Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a variety of animal models of acute pancreatitis, cholecystokinin-receptor antagonists have ameliorated the injury response. These results suggest that cholecystokinin may play a primary role in the pathogenesis of pancreatitis initiated by multiple stimuli. In an effort to test this theory, a sensitive and high affinity cholecystokinin-receptor antagonist L364,718 was administered to four different models of acute pancreatitis that were produced in the ex vivo perfused canine pancreas preparation. The four models of pancreatitis were initiated by cerulein infusion, partial duct obstruction with secretin stimulation, oleic acid infusion, and a 2-hour period of ischemia. In each model, pancreatitis was manifest by edema formation, weight gain, and hyperamylasemia during a 4-hour perfusion. In cerulein infusion-induced pancreatitis L364,718 inhibited edema formation and weight gain (31 +/- 5 gm versus 7 +/- 6 gm; p less than 0.05) and significantly decreased plasma amylase activity (36,605 +/- 21,216 U/dl versus 9421 +/- 5149 U/dl; p less than 0.05). The acute pancreatitis induced by the other three stimuli was not ameliorated by L364,718 treatment. We conclude that in the ex vivo-perfused canine pancreas preparation cerulein-induced pancreatitis is mediated at least in part by the cholecystokinin receptor. Early blockade of the cholecystokinin receptor was of no benefit in treating the other models of pancreatitis, suggesting that cholecystokinin is not involved in the early pathogenesis.
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PMID:The role of cholecystokinin in the pathogenesis of acute pancreatitis in the isolated pancreas preparation. 170 26

Previous studies using the isolated ex vivo perfused canine pancreatitis preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p less than 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor.
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PMID:Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis. 200 16

Nineteen combined renal and segmental pancreatic transplantations with enteric exocrine diversion were performed between May 1984 and September 1985. The one year actuarial patient survival rate and pancreatic graft survival rate were 86 and 66 per cent, respectively. Thirteen pancreatic grafts are presently functioning (two to seven months) and all of the recipients are insulin-free. Although graft cold ischemia time was kept low (a mean of 4.6 hours), a moderate graft pancreatitis developed with a peak serum amylase level of 16.8 +/- 2.2 microkatal per liter. Analysis of the fluid drained through an abdominal drain tube placed at the graft site revealed an amylase activity of 280 +/- 110 microkatal per liter on the first postoperative day and rapidly decreasing to a mean of 15 +/- 5 microkatal per liter on day 6. A pancreatic duct catheter was used to divert the exocrine juice to the exterior during the first few postoperative weeks thereby promoting healing of the pancreaticoenteric anastomosis. The volume of pancreatic juice from the ductal catheter was quite low in the first postoperative days but then rose to reach a plateau level of 500 to 600 milliliters. The amylase activity and the lipase concentration in the pancreatic juice was very high (9,100 +/- 2,450 microkatal per liter and 11.1 +/- 4.4 grams per liter, respectively) during the first postoperative day but then gradually decreased to reach a steady level after four to seven days. Intravenous administration of secretin induced a sixfold increase in the flow of pancreatic juice. An intravenous infusion of somatostatin significantly reduced the flow of pancreatic juice and the amylase activity and lipase concentration in the juice but did not abolish the secretin induced increase in pancreatic secretion.
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PMID:Studies on the exocrine secretion of segmental pancreatic grafts in humans. 243 63

In a previous report from this laboratory, 1 h of hypovolemia induced a significant decrease in pancreatic flow, bicarbonate and enzyme secretion. These parameters recover after restoration of blood volume, but never return to pre-shock levels. Furthermore, increasing the period of hypovolemia produced further decreases in pancreatic flow and bicarbonate secretion only. Enzyme secretion, however, rose significantly, probably due to leakage of protein through damaged cell membranes. Prolonged hypovolemia was also accompanied by visible edema. This model of secretory changes induced by fixed periods of hypovolemic shock is ideal to study the effect of steroids on secretion and to assess its possible cytoprotective properties against early induced ischemia pancreatic pathology. Pancreatic secretion was collected by cannulation of the main pancreatic duct in 12 anesthetized dogs. Secretin was administered by continuous intravenous (i.v.) infusion at 4 U/kg/h. Four 15-min samples of pancreatic juice were collected. Then the dogs were bled, withdrawing 25-30% of total blood volume or until the mean blood pressure dropped to about 60 mmHg. At this point, 30 mg/kg of methyl prednisolone were given in 50 cm3 of NaCl i.v. to six animals. Blood samples for amylase and 15-min collections of pancreatic juice for volume, bicarbonate and enzymes were obtained during hypovolemia, as well as during and following the restoration of blood volume. The responses of the two groups differed as follows: (1) Instead of the increase in protein enzyme secretion seen in the non-steroid group with increased duration of hypovolemia, steroid-treated dogs displayed a significant decrease in protein output.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of steroid administration on pancreatic secretion during and after hypovolemic shock. 244 71

The present study was designed to establish an in vitro perfused porcine pancreas preparation as a model for testing the effect of organ protective solutions on stimulated pancreatic endocrine and exocrine secretion. The pancreas was prepared and perfused for 10 min with Euro Collins solution, thereafter it was stored in the cold (4 degrees C) for various times. After 3-h and 6-h ischemia pancreatic insulin release in response to glucose was not significantly affected. After 12-h ischemia reduced pancreatic insulin secretin, increased perfusion pressure, and increased amylase and lipase release indicated pancreatic damage. Complete pancreatic dysfunction was seen after 24-h and 48-h ischemia with massive increase in perfusion pressure and low insulin secretion which did not follow a glucose-dependent release pattern, while amylase and lipase concentrations in the perfusion medium increased. Stimulated exocrine pancreatic secretion was significantly decreased already after 3-h ischemia and completely lost after 12 h.
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PMID:The perfused porcine pancreas as a model for testing organ protective solutions. 247 64

Recent experimental work has suggested that oxygen-derived free radicals may play an important role in initiating the early capillary injury in acute pancreatitis. Data from models of ischemic injury in other organs have suggested the enzyme xanthine oxidase is important in generating oxygen-derived free radicals. The present study was performed to determine whether xanthine oxidase is the source of free radical production in experimental pancreatitis. Utilizing the isolated, perfused, ex vivo canine pancreas preparation, three models of pancreatitis were initiated with (1) free fatty acid infusion (FFA), (2) partial duct obstruction and secretin stimulation (POSS), and (3) ischemia (ISCH). In each model, during a 4-hour perfusion, edema developed, weight gain occurred (FFA 120.6 +/- 21.1 gm; POSS 44.5 +/- 6.9 gm; ISCH 63.3 +/- 14.0 gm), and the serum amylase became elevated (FFA 1827 +/- 397 u/dl; POSS 10,171 +/- 1487 u/dl; ISCH 1860 +/- 365 u/dl). When the xanthine oxidase enzyme inhibitor allopurinol was added to the perfusate prior to the 4-hour perfusion, edema formation was absent or minimal, weight gain was significantly less (FFA 15.2 +/- 2.5 gm p less than 0.05; POSS 8.8 +/- 2.7 gm p less than 0.001; ISCH 12.3 +/- 2.8 gm p less than 0.01), and the amylase remained normal or the elevation was significantly decreased (FFA 996 +/- 189 u/dl p less than 0.05; POSS 3021 +/- 1074 u/dl p less than 0.001; ISCH 993 +/- 214 u/dl p less than 0.002). These data confirm that oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis, and suggest that the enzyme xanthine oxidase may well be the source of their production.
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PMID:The pathogenesis of acute pancreatitis. The source and role of oxygen-derived free radicals in three different experimental models. 258 19

In studies on the pathogenesis of ischemic cell injury and of other pancreatic diseases the knowledge of the actual pancreatic energy state is an important factor. Therefore, it would be advantageous to have a simple and inexpensive method to determine this parameter and its alterations in the pancreas. At uniform hormonal stimulation, the extent of exocrine pancreatic secretion showed a clear dependence on energy supply in this organ. The degree of pancreatic juice edema formed after bolus injection of cholecystokinin and secretin at ductal occlusion was found to be the most sensitive and reproducible measure of the functional capacity of the pancreatic energy metabolism. While this parameter can be applied to experimental studies, only, the juice volume secreted could be determined under clinical conditions, too. Both parameters of pancreatic secretion were clearly decreased after preceding short-term ischemia and recovered after an adequate interval of reperfusion.
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PMID:Pancreatic exocrine secretion--a measure of the functional capacity of the pancreatic energy metabolism. 258 44

A new experimental model of chronic pancreatitis was produced by a combination of chronic ischemia and incomplete obstruction of the pancreatic duct. Ischemia was induced by ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery. Incomplete ductal obstruction was achieved by ligation and separation of the minor pancreatic duct and placement of a polyethylene tube in the major pancreatic duct. Macroscopic examination at 6 months after model preparation showed that the pancreas was hard, with severe inflammatory change. In the secretin test, the flow rate of pancreatic juice, amylase output and bicarbonate concentration were significantly reduced as compared with the controls. Pancreatography revealed dilatation and meandering of the major pancreatic duct and poor visualization of its secondary and tertiary bifurcations. The histopathological findings consisted of a decrease in the pancreatic parenchyma, replacement of fat, severe inflammatory cell infiltration, extensive fibrosis and tubular complexes. This model most closely resembles human chronic pancreatitis, and is a very useful instrument.
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PMID:New canine model of chronic pancreatitis due to chronic ischemia with incomplete pancreatic duct obstruction. 322 67

Acute pancreatitis may be initiated in the ex vivo, perfused canine pancreas preparation by a variety of stimuli. These include oleic acid infusion (FFA), partial duct obstruction with secretin stimulation (POSS), and a 2-hour period of ischemia (ISCH). In each model, pancreatitis is characterized by weight gain, edema, and hyperamylasemia. Oxygen-derived free radicals such as superoxide, hydrogen peroxide, and the hydroxyl radical are highly reactive toxic substances that are normally produced in small amounts during oxidative metabolism. Ordinarily, these substances are detoxified by endogenous intracellular enzymes called free radical scavengers (FRS), such as superoxide dismutase (SOD) and catalase (CAT). These studies were undertaken to evaluate the possible role of oxygen-derived free radicals in the initiation of acute pancreatitis in the isolated canine model. All preparations were perfused for 4 hours with autologous blood. Controls (N = 6): these glands remained normal in appearance, gained minimal weight (6 +/- 1 g), and serum amylase remained normal (less than 1000 u/dl). FFA pancreatitis, FFA alone (N = 6): these glands became edematous, gained weight (113.5 +/- 27.0 g), and developed hyperamylasemia (2087 +/- 387 u/dl). FFA + FRS (N = 6), SOD (50 mg) and CAT (50 mg) were added to the perfusate at time zero: these glands became only minimally edematous, gained less weight (31.8 +/- 10.1 g, p less than 0.05), and amylase remained normal (p less than 0.05). POSS pancreatitis, POSS alone (N = 8): these glands became edematous, gained weight (38.6 +/- 4.6 g), and developed marked hyperamylasemia (9522 +/- 3226 u/dl). POSS + FRS (N = 6): these glands did not develop edema, gained less weight (15.1 +/- 2.6 g, p less than 0.05), and serum amylase only increased to 1815 +/- 343 u/dl, (p less than 0.05). ISCH pancreatitis, ISCH alone (N = 6): these glands became edematous, gained weight (75.8 +/- 25 g), and developed hyperamylasemia (1679 +/- 439 u/dl). ISCH + FRS (N = 6): these glands did not develop edema, gained only 18.3 +/- 9.0 g (p less than 0.005), and serum amylase remained normal (p less than 0.05). These studies demonstrate that, in this canine preparation, acute pancreatitis is significantly ameliorated by oxygen-free radical scavengers. Since this was true whether the pancreatitis was produced by FFA infusion, POSS, or ischemia, it suggests that oxygen-derived free radicals may mediate a common essential step in the pathogenesis of all forms of pancreatitis.
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PMID:The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. 620 83

The influence of a short-term ischemia of the pancreas for the pathogenesis of a hemorrhagic necrotising pancreatitis was investigated in 28 mongrel dogs. Ischemia of the pancreas in 20 minute intervals repeated three times did not leave any macroscopic, histologic or electron microscopic changes and no alterations of the level of the alpha-amylase, the lipase, and the glucose in the serum. An ischemia of 20 minutes' duration by starvation of the celiac artery and the superior mesenteric artery produces a hemorrhagic necrotising pancreatitis under the precondition of a following pancreatic edema by ligature of the pancreatic duct and secretomotoring with secretin and pancreozymin. The necrosis starts histologically in the perilobular adipose and affects the parenchyma later. Whether the lipase is the starting enzyme for the acute pancreatitis or only conditions the early adipose necrosis should be discussed after these findings. Already a fugitive pancreatic edema produces a hemorrhagic necrotising pancreatitis after previous ischemic damage.
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PMID:[Animal experiment studies on the role of ischemia in the pathogenesis of acute pancreatitis]. 633 88


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