Human exocrine pancreatic secretion changes associated with age.

A retrospective study of data from 2352 secretin tests has been studied. Age-related changes in the structure and function of the gastrointestinal tract have been the subject of many publications. There is a consensus that basal and stimulated gastric secretion declines with age. Studies of pancreatic secretion in the elderly are scattered in the old literature and are rather controversial. Previously published data from this laboratory indicated that age and sex have little or no influence upon the secretory responses of the human pancreas to a standard dose of secretin. Almost 20 years have passed since this publication. The present report is a retrospective analysis of the observations gathered over this period.

Effects of intravenous ethanol on basal bile-pancreatic secretion in nonalcoholic and alcohol-fed rats.

In nonalcoholic (NA) and alcohol-fed rats (AF), intravenous-ethanol-induced percentage changes in bile-pancreatic-secretion (BPS) were evaluated, with and without gastric juice diversion (GJD) and with and without BPS duodenal recirculation (DR). Even with GJD, ethanol elicited a slight increase in BPS. These changes were greater in AF animals even when performed without GJD. When intravenous ethanol was given under conditions of GJD and DR, there were marked differences between the NA and AF animals in the ethanol-elicited post-plateau percentage changes of BPS. NA animals evidenced no significant difference from controls. But in the AF rats, ethanol triggered a marked and significant increase of flow, protein concentration, and output that became progressively greater in successive collection periods. It is postulated that without DR, and the resulting lack of negative duodeno-pancreatic reflexes (DPR), there occurs a change in reactivity to intravenous ethanol of the hypothalamic-bulbar nuclei (HBN) and in the mechanisms that modulate the flow of cholinergic impulses through the intrapancreatic ganglia (IPG). The postulated consequence is predominance (slight in NA rats receiving intravenous ethanol, greater in AF rats) in discharge of positive impulses from HBN and flowing unimpeded through the IPG to the "pancreon" units. In the NA animal with DR, ethanol may enhance BPS values, but in the AF rats, impairment of the negative DPR elicited by chronic alcohol intoxication might, after an acute intravenous ethanol injection, favor the discharge of positive impulses from the HBN flowing unimpeded through the IPG. In the AF rats also, ethanol would activate the nonnicotinic receptors of the neurons of the "antral," "duodenal," and "celiac" autonomic brains.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute pancreatitis in a patient treated for alcoholic hepatitis. The hypothesis of supranormal ecbolic stimulation of the pancreon.

A 33-yr-old white woman treated for alcoholic hepatitis developed acute pancreatitis during her hospital stay. At autopsy, two major pathological processes were found: alcoholic cirrhosis and chronic pancreatitis. In both, there was evidence of an acute episode, i.e., acute alcoholic hepatitis and acute hemorrhagic pancreatitis superimposed on the chronic alcoholic lesions. The sequence of events would indicate that the acute pancreatic pathology was precipitated by supranormal ecbolic stimulation of the acinar segment of the "pancreon" units, triggered as a result of a high protein and fat diet.

The pancreas and oxygen consumption (Part 2). Steroids do not modify resting pancreatic oxygen consumption in dogs: a preliminary report.

In order to evaluate the effect of methylprednisolone sodium succinate (MPSS) on the alteration of pancreatic oxygen consumption (VO2) in hypovolemic shock, MPSS was administered to four normal canines and three hypovolemic animals. All were treated according to the protocol used in the initial report. (The Pancreas and Oxygen Consumption 1: Pancreatic Oxygen Consumption in Normo- and Hypovolemic Dogs.) All seven underwent a splenectomy at the beginning of the experiment. Pancreatic VO2, obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas, was equal to the product of regional blood flow, Q, determined electromagnetically on the gastroduodenal (GDA) and splenic (SA) arteries, times O2 extraction, (a-v)O2; O2 content (in mL%) was measured in the femoral artery (RFA), in the splenic (SV) and superior pancreaticoduodenal (SPDV) veins. Similar determinations were carried out on the right hind limb that served as a control. Recordings were made for 4 h in both groups, the first hour determinations (five in all) serving as reference values. Methylprednisolone did not appear to alter pancreatic VO2, which showed a significant increasing trend from + 77% 1 h after MPSS had been given, to + 98% 3 h later (vs + 56 and + 92%, respectively, in the control group). As in the control group, these increases were owing to augmented O2 extraction by the pancreas. No significant change was noted between the head and tail of the pancreas. In the hind limb, VO2 increased significantly the first 2 h and differed from control VO2 at the end of the first hour only.

Caerulein stimulates pancreatic secretory response in conscious newborn rats.

UNLABELLED: The aim of our study was to measure age-dependent, caerulein-stimulated pancreatic enzyme secretion of conscious CFY suckling rats without pancreatic duct cannulation. Pancreatic secretory response was expressed as the decrease in specific enzyme (trypsin, amylase) activity compared to saline-injected control. The study was performed in three phases. In 10-d-old conscious newborn rats, single 1 and 3 micrograms/kg sc doses of caerulein induced significant decreases in specific trypsin (42 and 47%) and amylase (34 and 33%) activity 15 min after the caerulein injection; the same doses injected at 0 and 30 min evoked a similar decrease 90 min after the first injection. The 0.5 microgram/kg dose was ineffective. In 10-d-old anesthetized rats, the 90-min-decrease in total pancreatic trypsin activity, induced by graded doses (1,3,10, and 30 micrograms/kg) of caerulein, was compared to the 90-min output of trypsin in their bile-pancreatic juice. Each of the applied doses induced significant change in the total trypsin activity both in the pancreas (-33-57%) and juice (+21 +/- 49%) and its decrease in the gland corresponded quantitatively well (r = 0.52; p less than 0.01) to the increase in the simultaneous 90-min trypsin output. The age- and dose-dependent pancreatic response of 3-, 5-, 10-, and 20-d-old conscious rats was investigated under the effect of 1,3,10, and 30 micrograms/kg sc doses of caerulein injected at 0 and 30 min. In 3-d-old rats, the 10 and 30 micrograms/kg and in 20-d-old rats, the 1 and 3 micrograms/kg doses were effective, whereas in 5- and 10-d-old rats each caerulein dose applied evoked a significant decrease in pancreatic-specific trypsin activity. CONCLUSION: The pancreas of newborn rats is in vivo less sensitive to caerulein between postnatal d 3 and 10 than in already weaned rats.

The pancreas and oxygen consumption. 1. Pancreatic oxygen consumption in normo- and hypovolemic dogs.

Pancreatic oxygen consumption (VO2) was studied in hypovolemic shock: 4 dogs served as controls and 4 others were kept at 50 mm Hg of mean arterial blood pressure. All 8 were studied for a period of 3 h. Pancreatic VO2 was obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas both equal to the product of regional blood flow times O2 extraction. Regional blood flows were measured electromagnetically on the gastroduodenal (GDA) and the splenic (SA) arteries, whereas O2 extraction was derived from total hemoglobin (THb) and oxygen saturation of hemoglobin (%O2 Hb) determined on the right femoral artery (RFA), the superior pancreaticoduodenal (SPDV), and splenic (SV) veins. A splenectomy was performed in all 8 dogs. Controls showed a significantly elevated pancreatic VO2 from the first hour of observation on (+56% after 1 h, +92% after 3), whereas pancreatic VO2 remained strictly unchanged throughout shock (+2% and +6%, at one and 3 h, respectively), despite significant increases in O2 extraction. These findings give support to the deleterious effects of hypovolemia to the pancreas and that pancreatic O2 extraction indicates metabolic damage to be less severe than observed in experimental bile-trypsin-induced acute pancreatitis.

Pure pancreatic juice in humans: orange-lemon-juice-induced secretory effects. Comparative analysis with a regular meal, sorbitol, acidified peptone broth and secretin.

The secretory effect elicited by the ingestion of 100 ml of orange-lemon juice (O.-L.J.) was studied on pure pancreatic juice obtained from a catheter placed in the human Wirsung duct at surgery. These changes were compared with those evoked by a regular meal (R.M.), the ingestion of a Sorbitol solution (S.S.), the intragastric infusion of an acidified peptone broth (A.P.B.) and an i.v. single injection of secretin (Boots, 1.0 U/kg). The O.-L.J. induced purer pancreatic secretion response (flow, bicarbonate and enzyme output) than that triggered by the R.M., S.S. and A.P.B. The O.-L.J. evoked peak values, were observed earlier (60 min) than with a R.M. (90 min) ingestion. The 120-min-cumulative values confirmed these findings and disclosed that O.-L.J. elicits a rate of secretion and bicarbonate output closely similar to that of an i.v. secretin injection and amylase response greater than that evoked by this hormone. Thus, O.-L.J. ingestion proved to be an unexpected powerful stimulus of exocrine pancreatic secretion.

Steroids do not alter pancreatic blood supply in hypovolemic dogs: implications on steroid action in acute pancreatitis.

A recent report from our laboratory showed that pancreatic inflammation induced by hypovolemic shock can be explained to some extent by spoliation in pancreatic perfusion as revealed by electromagnetic flow determinations on the gastroduodenal artery (GDA). On the other hand, when given early in the course of hypovolemic shock, methylprednisolone sodium succinate (MPSS) alleviated pancreatic inflammation as evidenced by gross and histological findings. Five dogs (18-23 kg) were submitted to a 3-hour hypovolemic shock (mean arterial blood pressure, MABP = 50 mm Hg) and received during bleeding 35 mg/kg of MPSS over a 30 min period. Recordings of cardiac output (CO), MABP, regional blood flows in the GDA and superior mesenteric (SMA) arteries were taken every 15 min. The effect of MPSS was appreciated by comparing GDA flow variations in this group with those previously published of a control group comprised of 12 dogs submitted to 3 hours of hypovolemic shock without steroids; operative protocol was in all points similar in both groups. At no time were any significant changes noted when MPSS was added as far as CO and GDA flows were concerned. In other words, the beneficial action of steroids on hypovolemic pancreases cannot be explained by alteration in regional blood flow.

Hypovolemic shock, pancreatic blood flow, and pancreatitis.

Electromagnetic blood flow determinations were carried out on the superior pancreatic duodena (SPDA), the splenic (SA) and the superior mesenteric (SMA) arteries and compared to cardiac output (CO, thermodilution technique) in 12 anesthetized dogs submitted to hypovolemic shock of various duration: 5 dogs underwent a one-hour and 7 a three-hour period of shock. A 50 mm Hg level of mean arterial blood pressure (MABP) was maintained throughout hypovolemia. Dogs were then reinfused. Control preshock values were 4.12 l/min for CO, 38.0 ml/min for SPDA, 405.9 ml/min for SA, and 963.6 ml/min for SMA. SPDA, SA and SMA flows expressed as % of CO amounted to 0.9, 9.8 and 23.4% respectively. No significant changes in SPDA and SMA flows were noted within the first hour of shock. However, from the end of the second hour on, both flows differed significantly (P less than 0.01), SMA increasing from -75.6% of its control value at the end of bleeding to -61.0%, and SPDA decreasing from -75.6 to -86.9%. Similar observations were made when respective flows were considered as % of CO. The SA behaved somewhat in an intermediate fashion. This relative spoliation in pancreatic blood supply as hypovolemia proceeds supports an ischemic etiology of acute pancreatitis (AP), which could account for some of the so-called idiopathic cases of AP.

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow.

The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (141Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25-30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.

The morphological changes of the pancreas in hypovolemic shock and the effect of pretreatment with steroids.

Previous reports from this laboratory have described the effect of hypovolemic shock of varying duration on the exocrine function of the pancreas, and the ability of steroids to reverse the inhibition of secretion observed. This report is a study of pancreatic morphology in prolonged hypovolemia, as well as the effect of steroid pretreatment on the pathology observed. Twelve mongrel dogs were divided into two groups, one with and one without steroid pretreatment. The animals were bled until at least 30-35% of their blood had been withdrawn, or until mean blood pressure (BP) dropped to around 60 mmHg. When BP dropped to 80-90% mmHg, six animals received intravenous (i.v.) prednisolone in 50 cc of 0.9% NaCl, at the rate of 10 cc/min, for a dosage of 30 mg/kg. Of the twelve dogs, six were exposed to 120 min of hypovolemia, and six to 180 min. At the end of the observed hypovolemic period, the blood withdrawn was quickly retransfused. After an hour of recovery, the animals were killed and their pancreases removed. The pancreases were weighed, fixed and examined by light microscopy. Three pancreases were obtained as control from animals not subjected to shock or steroids. The steroid-treated animals displayed an insignificant (5%) increase in pancreatic weight following prolonged hypovolemia. Untreated canine pancreases, on the other hand, showed a significant weight gain (37%, P less than 0.001) after 3 h of hypovolemia. Microscopically, the untreated group revealed marked interstitial edema, hemorrhage and inflammation, as well as focal acinar cell necrosis and fat necrosis, while in the steroid group only very mild edema and inflammatory changes were seen. This study indicates a beneficial effect of steroids on the morphological changes seen in shock-induced pancreatitis in canines and a possible use in the therapy of acute pancreatitis in man.

Physiopathogenic hypothesis of alcoholic pancreatitis: supranormal ecbolic stimulation of the "pancreon" units secondary to the loss of the negative component of pancreas innervation.

In the rat, basal pancreatic secretion is generated and modulated by positive and negative duodeno-pancreatic reflexes. The former activates secretion, the latter acts as a "brake". Impairment of this brake plays a crucial role in the pathogenesis of alcoholic pancreatitis by causing elevation of pancreatic cholinergic tone and inducing increased pancreon ecbolic response to CCK-PZ stimulation. Both factors lead to pancreatic damage by supranormal stimulation of the pancreon.

Effect of partial versus complete pancreatic denervation on pancreatic secretion.

The aim of this study is to compare the effect of various stimuli on pancreatic secretion in two groups of dogs, one undergoing interruption of the cholinergic and adrenergic branches to the pancreas (long arc reflexes), and the second group undergoing total denervation of the pancreas by its isolation from stomach and duodenum (short arc reflexes). Stimulation of pancreatic secretion was accomplished by (a) hormonal, by i.v. secretin and CCK/PZ and (b) reflex stimulation by intraduodenal administration of fat (Na oleate) or amino acids (Aminosyn). After a few weeks of collected data in stimulated controls, the dogs were divided into two groups: (A) Four dogs underwent proximal truncal vagotomy, celiac ganglionectomy, and stripping of the common hepatic and gastroduodenal arteries for 2-3 cm. (B) Four dogs underwent the same procedures, but in addition the pancreas was dissected away from its vascular and nervous attachments to the duodenal wall and pyloric region, as well as from its mesenteric and peritoneal attachments. All animals were then tested with secretin, Cholecystokinin/pancreozymin (CCK/PZ), intraduodenal fat, and intraduodenal amino acids. The data obtained indicate that secretion of pancreatic bicarbonate is dependent on intact local duodeno-pancreatic nervous reflexes. Fat and amino acids stimulate the secretion of bicarbonate only when the attachments of the pancreas to the stomach and duodenum are intact. Stimulation by secretion or CCK, being humoral-hormonal mediators, appears not to be affected by the local denervation.