholine had no effect on intracellular cAMP levels. This new method, which can handle 400 replicates using parietal cells from the fundic mucosa of a single rabbit, is suitable for studying the time course of intracellular events which accompany general secretory processes.

Aminopyrine↗

PubMed1989

Cholecystokinin augmentation of 'surgical' pancreatitis. Benefits of receptor blockade.

The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.

Acute Disease↗

PubMed1989

Intramural distribution of immunoreactive vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin in the oesophago-gastro-pyloric region of the human gut.

The intramural distribution of vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin was studied in the oesophago-gastro-pyloric region of the human gut. At each of 21 sampling sites encompassing this entire area, the gut wall was separated into mucosa, submucosa and muscularis externa, and extracted for radioimmunoassay. VIP levels in the mucosa were very high in the proximal oesophagus (1231 +/- 174 pmol/g, mean +/- SEM) and showed varied, but generally decreasing concentrations towards the stomach, followed by a clear-cut increase across the pyloric canal (distal antrum: 73 +/- 16 pmol/g, proximal duodenum: 366 +/- 62 pmol/g); consistent levels were found in submucosa and muscle (200-400 pmol/g) at most sites, the stomach again showing lower concentrations. By contrast, substance P was present in small amounts as far as the proximal stomach, but sharply increased across the pyloric canal, especially in mucosa and submucosa (distal antrum: 20 +/- 6.5 and 5.5 +/- 1.3 pmol/g; proximal duodenum: 62 +/- 8.5 and 34 +/- 11 pmol/g, respectively). Somatostatin concentrations were very low in the mucosa of the oesophagus and stepwise increased in the cardiac, mid-gastric and pyloric mucosa (cardia: 224 +/- 72 pmol/g; distal antrum: 513 +/- 152 pmol/g; proximal duodenum: 1013 +/- 113 pmol/g); concentrations in the submucosa and muscularis were generally low, with the exception of antrum and duodenum. Mammalian bombesin was comparatively well represented throughout the oesophageal muscularis (5-8 pmol/g), but most abundant in the stomach in all layers (oxyntic mucosa: 24 +/- 2.7 pmol/g; submucosa: 20 +/- 5.7 pmol/g; muscle: 28 +/- 5.0 pmol/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Regional differences in concentrations of regulatory peptides in human colon mucosal biopsy.

The study was undertaken to examine regional differences in the concentrations of five regulatory peptides in the human colonic mucosa. Biopsies were obtained during routine colonoscopy from 33 patients whose colonic mucosa was macroscopically and histologically normal. Regulatory peptides were extracted, and measured by specific radioimmunoassays. Concentrations of three peptides that are present predominantly in endocrine cells within colonic mucosa increased significantly towards the rectum: Mean concentrations of peptide YY, enteroglucagon, and somatostatin were about three times greater in the rectum than in the cecum. However, concentrations of two peptides that are present in mucosal nerve fibers diminished significantly towards the rectum: Mean rectal concentrations of vasoactive intestinal peptide and peptide histidine methionine were both about 0.6 of mean cecal concentrations. Concentrations of all five peptides were lower in biopsies taken from colonic polyps than in normal colonic mucosa. Regional differences in colonic mucosal concentrations of regulatory peptides probably reflect differences in the physiological functions of different parts of the colon.

Adolescent↗

PubMed1989

Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction?

We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.

Animals↗