Pancreatic tissue and ductal pressures in chronic pancreatitis.
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Animals↗
Biomedical subjects
H A Reber
Publications and source records attributed to H A Reber.
Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas.
In the pancreas, calcitonin gene-related peptide (CGRP) immunoreactivity has been described in nerve fibers and in distinct types of islet cells. This unique, apparently species-specific cell-type expression prompted the present investigation to clarify further the pattern of CGRP immunoreactivity in different mammalian species (i.e., different strains of rats, mice, guinea pigs, rabbits, cats, dogs, pigs, and humans) commonly used for functional and anatomical studies of the pancreas by means of immunohistochemistry using three different CGRP antibodies. In each species, CGRP-immunoreactive neurites innervate the exocrine and endocrine compartments, the vasculature, and the intrapancreatic ganglia, where they form dense networks encircling unstained cell bodies. The only exception is the pig pancreas, where the islets appear to be devoid of immunoreactive fibers. The overall density of immunoreactive pancreatic axons in different species is as follows: rat, mouse, and rabbit greater than guinea pig greater than or equal to pig and cat much greater than dog and human. CGRP-immunoreactive endocrine cells appear to be restricted to the rat pancreas, where they form a subpopulation of somatostatin-containing D cells. In contrast, in mouse, guinea pig, cat, dog, and human pancreas, a homogeneous staining of the core of the islets, where insulin-producing B cells are located, was visualized in sections incubated with the rabbit CGRP antiserum at 4 degrees C, but not at 37 degrees C (an incubation temperature that does not affect the islet cell staining in the rat nor the fiber labeling in any species). Furthermore, the staining of islet B cells was not reproducible with all the CGRP antibodies used, all of which comparably stain nerve fibers in each species, and islet D cells in the rat. Immunoreactive islet cells were not visualized in pig and rabbit pancreas. These results are consistent with the hypothesis that the expression of CGRP in nerve fibers is a common feature of mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to the D cells of the rat pancreas.
Animals↗
Pancreatic ductal and interstitial pressures in cats with chronic pancreatitis.
We investigated the etiology of interstitial hypertension in chronic pancreatitis by examining the relationship between pancreatic ductal and interstitial pressures in cats. The main pancreatic duct was cannulated in the tail of the gland and perfused at 1, 2, or 5 ml/hr, to simulate pancreatic secretion. Intraductal and interstitial pressures were measured in four groups of animals: (1) normal cats; (2) normal cats after acutely narrowing the main duct to 25% of its original diameter; (3) normal cats after encasing the body and tail in a rigid latex capsule; and (4) cats with chronic pancreatitis created by narrowing the main duct five weeks earlier. Duct perfusion increased intraductal pressure in all of the cats, but significantly more in groups 2, 3, and 4 compared to group 1. Pancreatic interstitial pressure was unchanged by duct perfusion in groups 1 and 2, but increased in groups 3 and 4. We concluded that the compliant tissue of the normal pancreas expanded to effectively dissipate the increase in duct pressure associated with duct perfusion. In chronic pancreatitis, the inelastic parenchyma and capsule limited the distensibility of the gland, which resulted in elevated interstitial pressures during duct perfusion.
Animals↗
Influence of levamisole on pancreatic infection in acute pancreatitis.
We investigated the effect of levamisole on pancreatic infection in a model of acute pancreatitis (AP) in cats. Animals with and without AP received Escherichia coli intravenously. Blood was then taken at intervals for culture. AP reduced phagocytic function by 28% as measured by the rate of bacterial disappearance from the blood (p less than 0.03). In other cats, AP was induced, and E. coli were placed into the pancreatic duct. Levamisole was given orally in some cats; the remainder were untreated. Control cats (neither AP nor levamisole) also received E. coli. Seven days later, pancreases from all control cats were sterile. In AP cats, the pancreatic infection rate was 73%. Levamisole reduced the rate of infection to 22% (p less than 0.03). We concluded that phagocytic function was impaired in cats with AP. Levamisole reduced the rate of pancreatic infection.
Animals↗
Patterns of innervation of vasoactive intestinal polypeptide, neuropeptide Y, and gastrin-releasing peptide immunoreactive nerves in the feline pancreas.
In this study, we performed a detailed analysis of the immunoreactive (IR) patterns and tissue distribution of vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) in the feline pancreas by means of immunohistochemical and radioimmunological techniques. Immunoreactivity for each peptide is localized to varicose nerve fibers distributed throughout the exocrine and endocrine pancreas, with some differences in the density and pattern of fiber distribution. In the acinar and stromal compartments, VIP-IR processes have a higher density than NPY- and GRP-containing fibers, the latter being the least abundant. The vasculature receives a particularly prominent NPY innervation, while GRP- and VIP-IR fibers are found occasionally in association with blood vessels. Around ducts, NPY- and VIP-IR nerves are more numerous than those positive for GRP-IR, which are quite sparse. One of the most interesting findings of the present work is the visualization of all peptide-IRs both in neuronal cell bodies and fibers within the intrapancreatic ganglia. VIP-IR is observed in virtually all ganglion cells, while GRP- and NPY-IRs are seen in a few neuronal cells. VIP and NPY tissue levels are much higher than GRP concentrations in all regions of the pancreas. VIP content in the head and body is greater than in the tail. The morphological relationship of VIP-, NPY-, and GRP-IR fibers with different pancreatic structures is consistent with specific peptidergic neural inputs in the regulation of pancreatic functions.
Animals↗
The low-pressure duct perfusion model of acute pancreatitis.
The low-pressure duct perfusion model reliably produces acute pancreatitis in cats. The main pancreatic duct is made permeable in one of several ways: the perfusion of glycodeoxycholic acid along the main pancreatic duct, the administration of intragastric ethanol, the stimulation of pancreatic secretion into an obstructed duct, or the creation of acute hypercalcemia. Active pancreatic enzymes are then perfused through the main pancreatic duct via a catheter inserted into the duct in the tail of the gland, and acute edematous pancreatitis results. Simultaneous infusion of 16,16-dimethylprostaglandin E2 converts acute edematous into acute hemorrhagic pancreatitis. Histologically, the characteristic changes of human acute pancreatitis are manifest 24 h later: necrosis, polymorphonuclear leukocyte infiltrate, hemorrhage and edema.
Acute Disease↗
Pancreatic blood flow in cats with chronic pancreatitis.
Pancreatic blood flow and its relationship to pancreatic interstitial pressure were investigated in a model of chronic pancreatitis in cats using a hydrogen gas-clearance technique with an intraductal electrode. The intraductal technique correlated well with blood flow measurements made using gamma-labeled microspheres (r = 0.88, P less than 0.001). In control cats, the basal blood flow of 69.1 +/- 9.5 mL.min-1.100 g-1 increased by 25% to 86.2 +/- 11 mL.min-1.100 g-1 with secretory stimulation (P less than 0.05). Interstitial pressure was -0.02 +/- 0.3 mm Hg and did not change significantly with stimulation. In cats with chronic pancreatitis, basal interstitial pressure was 1.8 +/- 0.5 mm Hg and basal blood flow 39.9 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Stimulation of the chronic pancreatitis gland increased the pressure to 3.0 +/- 0.4 mm Hg (P less than 0.01) and reduced flow 15% to 34.2 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Papaverine increased blood flow in control and chronic pancreatitis cats without altering tissue pressure, suggesting that despite the reduced basal blood flow, the ability to increase blood flow was preserved in chronic pancreatitis. The increased interstitial pressure associated with secretion appeared to limit the gland's normal hyperemic response in this model of chronic pancreatitis.
Animals↗
The influence of ethanol on pancreatic blood flow in cats with chronic pancreatitis.
BACKGROUND: The mechanism by which ethanol predisposes to acute pancreatitis, especially in established chronic pancreatitis, is not known. Here we studied the effects of acute ethanol ingestion on pancreatic blood flow in chronic pancreatitis, a setting characterized by diminished basal blood flow to the pancreas. METHODS: Obstructive pancreatitis was created by partial duct ligation for 3 weeks in nine cats. Controls (n = 8) were not operated on. Blood flow was measured in anesthetized animals with a hydrogen gas clearance technique and an intraductal electrode. Pancreatic interstitial pressure, systemic and portal blood pressures, and serum ethanol levels were recorded, and pancreatic vascular resistance was calculated. Measurements were made before and for 2 hours after 20 cc of 40% (wt/vol) ethanol was instilled into the stomach. RESULTS: Basal flow was reduced in the obstructed pancreas to 51% of normal. Both groups showed an acute decrease in blood flow when ethanol was given. A more steep (50% of baseline) and a more prolonged (120 minutes) fall was observed in the pancreatitis group than in controls (31% and 60 minutes, respectively). The decline in blood flow correlated with increases in interstitial pressure and vascular resistance. CONCLUSIONS: Acute ethanol ingestion sharply reduces pancreatic blood flow, especially in glands with chronic pancreatitis.
Animals↗
Acute pancreatitis--another piece of the puzzle?
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Acute Disease↗
A study of the time course of conversion of edematous to hemorrhagic pancreatitis.
We studied the conversion of acute edematous pancreatitis (AEP) to acute hemorrhagic pancreatitis (AHP) in an experimental model in cats. In the model, 16,16 dimethyl PgE2 effects this conversion by increasing microvascular permeability. First, we induced AEP in cats and then gave PgE2 at increasing intervals after the induction of AEP to see how long an interval would still allow conversion. In 6 groups of cats, PgE2 was administered for 2 h, starting at 2, 4, 6, 8, 10, or 12 h after the creation of AEP. Twelve h later, the cats were sacrificed and the pancreases were graded for inflammation and hemorrhage. Significant pancreatic hemorrhage did not occur when the PgE2 was administered at 12 h compared to 2 h. Next, we determined that PgE2 still retained its ability to increase pancreatic vascular permeability when administered 12 h after the creation of AEP. This was done by perfusing a marker molecule through the MPD (fluorescein isothiocyanate labeled dextran: FITC-D, mol wt 20,000) and then finding it in portal venous blood (PVB). The presence of FITC-D in PVB signified increased vascular permeability, since normally none was present. We concluded that conversion of AEP to AHP was possible during the first 12 h after induction of AEP. Lack of conversion at 12 h was not caused by a lack of vascular reactivity at that time.
16,16-Dimethylprostaglandin E2↗
Surgical treatment of pancreatic cancer. The United States experience.
About 28,000 new cases of pancreatic cancer are diagnosed yearly in the United States. The diagnosis is now made up to two months more quickly than just a few years ago, but this has had no impact on survival. In most institutions, 20-25% of patients have resectable lesions. The standard operation is still the Whipple pancreaticoduodenectomy, but many surgeons now use the pylorus preserving modification of that procedure. The operative mortality rate has fallen to less than 5%. The five-year survival rate after a resection for attempted cure is about 9%. Palliation requires cholecysto(docho)jejunostomy and gastrojejunostomy, which is often done prophylactically. The operative mortality rate in patients undergoing palliation is less than 10% (recent UCLA experience), and the average survival is seven months.
Adenocarcinoma↗
The antiinflammatory effect of dopamine in alcoholic hemorrhagic pancreatitis in cats. Studies on the receptors and mechanisms of action.
Hemorrhagic pancreatitis was induced in cats by perfusing pancreatic enzymes through a pancreatic duct after the administration of intragastric ethanol. Dimethyl prostaglandin E2 was administered concurrently. In the first study, dopamine's antiinflammatory effect on the pancreas was determined in the presence of haloperidol, propranolol, or both. Next, dopamine's effects on blood flow in the normal and inflamed pancreas were compared using a hydrogen gas-clearance technique. In the final study, the effect of dopamine on fluorescein isothiocyanate-labeled dextran leakage from the pancreatic duct to portal venous blood was investigated. It was found that blockade of either dopamine or beta-adrenergic receptors reduced, and blockade of both receptors completely eliminated, the antiinflammatory effect. Dopamine had no effect on pancreatic blood flow in normal cats. In pancreatitis, although dopamine transiently reduced blood flow, after an hour flow had returned to normal. Dopamine reversed the leakage of fluorescein isothiocyanate-labeled dextran from the pancreatic duct caused by ethanol and by ethanol and prostaglandin E2. It was concluded that dopamine ameliorated pancreatitis by reducing pancreatic ductal and/or microvascular permeability rather than by altering pancreatic blood flow. The antiinflammatory effect was mediated by both dopamine and beta-adrenergic receptors.
Acute Disease↗
Experimental evidence of beneficial effects of ductal decompression in chronic pancreatitis.
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Animals↗
Surgical intervention in acute pancreatitis: when and how.
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Acute Disease↗
New perspectives in the surgical management of chronic pancreatitis.
Although the etiology of pain in chronic pancreatitis remains uncertain, that symptom remains the most common indication for surgery in these patients. Current endoscopic and imaging techniques now permit accurate definition of the morphology of the disease. Thus, surgical intervention can be more selectively applied to address specific abnormalities. Pancreaticojejunostomy should be the first line of surgical therapy if the ductal system is dilated. When, in addition, the head of the pancreas is enlarged and inflamed, the operation should include a localized resection of the head, preserving the stomach and duodenum. If the duct is not dilated, some form of pancreatic resection is indicated. The resection should be limited to the most severely diseased part of the pancreas. Efforts should be made to preserve as much pancreatic tissue as possible, while maintaining normal gastrointestinal continuity. In this way, the nutritional and metabolic consequences of pancreatic resection will be minimized.
Chronic Disease↗
The effect of dopamine in a model of biliary acute hemorrhagic pancreatitis.
Perfusion of the main pancreatic duct in cats with a dilute solution of bile salts increases ductal permeability. Subsequent perfusion of a permeable duct with activated pancreatic enzymes results in acute edematous pancreatitis. Simultaneous infusion of 16-16 dimethyl-PgE2 converts edematous pancreatitis to acute hemorrhagic pancreatitis (AHP). AHP may be associated with a reduction in pancreatic blood flow; it is certainly associated with increases in microvascular permeability. Low dose dopamine is a splanchnic vasodilator and may also reduce pancreatic microvascular permeability through beta agonist effects. In these studies, we investigated the effect of dopamine in an established feline model of biliary AHP. We also studied its effect on blood flow in both normal pancreas and after induction of AHP. We found that dopamine significantly reduced the degree of pancreatic inflammation, even when administered up to 12 h after onset of biliary AHP. However, the drug had no significant effect on blood flow either in normal pancreas or in the gland affected by hemorrhagic pancreatitis. We concluded that the effect of dopamine was most likely due to its ability to reduce pancreatic microvascular permeability.
16,16-Dimethylprostaglandin E2↗
Low dose dopamine protects against hemorrhagic pancreatitis in cats.
Acute hemorrhagic pancreatitis (HP) is probably associated with decreased blood flow in its early phases, as well as with an increase in microvascular permeability. Dopamine (DOP; 5 micrograms/kg-min) is a splanchnic vasodilator, and also has beta-adrenergic effects that can prevent increases in microvascular permeability. We hypothesized that low dose dopamine might have beneficial effects on both blood flow and microvascular permeability, thus ameliorating the severity of the disease. We studied its actions in an animal model of HP. In anesthetized cats, intragastric ethanol (20 ml/40% solution) rendered the main pancreatic duct permeable to pancreatic enzymes. Then the duct was perfused from tail to head with 0.5 ml of activated pancreatic enzymes for 1 hr. To create HP, 16,16-dimethyl prostaglandin E2 (2 micrograms/kg-hr, iv) was given for 2 hr to increase blood flow and microvascular permeability. Seven of eight cats developed HP in 24 hr. Control cats received no additional drugs. Two experimental groups received DOP (6 hr infusion) begun either (1) at the onset of enzyme perfusion or (2) 12 hr later. Each pancreas was examined after 24 hr and graded (1-4) histologically for edema, hemorrhage, polymorphonuclear cell infiltrate, and architectural loss. An inflammatory score (IS) from 0 to 16 was thus created (higher scores = greater damage). The results showed an IS of 10.9 +/- 1.8 for the controls, 3.3 +/- 0.5 for the immediate treatment group, and 7.2 +/- 1.8 for the delayed treatment group. Both treated groups had a significantly better IS (t tests, P less than 0.001 and P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Surgical palliation for pancreatic cancer. The UCLA experience.
We reviewed the records of 340 patients with a tissue diagnosis of pancreatic cancer treated at UCLA Medical Center between 1973 and 1988. Sixty-one patients underwent pancreatic resection (group I), 173 had some form of surgical palliation (group II), and 106 had neither (group III). The diagnosis was made 1 to 2 months more quickly in the last 8 years of the review than in the first 8 years, but the effect of early diagnosis on curability was negligible. Biliary obstruction was best treated by cholecystojejunostomy or choledochojejunostomy, which were equally effective. Anastomoses to the jejunum were safer and more effective than were those to the duodenum for the relief of biliary obstruction. Gastrojejunostomy should be performed prophylactically as well as therapeutically. It was effective and safe in both settings. Surgical palliation for pancreatic cancer was generally effective and was associated with an operative mortality rate of less than 10%. However morbidity was high, with significant complications occurring in one third of cases.
Adolescent↗