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

Acetaldehyde (AA), the first product of ethanol metabolism, has been suggested as an important mediator in alcoholic pancreatitis, but experimental evidence has not been convincing. Prior work using the isolated perfused canine pancreas preparation has suggested that toxic oxygen metabolites generated by xanthine oxidase (XO) may mediate the early injury in pancreatitis. Xanthine oxidase is capable of oxidizing AA, and during this oxidation free radicals are released. The hypothesis that acute alcoholic pancreatitis may be initiated by AA in the presence of active XO (converted from xanthine dehydrogenase [XD]) was tested in the authors' experimental preparation by converting XD to XO by a period of ischemia, and infusing AA. Control preparations remained normal throughout the 4-hour perfusion (weight gain, 7 +/- 4 g; amylase activity, 1162 +/- 202 U/dL). One hour of ischemia or infusion of AA at 25 mg/hr or at 50 mg/hr without ischemia did not induce changes in the preparation. Acetaldehyde at 250 mg/hr induced minimal edema and weight gain (16 +/- 4 g; p less than 0.05), but not significant hyperamylasemia. Changes also were not observed when 1-hour ischemia was followed by a bolus of ethanol (1.5 g) or sodium acetate (3.0 g), or by infusion of 25 mg/hr of AA. One hour of ischemia followed by infusion of AA at 50 mg/hr or at 250 mg/hr induced edema, hemorrhage, weight gain (22 +/- 7 g [p less than 0.05] and 26 +/- 17 g [p less than 0.05]) and hyperamylasemia (2249 +/- 1034 U/dL [p less than 0.05] and 2602 +/- 1412 U/dL [p less than 0.05]). Moreover infusion of AA at 250 mg/hr after 2 hours of ischemia potentiated the weight gain (62 +/- 20 g versus 30 +/- 14 g [p less than 0.05]), but not the hyperamylasemia (3404 +/- 589 U/dL versus 2862 +/- 1525 U/dL) as compared with 2 hours of ischemia alone. Pancreatitis induced by 1 hour of ischemia followed by AA at 50 mg/hr could be inhibited by pretreatment with the free radical scavengers superoxide dismutase and catalase and ameliorated with the XO inhibitor allopurinol. The authors conclude that AA, in the presence of active XO, can initiate acute pancreatitis in the isolated canine pancreas preparation and may be important in the initiation of acute alcoholic pancreatitis in man. Toxic oxygen metabolites appear to play an important intermediary role.
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PMID:The role of acetaldehyde in the pathogenesis of acute alcoholic pancreatitis. 172 Jun 11

Vascular mechanisms play an important but controversial role in the pathogenesis of acute pancreatitis. In experimental animals, injection of wax, powder, air, mercury, and microspheres into the pancreatic artery causes pancreatitis by end artery occlusion with resulting cellular infarction. Larger microspheres do not cause pancreatitis because collateral blood flow is preserved. Clinical evidence, such as microthrombi and atheromatous emboli in the pancreatic artery of patients with pancreatitis, supports pancreatic infarction as an etiologic agent. Experimental and clinical studies have suggested that pancreatic ischemia may also cause pancreatitis, but these studies have not been conclusive. We have compared five hours of total occlusion of the pancreaticoduodenal artery along with four hours of reperfusion to bile injection into the pancreatic duct as causes of pancreatitis. Bile injection caused a significant increase in serum amylase, activation of trypsin in pancreatic exudate, and histologic evidence of necrotizing pancreatitis. Pancreatic blood flow decreased as pancreatitis developed. Ischemia for five hours did not cause a significant increase in serum amylase or activation of trypsin in pancreatic exudate. Only edema was seen histologically, but there was no necrosis. Pancreatic blood flow increased with reperfusion. We believe ischemia aggravates, but does not initiate pancreatitis. Ischemia does not induce inflammation and necrosis in the pancreas, although infarction does.
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PMID:Mechanisms of acute pancreatitis. Vascular etiology. 174 44

In order to examine the toxic effects on the pancreas of oxygen free radicals which are generated at reperfusion after ischemia, a short term-ischemia/reperfusion model was prepared in rats. Both the anterior mesenteric artery and the celiac artery were ligated and then released to restore blood flow. In a group where the anterior mesenteric and the celiac arteries were ligated for 60 minutes, the serum levels of amylase and lipase rose 7 and 6 times, respectively, 7 hours after reperfusion. In a group ligated for 30 minutes, both levels remained unchanged. Histologically, vacuolization of the pancreatic acinar cells was observed, only in a group rats ischemic for 7 hours. In rats ligated for 60 minutes with a continuous venous infusion of superoxide dismutase (SOD) (3600 U/Kg/hour), the secretion of amylase and lipase decreased to 25 percent of that in the non-injected group. These results confirm that the oxygen free radicals, which are generated by the short term-ischemia/reperfusion method, injure the pancreas. This may lead to pancreatitis with hyperamylasemia and hyperlipasemia. Pretreatment with an active oxygen scavenger, SOD, markedly reduces the rise in serum amylase and lipase levels. This suggests that active oxygen free radicals are involved in the pathogenesis of acute pancreatitis.
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PMID:[Effect of short-term-ischemia and reperfusion on the rat pancreas]. 182 5

In this article, the evidence for the involvement of free radicals in some of the gastrointestinal disorders is reviewed. Oxygen radicals are partially reduced oxygen species that include superoxide, and hydroxyl radicals, and hypophthalous acids. Most cells possess numerous antioxidant enzymes and scavengers to protect themselves from these injurious agents; the rate of production of reactive oxygen metabolites may exceed the capacity of the antioxidant defenses thus resulting in tissue damage. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of oxygen radicals. Sources of radicals in the gastrointestinal tract include mucosal xanthine oxidase and NADPH oxidase found in the resident phagocytotic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. Other sources of oxygen radicals in the gastrointestinal tract involve ischemia and reperfusion, drug ingestion, diet and radiation therapy. Recent studies have demonstrated the involvement of oxygen radicals following active episodes of small-intestinal ischemia, ulcerative colitis, pancreatitis and gastric ulcer. In contrast to cell antioxidants, control of tissue free radical levels is now pharmacologically feasible and perhaps justified for specific diseases. However, carefully designed and controlled clinical trials are needed.
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PMID:Oxygen radicals: their role in selected gastrointestinal disorders. 186 20

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

Five patients with severe acute pancreatitis (AP) underwent subtotal pancreatectomy, and six patients with advanced chronic pancreatitis (CP) were subjected to pancreatic resection. Microangiography and histological studies were performed on the resected pancreata. All patients with AP had histologically verified necrotizing pancreatitis. Pancreatic ducts in the necrotic areas had severe inflammation in their walls and a decrease in their vascularity. The ductal walls of CP patients were indistinguishable from the surrounding fibrosis and the vascular supply of the ducts was markedly diminished. The vessels were reduced in number, and their calibers varied considerably. Ductal ischemia in connection with AP and CP is discussed.
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PMID:Vascular changes of pancreatic ducts and vessels in acute necrotizing, and in chronic pancreatitis in humans. 203 15

We reviewed the transpulmonary gradient, pulmonary arterial systolic pressure, pulmonary vascular resistance (Wood units), and pulmonary vascular resistance index (Wood units X Body surface area), recorded preoperatively in 109 recipients aged 44.6 +/- 13.5 (mean +/- SD) years who underwent orthotopic heart transplantation between March 1984 and March 1988, to identify which measure of pulmonary hypertension most accurately predicts poor outcome after orthotopic heart transplantation. These recipients were followed up as many as 57 (24.7 +/- 14.5) months after their transplant procedure. Preoperative hemodynamic values were as follows: transpulmonary gradient, 10.4 +/- 4.7 mm Hg; pulmonary artery systolic pressure, 53.6 +/- 14.8 mm Hg; pulmonary vascular resistance, 2.7 +/- 1.8 Wood units; pulmonary vascular resistance index, 4.9 +/- 2.7. Nineteen recipients died within 1 year after orthotopic heart transplantation. Causes of death were acute rejection (8), chronic rejection (1), infection (2), nonspecific orthotopic heart transplant failure (4), bowel ischemia (1), pancreatitis (1), lymphoma (1), and liver failure (1). Preoperative pulmonary arterial systolic pressure, pulmonary vascular resistance, and pulmonary vascular resistance index were not predictive of 1-month, 6-month, or 1-year mortality. One-month mortality rates of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg and of those with transpulmonary gradient less than 12 mm Hg were not significantly different (11% vs 3%; p = 0.12). The 6-month mortality rate of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg, however, was five times greater than that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (24% vs 5%; p = 0.003), and 12-month mortality of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg was increased sevenfold when compared with that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (36% vs 5%; p = 0.0005). These results suggest that presently used measures of pulmonary hypertension do not predict mortality in the first month after orthotopic heart transplantation, but that elevated preoperative transpulmonary gradient is associated with a significant increase in mortality at 6 and 12 months after orthotopic heart transplantation. Prospective randomized trials are needed to determined whether extended preload and afterload reduction before and/or after transplant will favorably influence long-term prognosis of orthotopic heart transplant recipients with elevated preoperative transpulmonary gradient.
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PMID:Influence of preoperative transpulmonary gradient on late mortality after orthotopic heart transplantation. 223 Oct 91

The early lesions induced in the pancreas of dogs by the intraductal injection of bile-trypsin were studied. Histological, histochemical and electron microscopic techniques were used. The primary lesions analyzed thirty three minutes after the induction of pancreatitis consisted in cell alterations, blood stasis and oedema. At first, the affected acinar cells showed enlargement of the rough endoplasmic reticulum cisternae, later they were disrupted and then appeared vesicles with ribosomes adhering to the external surface. Mitochondria were swelled and showed cristae disrupted which finally appeared destroyed. The zymogen granules lost density, decreased in size and number and later disappeared, Ducts maintained the normal structure and their cells were still observed in areas where the tissue was greatly destroyed. the results obtained suggest that: 1) The experimental acute pancreatitis induced by bile-trypsin is characterized by primary and severe damage in the acinar cells, with secondary ischemia due to stasis and intravascular coagulation. 2) Cellular rests and probably endogenous enzymes invade the periacinar spaces, then would penetrate into the vascular system producing the generalization of lesions.
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PMID:[Acute pancreatitis induced by bile trypsin: structural and ultrastructural study]. 227 10

Acute pancreatitis was initiated in the isolated ex vivo, perfused canine pancreas preparation by exposing the gland to a 2 hour period of ischemia before a 4 hour perfusion period. The pancreatitis was manifested by edema formation, weight gain, and hyperamylasemia. When the osmotically active agent albumin was added to the perfusate at the end of the ischemic period, virtually no edema developed, weight gain was minimal, and the amylase level remained within normal limits during the subsequent 4 hour perfusion period. This suggests that a change in capillary permeability may be an early step in the pathogenesis of ischemia-induced pancreatitis in this experimental model.
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PMID:Experimental ischemic pancreatitis: treatment with albumin. 241 56

Normothermic ischemia tolerance is an important aspect of organ procurement and transplantation. The function of pancreas and kidney autografts was investigated in totally pancreatectomized or nephrectomized canine recipients. In 30 dogs the left limb (tail) of the pancreas was removed but left in the abdominal cavity after cessation of blood flow to produce warm ischemia for 30, 60, and 120 min (10 dogs at each time point), and then was flushed with cold Ringers' lactate and transplanted to the iliac vessels. Twenty dogs with fresh pancreatic transplants were controls. The success rate of pancreas transplants with warm ischemia of 1/2 and 1 hr was the same as that of controls (80%); however, after 1 hr normothermia 5/10 dogs had episodes of hyperglycemia for 1 week before glucose levels came back to normal. All but one graft with 2 hr warm ischemia failed. Intravenous glucose tolerance test (IVGTT) mean (+/- SEM) K values were not different in the successful groups, i.e., no warm ischemia: -1.55 +/- 0.15%; 1/2 hr warm ischemia: -1.81 +/- 0.18%; 1 hr warm ischemia: -1.64 +/- 0.09%. Amylase levels increased after transplant with maximum values at Day 2, then returned to normal, but the levels remained elevated in recipients of grafts subjected to longer normothermia with evidence of pancreatitis after 1 hr warm ischemia. Fifteen kidney grafts were treated similarly with warm ischemia exposure of 1/2 hr (n = 9) and 1 hr (n = 6) before being flushed and autotransplanted, and were compared to 16 fresh kidney transplants. After 1/2 hr warm ischemia none of the kidney grafts failed but 78% of the recipients had elevated serum creatinine and urea nitrogen levels which returned slowly to normal after 3 to 4 weeks. There was only one long-term survivor after 1 hr warm ischemia. Thus the pancreas seems to be more resistant to warm ischemia damage than is the kidney. This difference should be taken into consideration in regard to organ procurement for clinical transplantation.
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PMID:Definition of normothermic ischemia limits for kidney and pancreas grafts. 242 97


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