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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis has been investigated in a series of studies using an ex vivo, perfused canine pancreas preparation. Three models of experimental acute pancreatitis have been developed in this preparation: ischemic pancreatitis, gallstone pancreatitis, and alcohol-induced pancreatitis. In each model, the pancreas becomes edematous, gains weight, and the perfusate develops hyperamylasemia during the 4 hour period of perfusion. Pretreatment with the free radical scavengers superoxide dismutase and catalase significantly ameliorates these manifestations of pancreatic injury in each of the three models. The source of the free radical generation was investigated by pretreating the preparation with allopurinol, a quite specific inhibitor of xanthine oxidase. In each of the three models, this also significantly ameliorated the injury process. These experiments demonstrate that oxygen-derived free radicals, generated by activated xanthine oxidase, appear to play a central role in the pathogenesis of acute pancreatitis in these models. These findings shed light on the fundamental pathophysiology of this disease and may provide the basis for more effective therapy in the future.
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PMID:Oxygen-derived free radicals and acute pancreatitis: a review. 352 21

Restoration and maintenance of intravascular volume is crucial in acute pancreatitis to prevent hypotension and ensure normal organ perfusion. This study evaluated the hemodynamic and metabolic effects of adequate versus inadequate fluid replacement on the pancreas in a canine model of acute experimental pancreatitis. Bile-trypsin pancreatitis (BTP) was induced in 14 conditioned mongrel dogs. Lactated Ringer's solution was administered intravenously at high (HIR) and low (LIR) infusion rates (6.5 and 1.75 ml/kg/hr, respectively) to 7 dogs each for 4 h. Seven sham-operated controls (CON) received lactated Ringer's at 6.5 ml/kg/hr for 3 hr. Mean arterial pressure remained unchanged in all groups. Central venous pressure decreased in the LIR group (P less than 0.05) and remained unchanged in the other groups. Cardiac index fell uniformly (P less than 0.05) in all groups. Pancreatic blood flow (Qp) decreased in the LIR group (73%) to a significantly greater extent than in the HIR (23%) and CON (8%) groups, and in the HIR group significantly more than in the CON group. The fall in pancreatic oxygen consumption (O2Cp) in both the pancreatitis groups was significant compared to the rise in the CON group. Final changes in Qp and O2Cp from baseline were significant only in the LIR group. We conclude that inadequate crystalloid replacement after BTP results in a progressive fall in Qp and O2Cp. Vigorous fluid replacement incompletely prevents these effects.
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PMID:Pancreatic response to crystalloid resuscitation in experimental pancreatitis. 368 3

Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis in the ex vivo perfused canine pancreas model. In other organ systems, circulating leukocytes may serve as one source of oxygen-derived free radical production. The current experiments were designed to evaluate the role of circulating leukocytes in the generation of injury in this model. Four experimental groups of animals were studied: group I consisted of controls (n = 6); group II had white blood cell (WBC) depletion (n = 4) in which the recirculating whole blood perfusate was depleted of 98% of its circulating leukocytes; group III had oleic acid infusion (FFA) alone (n = 9), which induced pancreatitis; group IV had WBC depletion and FFA (n = 6), in which oleic acid was infused after depletion of the circulating leukocytes in the perfusate. During the 4-hour perfusion period, the pancreatic preparations were monitored hourly for the development of edema, weight gain, and release of alpha-amylase into the perfusate. Animals in groups I and group II manifested no gross edema, gained minimal weight, and did not manifest hyperamylasemia. Leukocyte depletion alone had no effect. In group IV animals marked edema, significant weight gain, and hyperamylasemia developed to the same extent as in group III animals. These results demonstrate that circulating leukocytes are not essential to the development of pancreatitis in this model and suggest that another source of oxygen-derived free radicals mediates this injury.
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PMID:The role of leukocytes in the production of oxygen-derived free radicals in acute experimental pancreatitis. 382 56

Oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis in the isolated perfused canine pancreas. We have previously found that pretreatment with allopurinol inhibits xanthine oxidase--apparently the primary source of free radical generation in this model--and prevents the initial development of pancreatitis. In these experiments, we evaluated whether allopurinol administered after the onset of pancreatitis would arrest the progression of the disease process. Edema formation, weight gain, and the release of amylase activity into the perfusate in the ex vivo perfused canine pancreas model were monitored during a 4-hour perfusion period. There were six experimental groups: Group I (control) received no treatment, group II (allopurinol alone) received only allopurinol (100 mg) at the start of perfusion, and groups III through VI were each given an infusion of 0.3 ml of oleic acid (FFA) over a 1-hour period to initiate acute pancreatitis. Group III (FFA alone) received no other treatment. In group IV (pretreatment with allopurinol), group V (concurrent treatment with allopurinol), and group VI (posttreatment with allopurinol), allopurinol (100 mg) was administered 1 hour before, concurrent with, or at the end of the FFA infusion, respectively. Pretreatment with allopurinol prevented edema formation, markedly attenuated weight gain, and the release of amylase caused by the FFA infusion. Administration of allopurinol concurrent with the FFA infusion provided only partial protection, whereas posttreatment with allopurinol failed to arrest the progression of the injury process. Therefore, the use of allopurinol to inhibit oxygen-derived free radical production from xanthine oxidase prevented the development of acute pancreatitis in this model; however, treatment with allopurinol after initiation of the disease process failed to arrest the progression of acute pancreatitis.
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PMID:Temporal efficacy of allopurinol during the induction of pancreatitis in the ex vivo perfused canine pancreas. 382 61

In 16 patients with necrotizing pancreatitis and in 6 patients with edematous-interstitial pancreatitis, hemodynamic studies were conducted between the first and the 12th day after the onset of illness. Patients with necrotizing pancreatitis had a high cardiac index of 4.47 +/- 0.75 L/min X m2 and a low total peripheral vascular resistance of 884 +/- 180 dyn X s/cm5, a low mean pulmonary vascular resistance of 84.3 +/- 25.7 dyn X s/cm5, and a high pulmonary shunt fraction of 24.2% +/- 6.6% of the cardiac output. This hyperdynamic vascular pattern was not found in patients with edematous-interstitial pancreatitis associated with gallstone disease. The group of patients with edematous-interstitial pancreatitis had a cardiac index of 3.21 +/- 0.8 L/min X m2, a total peripheral vascular resistance of 1337.8 +/- 248.2 dyn X s/cm5, a mean pulmonary vascular resistance of 130.7 +/- 48.2 dyn X s/cm5, and a pulmonary shunt fraction of 13.6% +/- 3.5% of the cardiac output. There was a significant difference between the patients with necrotizing pancreatitis and those with edematous-interstitial pancreatitis in the following hemodynamic parameters: heart rate (p less than 0.02), cardiac index (p less than 0.01), total peripheral vascular resistance (p less than 0.001), arteriovenous oxygen difference (p less than 0.02), and pulmonary shunt fraction (p less than 0.01). These findings in patients with necrotizing pancreatitis demonstrate an opening of intrapulmonary shunts and peripheral vasodilatation probably due to the release of pancreatitis-associated toxic agents in the early phase of the disease.
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PMID:Hemodynamic data pattern in patients with acute pancreatitis. 394 Feb 59

Microcirculatory derangements in the pancreas associated with acute pancreatitis may contribute to a low-flow state and lead to pancreatic necrosis. This study investigated the effects of glucagon, a selective mesenteric arterial dilator, on pancreatic ischemia in canine bile-trypsin-induced pancreatitis (BTP). Measurements of cardiac Index (CI), total pancreatic blood flow (QP), pancreatic oxygen consumption (O2CP), and pancreatic arteriovenous shunt flow (QAVS) were obtained prior to and after inducing BTP. Bile-trypsin-induced pancreatitis was induced in 18 dogs. Nine received lactated Ringer's solution alone (LRPAN) at 6.5 mL/kg/hr, nine received lactated Ringer's solution plus continuous Intravenous (IV) glucagon hydrochloride (GLUPAN) at 1.0 micrograms/kg/min, and nine undergoing periportal dissection without BTP received IV glucagon (GLUCON). Following BTP, CI, QP, and O2CP decreased significantly and QAVS remained unchanged in crystalloid-treated animals (LRPAN). Glucagon administration (GLUPAN) transiently increased CI and QP but failed to improve O2CP and did not change QAVS. The decrease in O2CP observed after BTP in association with a constant QAVS suggests a metabolic block to oxygen uptake at the cellular level. Glucagon in pharmacologic doses does not reverse abnormalities in O2CP and is therefore of questionable physiologic benefit in the treatment of acute pancreatitis.
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PMID:Efficacy of pharmacologic glucagon in acute experimental pancreatitis. 397 Jun 71

For medical treatment of acute pancreatitis, only very few effective measures can be recommended. To put the gland to rest, the patient has to be maintained in a fasting state. Additionally, Cimetidine should be administered intravenously. A properly functioning nasogastric tube is an efficacious method of inducing the pancreas to rest. To maintain an adequate blood volume and in protecting the microcirculation of pancreas, the use of intravenous fluids that include colloids, is important. Sufficient replacement of electrolytes evidently seems to be indicated. Drug therapy consists of the administration of analgetics and of an adjuvant use of calcitonine or somatostatine, for reducing the pancreatic flow. Aprotinine given early and in sufficient amounts is to be recommended. Antibiotic prophylaxis should be utilized only when pancreatitis associated with biliary tract disease or postoperative pancreatitis seems to be apparent. Whenever systemic hypotension and shock occurs, plasma or dextran, together with sufficient but controlled amounts of intravenous fluids, must be administered. In acute renal failure dopamine has been used with success. Peritoneal dialysis or hemodialysis as an ultimate measure, has to be considered. In the case of respiratory distress syndrome, oxygen by nasal catheter must be applied.
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PMID:[Medical treatment of acute pancreatitis (author's transl)]. 615 71

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

Twenty-three patients with acute fulminant pancreatitis were studied. The diagnosis was confirmed at laparotomy in every case. Blood samples for the assay of phospholipase A2 were collected for 14 days, and the pulmonary status of the patients was followed by monitoring the blood gases and the inspired oxygen fraction and studying a derived variable, the alveolar to arterial oxygen tension difference--the arterial oxygen tension ratio (A--aDo2/PaO2). The serum phospholipase A2 activities correlated with the changes in pulmonary function and with the outcome of the disease. Eight patients succumbed and they showed higher phospholipase A2 activities and A--aDo2/PaO2 ratios than the five patients who survived after major complications and the ten patients who survived without major complications. The results suggest that in acute fulminant pancreatitis serum phospholipase A2 activity correlates with the severity of the pulmonary changes. Furthermore, it seems to reflect the prognosis.
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PMID:Serum phospholipase A2 and pulmonary changes in acute fulminant pancreatitis. 629 71

Evidence is presented that supports a role of oxygen free radicals in the pathogenesis of various disorders of the digestive system. In the intestine, there is evidence that oxygen radicals play an important role in the endothelial and epithelial damage associated with certain models of ischemia. The mechanism for superoxide production in this condition differs from that described for other pathologic states (i.e., oxygen toxicity and neutrophil-mediated inflammation). This mechanism involves the reaction of xanthine oxidase, hypoxanthine, and molecular oxygen to produce a burst of oxygen radicals with reperfusion of the ischemic bowel. Evidence implicating oxygen radicals in inflammatory disorders of the digestive tract (i.e., pancreatitis), radiation injury, and hepatic cirrhosis is also presented. The available data suggest that oxygen radicals appear to be a fundamental mechanism of tissue injury in the pathogenesis of various disorders of the digestive system.
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PMID:Role of oxygen-derived free radicals in digestive tract diseases. 635 11


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