Diversion Of Pancreatic Juice Research Articles

Enhanced recovery after pancreaticoduodenectomy: A descriptive study of patient outcomes from 2010–2018 at St. Luke's medical center, Quezon city, Philippines

Objectives: The general objective is to describe outcomes of patients who were enrolled to the ERAS program and will undergo pancreaticoduodenectomy and pancreaticojejeunostomy dunking technique with total pancreatic juice diversion at St. Luke’s Medical Center, Quezon City. Specific objectives are: to show the demographic data, operative and postoperative data,the primary outcome as length-of-stay in hospital and secondary outcomes as post-operative complications (ileus and post-operative pain),readmission rate, and mortality of patients, and incidence of grade B and C pancreatic fistula of patients who were enrolled to the ERAS program and will undergo pancreaticoduodenectomy.

Incidence of Grade B and C Pancreatic Fistula Among Patients Who Underwent Pancreaticojejunostomy Dunking Technique With Total Pancreatic Juice Diversion After Pancreaticoduodenectomy at ST. Luke’s Medical Center, Quezon City, Philippines

Incidence of Grade B and C Pancreatic Fistula Among Patients Who Underwent Pancreaticojejunostomy Dunking Technique With Total Pancreatic Juice Diversion After Pancreaticoduodenectomy at ST. Luke’s Medical Center, Quezon City, Philippines

Enhanced recovery after pancreaticoduodenectomy: a descriptive study of patient outcomes from 2010-2018 at st. Luke’s medical center, quezon city, philippines

Introduction: The general objective is to describe outcomes of patients who were enrolled to the ERAS program and will undergo pancreaticoduodenectomy and pancreaticojejeunostomy dunking technique with total pancreatic juice diversion at St. Luke’s Medical Center,Quezon City.Specific objectives are:to show the demographic data, operative and postoperative data,the primary outcome as length-of-stay in hospital and secondary outcomes as post-operative complications (ileus and post-operative pain),readmission rate,and mortality of patients,and incidence of grade B and C pancreatic fistula of patients who were enrolled to the ERAS program and will undergo pancreaticoduodenectomy. Method: This is a descriptive,prospective study from 2010-2018 at St. Luke’s Medical Center,Quezon City,Philippines of patients who will undergo pancreaticoduodenectomy with pancreaticojejunostomy dunking technique with total pancreatic juice diversion and ERAS protocol of St. Luke’s Medical Center,Quezon City. The study focused on same pancreaticoduodenectomy technique done by several surgeons and anesthesiologists who practice the ERAS protocol,which was created through a collaboration of different services:Institute of Surgery,Department of Anesthesiology,Internal Medicine and Clinical Nutrition Service. Result: Seventy-eight patients underwent pancreaticoduodenectomy using the technique from January 2010 to December 2018. Analysis of the clinical,intraoperative and post-operative parameters was done.Sixty-seven(85.9%) had no fistula and 11(14.1%) had fistula.Two patients(2.6%) were classified to have clinically apparent pancreatic fistula with 2 patients having grade B fistula and none with grade C fistula.There was a trend towards shorter hospital stay in those who were enrolled in the ERAS protocol, decreased incidence of post-operative complications, none were readmitted, and there was no mortality recorded. Conclusion: Many studies have proven that ERAS can be successfully implemented in pancreaticoduodenectomy. St. Luke’s Medical Center, Quezon City, Philippines developed and applied an ERAS protocol for pancreaticoduodenectomy since 2010. In this study,the outcomes of the patients who were enrolled in the ERAS protocol safely reduce the number of total hospital stay, incidence of post-operative complications, readmission, pancreatic fistula and mortality.

Effects of biliary and pancreatic juice diversion into the ileum on gastrointestinal motility and gut hormone secretion in conscious dogs

The aim of the present study was to investigate the effects of diversion of biliary and pancreatic juices on upper gut motility and hormone secretion. We used dogs equipped with strain gauge force transducers to measure upper gut motility. Dogs were divided into 5 groups: control, sham operation, biliary diversion (BD), pancreatic juice diversion (PJD), and biliopancreatic juice diversion (BPD). Postprandial plasma concentrations of insulin, gastric inhibitory polypeptide (GIP), and peptide YY (PYY) were also measured. Occurrence and migration velocity of the migrating motor complex in the jejunum in the interdigestive state were decreased in the BD and BPD groups compared with the other 3 groups (P<.05). In the BD and BPD groups, areas of postprandial contractile curves in the upper gut were decreased, and the duration of the postprandial contractions in the proximal jejunum, which a previous study showed to correlate with gastric emptying, were less compared with the other 3 groups (P < .05). Plasma insulin levels did not differ among the 5 groups. Plasma concentrations of GIP suppressed in the PJD and BPD groups (P < .05), whereas plasma PYY level was increased in the BD group (P < .05). Bile diversion seems to inhibit interdigestive and postprandial upper gut contractions in association with an increase of plasma PYY. Pancreatic juice was considered to play a role in the secretion of GIP.

Attempt to establish a chronic model to study the influence of bile and pancreatic juice diversion on pancreas feedback regulation in conscious pigs

The diversion of pancreatic juice and bile stimulates pancreatic exocrine secretion but the mechanism behind this process is still not clear. The present study investigates the influence of long lasting (10 h) bile diversion or pancreatic juice and bile diversion on the pancreatic secretion in conscious pigs. The experiments were performed on 4 weaned piglets, which had a catheter inserted to the accessory pancreatic duct and bile duct and two cannulas to the duodenum. The depletion of bile alone or both bile and pancreatic juice (PJ) resulted in an increased preprandial pancreatic juice outflow, as compared to controls. Bile diversion increased the pancreatic response to feeding. PJ volume, protein outflow, and trypsin activity values were significantly higher in bile diverted pigs than in control pigs during the prandial and postprandial periods. While in pancreatic juice and bile diverted piglets the PJ protein outflow and trypsin activity slightly increased in response to feeding, their values were lower than those of the control piglets. In conclusion, both pancreatic juice and bile present in the small intestine play an important role in the regulation of the pancreatic juice secretion. (c) 2007 Elsevier B.V. All fights reserved. (Less)

Inhibitory effects of octreotide on luminal cholecystokinin-releasing factor, plasma cholecystokinin, and pancreatic secretion in conscious rats.

Luminal cholecystokinin-releasing factor (LCRF), purified from rat intestinal secretions, is an intraluminal regulator of cholecystokinin (CCK) secretion during bile and pancreatic juice diversion. Because the LCRF content was not influenced by intravenous administration of atropine or somatostatin, the inhibitory effect of a potent somatostatin analog octreotide on LCRF content, the plasma CCK level, and pancreatic secretion was examined. Rats were prepared with bile and pancreatic cannulae and two duodenal cannulae and with an external jugular vein cannula. After 1.5-hour basal collection, bile and pancreatic juice was diverted for 2 hours, during which octreotide was infused intravenously or into the duodenal lumen. The changes in pancreatic secretion were recorded for 2 hours, and the plasma CCK level and LCRF content 2 hours after the treatment were measured. Bile and pancreatic juice diversion significantly increased pancreatic secretion and plasma CCK and LCRF levels. Intravenous infusion of octreotide (0.2 and 0.5 nmol/kg/hour) inhibited all parameters. Intraduodenal infusion of a lower dose of octreotide (33 nmol/kg/hour) inhibited pancreatic secretion, but did not inhibit CCK release or LCRF content. The higher doses (100 and 300 nmol/kg/hour) inhibited all parameters. Intravenous and intraduodenal administrations of octreotide inhibited CCK release and LCRF content and pancreatic secretion induced by bile and pancreatic juice diversion.

Inhibitory Effect of Somatostatin on Cholecystokinin Release Is Independent of Luminal Cholecystokinin-Releasing Factor Content in Conscious Rats

Exclusion of bile-pancreatic juice from the intestine increases pancreatic secretion via cholecystokinin (CCK) release in conscious rats. Luminal CCK-releasing factor (LCRF), purified from rat intestinal secretions, is an intraluminal regulator of CCK secretion during bile-pancreatic juice diversion. Because somatostatin is a potent inhibitor of CCK release and pancreatic secretion, the inhibitory effect of somatostatin on LCRF was examined. Rats were prepared with bile and pancreatic cannulae and two duodenal cannulae and with an external jugular vein cannula. The experiments were conducted without anesthesia. After 1.5-hour basal collection of pancreatic juice with bile-pancreatic juice return, bile-pancreatic juice was diverted for 2 hours, during which time somatostatin (2, 10 nmol/kg/h) was infused intravenously. The rats were killed before and 1 and 2 hours after bile-pancreatic juice diversion. To examine the effect of luminal somatostatin, 50 or 200 nmol/kg/h of somatostatin was infused into the duodenum. The plasma CCK and luminal content of LCRF were measured by specific radioimmunoassays. Bile-pancreatic juice diversion significantly increased pancreatic secretion, plasma CCK, and LCRF levels. Intravenous infusion of somatostatin inhibited CCK release and pancreatic secretion, but not LCRF content. Luminal administration of somatostatin did not show any effect. Inhibitory effect of circulating somatostatin on CCK release and pancreatic secretion is independent of LCRF content.

PYY inhibits CCK-stimulated pancreatic secretion through the area postrema in unanesthetized rats.

Peptide YY (PYY) inhibits CCK-8-secretin-stimulated pancreatic secretion in vivo. To investigate whether CCK-8-secretin-stimulated pancreatic secretion is mediated through a vago-vagal pathway and whether PYY inhibits this pathway through the area postrema (AP), chronic pancreatic, biliary, and duodenal catheters were implanted in AP-lesioned (APX) or sham-operated rats. The effects of APX on pancreatic secretion stimulated by bethanechol, pancreatic juice diversion (PJD), or CCK-8-secretin, were tested, with and without background PYY infusion, in unanesthetized rats. APX reduced basal pancreatic secretion by 15-20% (P < 0.01). APX had no effect on bethanechol-stimulated secretion and potentiated protein secretion stimulated by PJD (396 vs. 284%) and exogenous CCK-8-secretin. In sham-operated rats, background PYY potently inhibited CCK-8-secretin-stimulated pancreatic fluid (1.8 vs. 48.2%) and protein secretion (3.7 vs. 45.8%) but potentiated fluid (52.9 vs. 43.1%) and protein (132.9 vs. 68.9%) secretion in APX rats. Our findings demonstrate that PYY inhibits CCK-8-secretin-stimulated pancreatic secretion through an AP-dependent mechanism in sham-operated rats. The AP also contributes to basal pancreatic secretion.

Oral administration of a synthetic trypsin inhibitor increases pancreatic duct function in CCK-A receptor-deficient rats.

The effects of oral administration of a synthetic trypsin inhibitor on bicarbonate secretion were examined in cholecystokinin A (CCK-A) receptor-deficient (OLETF) rats and compared with Wistar rats. Rats were fed chow containing 0.1% trypsin inhibitor for 7 days. Rats were prepared with cannulae draining bile and pancreatic juice separately and with duodenal and extrajugular vein cannulae after 3-day trypsin inhibitor ingestion. Then the animals were maintained in Bollman cages, and the experiments were conducted 4 days after surgery. After 1.5 h of basal secretion with bile-pancreatic juice return, bile-pancreatic juice was diverted for 2 h. The responses of bicarbonate secretion to bile-pancreatic juice diversion were significantly enhanced in rats treated with trypsin inhibitor compared with those given a control diet, whereas responses of fluid and protein secretion were not affected in OLETF rats. The response of protein secretion, but not those of fluid or bicarbonate secretion, was enhanced in Wistar rats by treatment with trypsin inhibitor. Carbonic anhydrase II gene expression was increased by 7-day treatment with trypsin inhibitor only in OLETF rats, and not in Wistar rats.

Diet stimulation as a synergistic factor of aggravation in a pancreatic bile duct ligation-induced rat pancreatitis model.

We evaluated the association between aggravation of pancreatitis and multiple factors enhancing pancreatic exocrine secretion using a rat model of pancreatic bile duct ligation (PBDL)-induced pancreatitis. Under fasting and non-fasting conditions, a PBDL group, a second group treated by hepatic bile duct ligation (BDL) and a third group treated by pancreatic duct ligation (PDL) were compared in terms of serum amylase (S-amylase) activity. The S-amylase activity in the PBDL group was higher than in the sham group. In the PDL group, the increase in S-amylase activity was lower than in the PBDL group. In the BDL group, no increase in S-amylase activity was observed. Diversion of pancreatic and/or bile juice in these groups resulted in no increase of S-amylase activity. Truncal vagotomy or injection of an anticholinergic drug or a cholecystokinin (CCK)1-receptor antagonist inhibited pancreatic exocrine secretion and S-amylase activity in the non-fasting PBDL group but not in the fasting PBDL group. These results suggest that retention of pancreatic juice in the pancreatic duct is necessary for the increase of S-amylase activity, and that dietary stimulation and impaired duodenal inflow of bile and pancreatic juice commonly enhance pancreatic exocrine secretion, acting synergistically as aggravating factors in pancreatitis. CCK and the vagus nerve system appears to be involved in enhancing pancreatic exocrine secretion with diet stimulation as an aggravating factor.

Acceleration of ulcer healing by cholecystokinin (CCK): role of CCK-A receptors, somatostatin, nitric oxide and sensory nerves

CCK exhibits a potent cytoprotective activity against acute gastric lesions, but its role in ulcer healing has been little examined. In this study we determined whether exogenous CCK or endogenously released CCK by camostate, an inhibitor of luminal proteases, or by the diversion of pancreatico-biliary secretion from the duodenum, could affect ulcer healing. In addition, the effects of antagonism of CCK-A receptors (by loxiglumide, LOX) or CCK-B receptors (by L-365,260), an inhibition of NO-synthase by N G-nitro- l-arginine ( l-NNA), or sensory denervation by large neurotoxic dose of capsaicin on CCK-induced ulcer healing were examined. Gastric ulcers were produced by serosal application of acetic acid and animals were sacrificed 9 days after ulcer induction. The area of ulcers and blood flow at the ulcer area were determined. Plasma levels of gastrin and CCK and luminal somatostatin were measured by RIA and mucosal biopsy samples were taken for histological evaluation and measurement of DNA synthesis. CCK given s.c. reduced dose dependently the ulcer area; the threshold dose of CCK being 1 nmol/kg and the dose inhibiting this area by 50% being 5 nmol/kg. This healing effect of CCK was accompanied by a significant increase in the GBF at ulcer margin and the rise in luminal NO production, plasma gastrin level and DNA synthesis. Concurrent treatment with LOX, completely abolished the CCK-8-induced acceleration of the ulcer healing and the rise in the GBF at the ulcer margin, whereas L-365,260 remained without any influence. Treatment with camostate or diversion of pancreatic juice that raised plasma CCK level to that observed with administration of CCK-8, also accelerated ulcer healing and this effect was also attenuated by LOX but not by L-365,260. Inhibition of NO-synthase by l-NNA significantly delayed ulcer healing and reversed the CCK-8 induced acceleration of ulcer healing, hyperemia at the ulcer margin and luminal NO release, and these effects were restored by the addition to l-NNA of l-arginine but not d-arginine. Capsaicin denervation attenuated CCK-induced ulcer healing, and the accompanying rise in the GBF at the ulcer margin and decreased plasma gastrin and luminal release of somatostatin when compared to those in rats with intact sensory nerves. Detectable signals for CCK-A and B receptor mRNAs as well as for cNOS mRNA expression were recorded by RT-PCR in the vehicle control gastric mucosa. The expression of CCK-A receptor mRNA and cNOS mRNA was significantly increased in rats treated with CCK-8 and camostate, whereas CCK-B receptor mRNA remained unaffected. We conclude that CCK accelerates ulcer healing by the mechanism involving upregulation of specific CCK-A receptors, enhancement of somatostatin release, stimulation of sensory nerves and hyperemia in the ulcer area, possibly mediated by NO.

Pancreatic hypersecretion in the jejunal-bypass rat.

We diverted bile and pancreatic juice from jejunal blind loops of different lengths in conscious rats to see if the pancreatic secretory response was dependent on the length of the jejunal blind loop. Short-term bile and pancreatic juice diversion from a short jejunal blind loop, representing only 8-10% of the total length of the small intestine, stimulated a significant increase in pancreatic exocrine secretion. Short-term bile and pancreatic juice diversion from jejunal blind loops of increasing length resulted in a progressive decrease in the pancreatic secretory response to diversion (i.e., there appears to be a length-dependent inhibition of the pancreatic secretory response to short-term bile and pancreatic juice diversion from the jejunum). Cholinergic receptor blockade with atropine eliminated this length-dependent inhibition of pancreatic exocrine secretion during short-term bile and pancreatic juice diversion. In contrast to what was observed with short-term bile and pancreatic juice diversion, there was a length-dependent increase in pancreatic secretion during long-term bile and pancreatic juice diversion. The jejunal-bypass rat model can facilitate the investigation of the intestinal mechanisms mediating feedback regulation of pancreatic exocrine secretion.

Incidence of apoptosis in the pancreas of young and old rats

We reported previously that the pancreatic protein responses to the high dose of cholecystokinin (CCK) or bile–pancreatic juice diversion were impaired in old rats of both sexes, whereas the basal secretion was comparable to that in young animals. To examine the mechanism of the attenuated response in old rats, we examined the incidence of apoptosis of the pancreatic acinar cells and the plasma CCK concentrations produced by bile–pancreatic juice diversion, which is a potent endogenous stimulator of pancreatic secretion, in young (4–8 months old) and old (25–29 months old) rats of both sexes. Apoptosis was examined by electron microscopic examination and the nick end-labeling method for detecting cells with DNA strand breaks. The plasma CCK level was determined by RIA with OAL-656 antibody. The incidence of nick end-labeling-positive cells (apoptotic index) was slightly higher in old rats of both sexes. Apoptosis coincided with the acinar cell loss in old male rats, in which apoptotic index was much greater than that in young animals. The plasma CCK levels produced by bile–pancreatic juice diversion were lower in old than in young male rats, whereas no age difference was observed in females. The basal plasma CCK levels were comparable regardless of age and sex. The pancreatic wet weights were higher in old than in young rats of both sexes. These observations suggested that although impaired CCK functions in old male rats might have some role in the increase in apoptosis in the pancreas, the increase in apoptosis could not fully explain the attenuated pancreatic response in old rats.

Involvement of endogenous cholecystokinin and somatostatin in gastroprotection induced by intraduodenal fat.

Duodenal fat such as oleate is known to influence gut functions by release of cholecystokinin (CCK), but the contribution of CCK endogenously released by duodenal fat or by diversion of pancreatic juice from the duodenum in the mechanism of mucosal integrity and gastroprotection has been little studied. This study was designed to compare the effect of CCK-8 and intraduodenal (i.d.) instillation of sodium oleate, or diversion of the pancreatic biliary secretions that are known to release CCK, on the gastric mucosal lesions induced by topical application of 100% ethanol or acidified aspirin (ASA) in rats with or without the pretreatment with a CCK-A receptor antagonist, loxiglumide, or with L-365,260 to block CCK-B receptors. In addition, the effect of suppression of prostaglandin (PG) biosynthesis by indomethacin (5 mg/kg i.p.), inhibition of nitric oxide (NO)-synthase by L-NAME (5 mg/kg i.v.), or blockade of sensory nerves by capsaicin (125 mg/kg s.c.) on the protective activity of sodium oleate was determined. Sodium oleate (50-200 mM i.d.), or diversion of pancreatic juice from the duodenum for 3 h that produced significant rise in plasma CCK levels, significantly reduced gastric lesions induced by 100% ethanol to an extent similar to that induced by exogenous CCK-8 (5 nmol/kg s.c.). The protective effect of oleate or diversion of pancreatic juice was accompanied by an increase in gastric blood flow (GBF). Both protection and accompanying hyperemia were completely abolished by blockade of CCK-A receptors with loxiglumide, whereas L-365,260, an antagonist of CCK-B receptors, had no effect. Oleate given i.d. significantly attenuated acidified ASA-induced gastric lesions and gastric secretion while increasing the luminal concentration of somatostatin. These effects were significantly reduced by loxiglumide but not by L-365,260. In contrast, CCK-8, which stimulated gastric acid secretion, failed to affect the lesions induced by acidified ASA and the decrease in the GBF produced by this ulcerogen. Indomethacin, which suppressed PG generation by approximately 90%, failed to influence the protective activity of oleate or CCK-8 against ethanol-induced lesions, whereas L-NAME, vagotomy, or sensory denervation significantly attenuated this protection and accompanying hyperemia. Addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK-8 and duodenal oleate against gastric lesions induced by ethanol or acidified ASA. We conclude that endogenous CCK released by oleate or diversion of pancreatic secretion exerts a potent gastroprotective action on the stomach involving predominantly CCK-A receptors and depending on vagal activity, and hyperemia mediated by NO and sensory nerves but unrelated to acid secretory effects and endogenous PG.

The role of CGRP and afferent nerves in the modulation of pancreatic enzyme secretion in the rat.

Stimulation of pancreatic sensory nerves by capsaicin produced secretory effects probably caused, at least in part, by the release of CGRP. In the pancreas calcitonin gene-related peptide (CGRP) has been localized in the sensory nerves, but its physiological role is unknown. This study was undertaken to compare the changes of pancreatic enzyme secretion produced by CGRP and by stimulation or destruction of sensory nerves. To stimulate sensory nerves, low doses of capsaicin (0.25-0.5 mg/kg) were given intraduodenally to the conscious rats with chronic pancreatic fistula. To inactivate sensory nerves high doses of capsaicin (100 mg/kg) were given subcutaneously 10 d before tests. For the in vitro experiments pancreatic slices and isolated pancreatic acini were prepared from intact and capsaicin-denervated rats. In conscious rats, CGRP given subcutaneously (5-10 micrograms/kg) and low doses of capsaicin given intraduodenally reduced basal pancreatic secretion. In isolated pancreatic acini, CGRP (10(-10)-10(-6) M), but not capsaicin, increased basal or secretagog-stimulated amylase release. In pancreatic slices (containing nerve fibers) capsaicin (10(-10)-10(-6) M) increased enzyme secretion, and this secretion was abolished by previous inactivation of sensory nerves by this neurotoxin. Capsaicin deactivation did not affect the secretory response of pancreatic acini to CGRP, cerulein, or urecholine. Sensory denervation by capsaicin did not change basal protein secretion, but reduced that produced by feeding or diversion of pancreatic juice to the exterior during first 2 h of the tests.

Feedback Regulation of Pancreatic Exocrine Secretion in Minipigs

Background: The mechanism behind the possible feedback regulation of pancreatic exocrine secretion is not well understood. Methods: Thirteen minipigs were prepared with fistulas to the pancreatic duct and the duodenum. Peripheral venous blood was obtained for determination of secretin and cholecystokinin (CCK) levels. Four different experiments were performed: 1) diversion and reinfusion of pancreatic juice; 2) intraduodenal infusion of NaHCO3 solution, with the same volume, bicarbonate concentration, and osmolality as the collected pancreatic secretion, and reinfusion of pancreatic juice; 3) reinfusion of pancreatic secretion for 1 h before and 2 h after a meal; and 4) diversion of pancreatic secretion and intraduodenal infusion of NaHCO3 solutions before and after a meal. Results: Reinfusing pancreatic juice significantly decreased pancreatic juice volume and bicarbonate output and slightly decreased the level of secretin in plasma. Alternating infusions of substitute NaHCO3 and pancreatic juice did not change pancreatic output of bicarbonate and protein, nor did it change the CCK and secretin levels in plasma. Replacing pancreatic juice with intraduodenal NaHCO3 infusions during a meal did not significantly modify the pancreatic secretion of bicarbonate and protein or the hormonal levels in blood. Conclusions: A negative feedback regulation of pancreatic exocrine secretion is present in starved minipigs. Duodenal acidity and plasma levels of secretin seem to be of importance, whereas duodenal enzymatic activity and the level of CCK in plasma probably are not. A postprandial negative feedback regulation through duodenal enzymatic activity and release of CCK into blood could not be shown.

Bile and pancreatic juice replacement ameliorates early ligation-induced acute pancreatitis in rats

In healthy rats, combined bile and pancreatic juice diversion from gut has a synergistic rather than additive effect on stimulation of exocrine pancreatic protein secretion. We hypothesized that exclusion of combined bile and pancreatic juice from gut exacerbates bile and pancreatic-duct ligation-induced acute pancreatitis in rats to a greater extent than exclusion of either bile or pancreatic juice alone. Bile and pancreatic juice (obtained fresh from donor rats) were replaced, separately or together, via a duodenal fistula beginning immediately before 6 hours of duct ligation. Pancreatic morphologic changes were evaluated with an acute pancreatitis histology score and morphometric quantitation of acinar-cell necrosis. Plasma amylase and cholecystokinin concentrations and pancreatic subcellular distribution of cathepsin B activity were determined. Characteristics of bile and pancreatic juice obtained from donor rats were also studied. Combined bile and pancreatic juice replacement limited the increase in acute pancreatitis histology score by 77%, acinar cell necrosis by 95%, hyperamylasemia by 77%, and hypercholecystokininemia by 99%, while preventing subcellular redistribution of cathepsin B. Amelioration of pancreatic morphologic changes was significantly greater with combined bile and pancreatic juice replacement than with replacement of either bile or pancreatic juice alone. In this experimental corollary of early gallstone-induced acute pancreatitis, combined bile and pancreatic juice exclusion from gut contributes to disease pathogenesis to a greater extent than exclusion of either bile or pancreatic juice alone.

Negative feedback regulation of pancreatic exocrine secretion in guinea pigs.

We have investigated whether hormonally mediated negative feedback mechanisms regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea pigs prepared with a tube in the proximal duodenum, pyloric ligation, and pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for as long as 4 h in fasting states failed to increase either pancreatic secretion or plasma levels of secretin or cholecystokinin (CCK). In the same animal preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in significant increases in both pancreatic secretin and plasma levels of the two hormones that were significantly suppressed by ID infusion of pancreatic juice or a combination of trypsin and chymotrypsin. In another group of guinea pigs, this significant increase in pancreatic secretion was profoundly suppressed by a rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a combination of the antiserum and loxiglumide completely abolished the pancreatic secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated pancreatic secretion and hormone release was also studied. Atropine completely suppressed the pancreatic secretion of volume flow, bicarbonate, and protein stimulated by SO, whereas neither one of the two hormone levels was affected by intravenous atropine, indicating that atropine blocks the actions of both secretin and CCK on the pancreatic exocrine secretion. It is concluded that a negative feedback regulation of exocrine pancreatic secretion is operative in the intestinal phase of pancreatic secretion in guinea pigs and that this feedback mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs, cholinergic tone plays an important modulating role in the mechanism.

Effect of chronic pancreatic juice diversion on enteroglucagon secretion and intestinal mucosal growth in dogs.

We developed a new canine model of chronic pancreatic juice diversion from duodenum to distal ileum in order to investigate the effect of pancreatic juice on the secretion of enteroglucagon, and the growth of intestinal mucosa. In seven adult mongrel dogs, the minor pancreatic duct was ligated and excised. Then, 3 cm of duodenal segment including the pancreatic duct was transformed into a small pouch which was anastomosed to the distal ileum. Butter ingestion tests were performed before and after surgery to evaluate the effect of surgery on enteroglucagon secretion. In addition, intestinal mucosal thickness was measured, using specimens taken both at the time of surgery and during autopsy at the end of the study. We observed significant hypersecretion of enteroglucagon and mucosal growth throughout the whole small intestine. However, extent or grade of mucosal growth was not related to the mucosal contact of pancreatic juice. These results suggested that chronic pancreatic juice diversion from duodenum to the distal ileum induced mucosal growth of the whole small intestine and hypersecretion of enteroglucagon may play a important role in this growth.

Vagal efferent nerve-dependent inhibitory action of pancreatic polypeptide and peptide YY in conscious rats: comparison with somatostatin

The release of pancreatic polypeptide (PP) and peptide YY (PYY) is regulated by the vagal nerve, and the inhibitory effect of these peptides on pancreatic exocrine secretion shows indirectly via a neural mechanism. To determine the role of the vagal nerve on the inhibitory action of these peptides on the pancreas, we compared the effect on the pancreatic response to bile and pancreatic juice diversion in conscious rats with and without vagotomy. We also studied this response in rats treated with capsaicin, because bile-pancreatic juice diversion is the most potent endogenous stimulation of pancreatic secretion in conscious rats. In addition, since somatostatin potently inhibits of pancreatic enzyme secretion, the effects of PP and PYY were compared with somatostatin. An intravenous infusion of 2.5 nmol/kg per h of PP and PYY significantly inhibited the pancreatic responses of bile and pancreatic juice diversion in animals with an intact vagal nerve and in those treated with capsaicin, whereas the same dose of peptides failed to inhibit pancreatic secretion in vagotomized rats. Somatostatin inhibited pancreatic secretion under all conditions tested. We concluded that the inhibitory action of PP and PYY on pancreatic secretion is fully mediated by the vagal efferent nerve although other multiple mechanisms are involved for the inhibitory action of somatostatin.