Infusion Of Secretin Research Articles

Cardiovascular effects of secretin infusion in man

Cardiovascular effects of secretin infusion in man

The early diagnosis of gastrinoma.

Despite the increasing awareness of gastrinoma and its lethal peptic ulcer sequelae, the diagnosis is often initially missed or made as a terminal event. The authors screened all patients with peptic ulcer symptoms serious enough to warrant hospital admission or those associated with diarrhea, nephrolithiasis, hypercalcemia, or pituitary abnormality. In a one-year period (1979-1980) nine (of 14 suspected) new gastrinoma patients were identified using a sensitive and specific gastrin radioimmunoassay in combination with provocative tests including IV secretin, calcium, and food. Conventional upper GI series, CAT scan, arteriography, and endoscopy provided no additional information other than to confirm the presence of ulcer disease. Basal plasma gastrin levels were more than 200 pmol L-1 in only three of the nine (normal fasting plasma gastrin levels are less than 25 pmol L-1). Three patients presented with acute ulcer perforation, and the diagnosis of gastrinoma was suspected because of multiple ulcers and pancreatic masses. In three other patients, previous duodenal ulcer surgery had failed. One patient with dyspepsia, high basal plasma gastrin, negative secretin and calcium infusion studies, and a positive meal test was diagnosed as having G-cell hyperplasia; this was confirmed by biopsy and antral gastrin extraction. Antrectomy alone resulted in cure. In all patients tested, a positive calcium infusion or secretin bolus (greater than 100% rise over basal) strongly suggested the diagnosis of gastrinoma, which was confirmed at surgery. In the acute perforations, initial management with omental patch and cimetidine therapy allowed survival of two patients, while emergency total gastrectomy in the third resulted in death due to esophagojejunal leak. Elective patients were treated with cimetidine initially for at least two weeks before total gastrectomy. In this group there were no operative mortalities, and postoperative morbidity was minimal. This series illustrates three important points: (1) careful screening of an ulcer population using gastrin radioimmunoassay and provocative tests has enabled a high yield of gastrinomas while conventional investigations are of minimal values; (2) a high index of suspicion in appropriate cases is necessary; and (3) total gastrectomy performed under elective circumstances is safe and allows the patients to resume a normal and healthy life without the sequelae of aggressive peptic ulceration or daily drug administration.

Serum pancreatic enzyme levels in cystic fibrosis heterozygotes after secretin and cholecystokinin infusion.

. The response of serum trypsinogen and amylase to pancreatic stimulation was examined in heterozygotes for cystic fibrosis (CF) and normal subjects. Serum trypsinogen rose significantly from the baseline in CF heterozygotes at 30 (p<0.001), 60 (p<0.01) and 120 minutes (p<0.05), but at only 30 minutes (p<0.02) in normal subjects. The mean serum trypsinogen level at 30 and 60 minutes was significantly higher in CF heterozygotes than normal subjects (both p<0.05). There was no change in total serum α-amylase levels. These results suggest that CF heterozygotes show either partially obstructed pancreatic ducts or pancreatic acini which secrete trypsinogen at an increased rate when stimulated.

Calcium and parathyroid hormone behaviour after exogenous secretin infusion in man.

The response of serum calcium, PTH, CT and gastrin to an infusion of secretin (3 CU/kg/h) over a period of 90 min was studied in ten healthy males and two female patients with hypoparathyroidism. In the healthy males serum calcium, after a transient fall, significantly increased at 45 min after the onset of the infusion (P less than 0.001). Serum iPTH rose significantly within 5 min whereas serum CT and gastrin concentrations did not change. The two hypoparathyroid patients did not show any variations in either serum iPTH or calcium. These findings suggest that infusion of pharmacological doses of secretin into normal subjects modifies serum calcium, and that this change is due to PTH release.

Modulation of pancreatic polypeptide secretion by pancreatico-biliary juice.

The only apparent physiological action of pancreatic polypeptide (PP) in man is the inhibition of pancreatic and biliary secretions. The purpose of this study was to test the hypothesis that there exists a feedback loop whereby pancreatico- biliary secretions modulate and/or stimulate PP release into the circulation. We first compared the plasma PP response to an iv infusion of secretin (2 U/kg bolus and 0.125 U/kg infusion over 30 min), with and without simultaneous aspiration and perfusion of the duodenum with normal saline, in 10 healthy subjects. Constant washout of the duodenum with normal saline (10 ml/min) reduced the integrated PP response (IPPR) to iv secretin from 5.7 ± 1.2 to 2.2 ± 0.5 ng-min/ml. In a separate set of experiments in 6 healthy subjects, intraduodenal perfusion of pancreatico-biliary juice did not reduce the plasma PP response to secretin stimulation (IPPR = 5.9 ± 0.9 ng-min/ml). Perfusion of the duodenum with pancreatico-biliary juice alone stimulated the release of PP into the c...

The effect of atropine and duct decompression on the evolution of Diazinon-induced acute canine pancreatitis.

Three groups of eight dogs each were studied to evaluate the early evolution of the hyperamylasemia, hyperlipasemia, and acinar cell pathology at the light and electron microscopic levels during acute Diazinon-induced pancreatitis. Two more groups of five dogs each were evaluated for the effects of cholinergic receptor blockade with atropine and ductal decompression on the evolution of serum enzyme changes and acinar cell pathology. Group I dogs received a secretin infusion of 2 units/kg/hr, and a Diazinon infusion of 75 mg/kg, and demonstrated significant increases in serum amylase and lipase at one, two and three hours. Light microscopy revealed acinar cell vacuolization and progressive interstitial edema. Electron microscopy revealed the formation of large intracytoplasmic vacuoles filled with flocculent material, the fusion of these vacuoles with basolateral membrane, and the formation of interstitial edema. In both group II dogs (that received secretin alone) and Group III dogs (that received atropine, 200 micrograms/kg IV prior to secretin and Diazinon), the serum enzyme levels and histologic results were normal. In group IV dogs, pancreatic duct cannulation to prevent hypertension prevented the hyperamylasemia and hyperlipasemia, but not the acinar cell vacuolization and interstitial edema. This model for acute interstitial pancreatitis is apparently cholinergic-receptor mediated, the serum enzyme elevations are due primarily to ductal hypertension, and the acinar cell pathology is primarily due to cholinergic stimulation and occurs independent of ductal hypertension.

Plasma secretion and pancreatic secretion in response to liver extract meal with varied pH and exogenous secretin in the dog.

1. In dogs with chronic gastric and pancreatic fistulas, a liver extract meal adjusted to various pH levels ranging from 7.0 to 2.0, was introduced into the stomach and the increments in plasma secretin levels were correlated with the pH of the liver extract meal and pancreatic bicarbonate outputs. 2. The pH threshold for both bicarbonate secretion and secretin release was found to be about 4.5. With a stepwise decrease in the pH of the meal below pH 4.5, there were stepwise increments in the plasma secretin concentrations and pancreatic bicarbonate outputs. 3. Exogenous secretin, given in graded doses ranging from 0.03 to 2.0 clinical unit/kg per hr, increased the plasma secretin concentrations and bicarbonate secretion in a dose-dependent fashion. 4. These results indicate that the pH threshold for release of endogenous secretin is 4.5 and suggests that, at pH levels below 4.5, pancreatic bicarbonate secretion depends upon the duodenal acid load and is linearly correlated to an increment in plasma secretin concentrations. 5. It is concluded that endogenous secretin is a major determinant of pancreatic bicarbonate secretion after a meal. 6. Pancreatic protein secretion by intragastric liver extract meal was greatly increased both in experiments with liver extract meal, pH 4.0 or below, and I.V. infusion of secretin at a dose of 0.12 u./kg per hr. It is questioned, however, whether this effect of secretin is physiological.

Permeability of intestinal capillaries: effects of fat absorption and gastrointestinal hormones.

The purpose of this study was to determine whether the postprandial increase of intestinal lymphatic protein flux is due to an increased capillary permeability. Intestinal lymph flow and lymph (L) and plasma (P) protein concentrations were measured at various venous pressures under control conditions, after cream feeding, and during intraluminal perfusion with a bile-oleic acid solution. The osmotic reflection coefficient (sigma d), a measure of capillary permeability that is independent of surface area, was estimated under all conditions, assuming sigma d = 1 - L/P at high capillary filtration rates. The results acquired indicate that cream feeding and intraluminal perfusion with bile-oleic acid significantly increases intestinal capillary permeability. Pretreatment with indomethacin and antihistamines did not alter the permeability increase induced by intraluminal bile-oleic acid. Intra-arterial infusion of cholecystokinin and secretin did not increase intestinal capillary permeability. These studies indicate that the postprandial increase in intestinal lymphatic protein flux is due at least in part, to an increase in capillary permeability. Cholecystokinin, secretin, histamine, and prostaglandins do not appear to mediate the increased intestinal capillary permeability during fat absorption.

Pancreatic synthetic rates: a new test of pancreatic function.

Synthesis of pancreatic enzymes was measured in 7 patients with chronic pancreatitis and 10 patients with no pancreatic disease, on the basis of the incorporation of 75Se-methionine into pancreatic exocrine proteins. Two of the patients with chronic pancreatitis had normal exocrine function. Pancreatic secretion was stimulated by intravenous infusion of secretin (1 clinical unit x kg-1 x h-1) and cholecystokinin (1 Ivy dog unit x kg-1 x h-1). 75Se-methionine (3.0 microCi x kg-1) was added to the infusion. Synthetic rates were significantly greater in all the patients with chronic pancreatitis, including the two individuals with normal responses to stimulation with secretin and cholecystokinin. Studies of synthetic rates may therefore be able to confirm the diagnosis of chronic pancreatitis before exocrine insufficiency becomes manifest.

Pancreatic Secretory Response to Sham Feeding in Humans

We studied the pancreatic secretory response to sham feeding alone or during secretin infusion with and without administration of atropine in 10 human subjects. The magnitude of the response to sham feeding was compared to the response to cholecystokinin octapeptide. Sham feeding alone did not significantly increase pancreatic bicarbonate or amylase secretion above basal values. During a background secretin infusion, there was a significant increase of bicarbonate and amylase output (p less than 0.05) during sham feeding. The amylase response was approximately 50% of the maximal response to cholecystokinin octapeptide. In the tests with atropine and secretin, sham feeding still caused a significant increment in amylase and bicarbonate output. We conclude that (1) the pancreatic response to sham feeding is not clearly demonstrated without a background of secretin; (2) during secretin infusion sham feeding is a potent stimulant of pancreatic enzyme secretion, and (3) atropine had no significant effect on the pancreatic response to sham feeding under the conditions of this study.

Secretin enhances [14C]erythritol clearance in unanesthetized dogs.

To determine the effect of secretin infusion on clearance of inert markers into bile, unanesthetized dogs fitted with Thomas cannulas received continuous infusions of [14C]erythritol and [3H]inulin throughout study. Taurocholic acid administered sequentially at 9.0, 20.0, and 40.0 mumol/min enhanced [14C]erythritol clearance, and GIH secretin (3 units/min) administered along with TCA (40.0 mumol/min) increased [14C]erythritol clearance from 4.9 +/- 1.2 ml/10 min to 6.8 +/- 1.3 ml/10 min (P less than 0.001), but simultaneously measured [3H]inulin clearance was unaltered. Secretin alone also increased [14C]erythritol clearance but did not alter [3H]inulin clearance. The increase in [14C]erythritol clearance per unit increase in bile flow was less during secretin infusion than TCA. Thus, secretin increases [14C]erythritol transport through restricted channels, probably distal to the canaliculi. [14C]Erythritol may not be an accurate marker for canalicular bile flow in dogs during secretin infusion.

Effect of hormones on cyclic AMP in dog pancreatic tissue and secretion

Secretin and cholecystokinin (CCK-PZ) were administered intravenously in graded doses to live anesthetized dogs. Pancreatic secretion and tissue biopsies were analyzed for cyclic AMP content. Both secretin and CCK-PZ caused an output of cyclic AMP into pancreatic secretion, secretin being a more potent stimulant than CCK-PZ. The concentration of cyclic AMP in the pancreatic juice increased with increasing doses of secretin but not with CCK-PZ. Tissue cyclic AMP content remained unchanged during infusion of either secretin or CCK-PZ. Infusion of aminophylline with secretin did not potentiate the action of secretin. It is concluded that synthesis of cyclic AMP in the dog pancreas is stimulated by both secretin and CCK-PZ and that the newly synthesized cyclic AMP is rapidly secreted into pancreatic juice, resulting in a steady content of tissue cyclic AMP.

Does basal cholinergic activity potentiate exogenous secretin for stimulation of pancreatic bicarbonate output in dogs?

In conscious dogs with gastric and pancreatic Thomas fistulas, we studied the effect of atropine sulfate (20 micrograms kg-1 h-1 intravenously) on bicarbonate output basally and in response to intravenous infusion of synthetic secretin (62.5, 125, 250, 500, 1,000 and 2,000 ng kg-1 h-1). We analyzed the data in an attempt to determine whether basal cholinergic activity potentiates the pancreatic bicarbonate response to secretin. Assuming that atropine suppresses all basal cholinergic activity, C (= bicarbonate response to basal cholinergic activity alone) was calculated by subtracting basal pancreatic bicarbonate output with atropine from that without atropine, S (= response to secretin alone) was calculated by subtracting basal pancreatic bicarbonate output with atropine from that in response to secretin with atropine. SwC was defined as the response to secretin acting simultaneously with (w) basal cholinergic activity and was calculated by subtracting basal pancreatic bicarbonate output with atropine from the response to secretin without atropine. If SwC was significantly greater than S + C (= sum of effects of stimulus alone and basal cholinergic activity alone) potentiation between basal cholinergic activity and secretin was assumed to exist. C was 30 +/- 9 mumol 15 min-1 for bicarbonate output. SwC of bicarbonate output was significantly (p less than 0.05) greater than S + C in response to the four lowest doses (62.5-500 ng kg-1 h-1) of secretin. We conclude that potentiation exists between basal cholinergic activity and low doses of exogenous secretin. Thus, basal cholinergic activity is an important modulator of pancreatic bicarbonate response to secretin.

The effect of secretin on gastric H+ and pepsin secretion and on urinary electrolyte excretion in man.

After an initial 40-min period of gastric suction, the gastric juice was collected for 12 30-min periods from 8 healthy young male students. During the first hour 30-min periods saline alone was infused, whereafter secretin in a dose of 0.05 CU/kg and h was given in the middle four 30-min periods and in a dose of 0.25 CU/kg and h for the final four 30-min periods. Urine was collected in three 2-h portions corresponding to each change of infusion procedure, and blood for determination of plasma secretin by a radioimmunoassay procedure was drawn at hourly intervals. Plasma secretin was unaltered both during the saline infusion and during the infusion of secretin in a dose of 0.05 CU/kg and h but rose during the infusion of 0.25 CU/kg and h. Compared with the mean 30-min output in the initial saline control period, gastrin pepsin secretion rose significantly in the third 30-min period, and gastric H+ output fell significantly in the fourth 30-min period of infusion of secretin in a dose of 0.05 CU/kg and h. During the higher secretin dose gastric output could not be evaluated owing to duodenogastric reflux. Urinary sodium excretion increased only during the infusion of secretin in a dose of 0.25 CU/kg and h, whereas secretin showed no effect on the urinary outputs of water, potassium, and solutes. The results of the present study indicate that secretin may play a physiological role in the regulation of gastric H+ and pepsin secretions, whereas its diuretic effect probably is a pharmacological effect only.

Effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion, release of gastrin, and pancreatic polypeptide in the anesthetized dog.

The short-term effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion and release of gastrin and pancreatic polypeptide (PP) were studied in 18 anesthetized dogs. Together with an intravenous infusion of secretin (250 ng/kg/hr) bombesin (500 ng/kg/hr) was given before and after truncal vagotomy, antrectomy, and sham operation (N = 6 dogs per group). Peak incremental pancreatic protein output in response to bombesin was about 2-3 times higher before than after the different surgical procedures (tachyphylaxis). Neither truncal vagotomy nor antrectomy significantly altered the pancreatic protein response to bombesin when compared with sham operation. Bombesin produced a mean 1-hr increase over basal of 196 pM for gastrin, which was abolished by antrectomy but not appreciably affected by truncal vagotomy and sham operation. The mean 1-hr increment (207 pM) for PP in response to bombesin was not changed by truncal vagotomy, antrectomy, and sham operation. This study shows in the anesthetized dog that exogenous bombesin stimulates release of PP as well as gastrin; that the release of gastrin by bombesin is not vagally dependent; that neither truncal vagotomy nor antrectomy alter the release of PP by bombesin; and that the action of bombesin on pancreatic protein secretion does not depend on release of gastrin or on intact vagal nerves.

Effect of intravenous ethanol on pancreatic secretion in the conscious rat

To study whether the secretory state of the in vivo pancreas affects its response to ethanol, we administered ethanol intravenously to conscious rats in the presence and absence of exogenous secretin. In the absence of secretin when pancreatic secretion was maintained at basal levels, intravenous ethanol produced a significant stimulation of the flow rate, bicarbonate concentration, and protein concentration. This response persisted despite elimination of gastric acid production by infusion of the H2 receptor antagonist cimetidine. In contrast, intravenous ethanol inhibited the flow rate and bicarbonate concentration when pancreatic secretion was augmented by the infusion of GIH secretin. Thus, the rat pancreas responds differently to intravenous ethanol in the basal and secretin-stimulated states. These results may account for the lack of agreement regarding the pancreatic effects of systemic ethanol.

Effect of sodium oleate on plasma secretin concentration and pancreatic secretion in dog

The effects of sodium oleate and triglyceride infused into the duodenum of dogs with chronic pancreatic fistulas on pancreatic secretion and plasma immunoreactive secretin were investigated. The responses were compared with those following intravenous secretin infusions. Oleate markedly increased pancreatic water and bicarbonate secretion in a dose-related fashion, and these increases were accompanied by a small, but significant rise in the level of circulating immunoreactive secretin. No change in pancreatic secretion or in plasma secretin level was observed by the administration of triglyceride. Comparison of the bicarbonate response after oleate infusion with that after secretin administration suggests that the pancreatic stimulatory effect of intraduodenal sodium oleate is mediated to a major extent by the release of endogenous secretin.

Effects of anorexigenic peptide on gastric and pancreatic secretion.

1. Gastric and pancreatic secretion as well as serum gastrin an insulin levels have been measured after sham-feeding, real feeding or exogenous hormonal stimulation in conscious dogs receiving (pyro) Glu-His-Gly, an appetite depressing peptide (AP). 2. Sham-feeding produced a marked increase in gastric acid and pepsin outputs accompanied by an elevation of serum gastrin and insulin concentrations. AP infusion before and after sham-feeding reduced the peak gastric secretion and suppressed gastrin and insulin responses to sham-feeding. 3. Liver extract meal administered into the stomach resulted in an increase in gastric acid and serum gastrin and insulin levels. AP inhibited acid response to liver extract without affecting serum hormonal levels. Pentagastrin stimulation produced similar acid secretion to that obtained with liver extract and AP infusion also inhibited this secretion. 4. Secretin infusion or feeding a meat meal produced a similar rate of pancreatic bicarbonate secretion in dogs with chronic pancreatic fistula. AP infusion inhibited the bicarbonate response to feeding or secretin without affecting serum gastrin or insulin levels. 5. This study demonstrates that pyro-Glo-His-Gly suppresses serum hormonal and gastric secretory response to cephalic stimulation and reduces gastrin and pancreatic secretory responses to ordinary feeding or exogenous hormonal stimuli.

Secretin is an enterogastrone in the dog.

To determine the physiological significance of secretin on gastric secretion, effects of normal rabbit serum (control) and rabbit antisecretin serum (anti-S) on meat meal-stimulated gastric secretion of acid and pepsin from vagally innervated fundic pouches were studied in four dogs with gastric fistulas. The intravenous administration of control serum did not affect the postprandial rise in plasma secretin concentration, whereas intravenous anti-S virtually eliminated the circulating plasma secretin. Both plasma gastrin concentration and acid output following intravenous anti-S were significantly greater than those following intravenous control serum. However, pepsin outputs in the two groups of experiments were not significantly different. In the same dogs in the fasting state, during intravenous infusion of secretin in doses of 0.06 and 0.125 U . kg-1 . h-1, the acid output stimulated by intravenous human synthetic gastrin in a dose of 0.25 micrograms . kg-1 . h-1 was significantly less than that during intravenous saline. The studies indicate that secretin in a physiological dose can inhibit postprandial release of gastrin and gastric secretion of acid, and thus secretin is an enterogastrone in the dog.

Management and long-term results in patients with two-thirds gastrectomy and stomal ulcer

In 67 patients with two-thirds gastrectomy and endoscopically proven stomal ulcer, serum gastrin levels were measured under basal conditions and after intravenous infusion of bombesin (15 ng/kg/ min), calcium (4 mg/kg/hour) and secretin (2 units/ kg). All patients underwent medical or surgical therapy. The long-term results were evaluated according to the Visick grading system (average follow-up, 3.1 years).