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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of unexplained pancreatitis in patients dying after cardiac operations has been recorded as 16%, with evidence to implicate ischemia in the pathogenesis of the pancreatitis. Increased amylase--to--creatinine clearance ratios (ACCR), suggesting pancreatic dysfunction, have been reported in patients following nonpulsatile cardiopulmonary bypass (CPB). Pulsatile CPB is increasingly recognized to be a more physiological form of perfusion, particularly with respect to capillary blood flow. In this study the ACCR has been determined before, during, and after cardiac operations performed with both nonpulsatile and pulsatile CPB. Twenty patients undergoing elective cardiac operations were studied. Ten patients had nonpulsatile CPB (nonpulsatile group) and 10 had pulsatile CPB (pulsatile group). The two groups were comparable as regards perioperative variables and perfusion parameters. In both groups the ACCR was estimated preoperatively, on three occasions during the operation, and daily on the first 5 postoperative days. A significant elevation in ACCR was observed in nine of 10 patients in the nonpulsatile group but in only one of 10 patients in the pulsatile group (p less than 0.001). The significant improvement of ACCR stability following pulsatile CPB may indicate that this form of perfusion will reduce the risk of pancreatitis following cardiac operations performed with CPB.
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PMID:The amylase-creatinine clearance ratio following cardiopulmonary bypass. 616 15

Recent clinical studies have suggested that ischemia may be an important factor in the pathogenesis of acute pancreatitis. The effects of ischemia on the pancreas were investigated utilizing the isolated perfused canine pancreas. Six control glands were perfused with autologous blood with an arterial Po2 ranging from 250 to 350 mm Hg. During the 4-hour perfusion period, gross appearance remained normal, weight gain was minimal (7 gm), and mean amylase levels (853 Caraway units [CU]/dl) remained within normal limits (less than or equal to 1,000 CU/dl). Lowering the arterial Po2 (range 30 to 60 mm Hg) in six glands while maintaining the flow at control levels elicited no significant change. Similarly, decreasing the flow (25% of control) with the arterial Po2 at 250 to 350 mm Hg produced no significant change in gross appearance, weight gain, or mean amylase levels. Combining low flow and low arterial Po2 in six glands also elicited no significant change as compared with controls. Four glands were subjected to total ischemia for 1 hour before being perfused. The glands became hyperemic, but mean weight gain (13 gm) and mean amylase levels (740 CU/dl) wee similar to those of controls. In contrast, in six glands subjected to total ischemia for 2 hours gross edema developed during the subsequent 4-hour perfusion. Mean weight gain (52 gm) and mean amylase levels (1,825 CU/dl) were significantly higher than in controls. These experimental data demonstrate that in the isolated perfused canine pancreas severe ischemia can produced significant injury. They therefore support the hypothesis that ischemia can clinically initiate acute pancreatitis.
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PMID:The role of ischemia in acute pancreatitis: studies with an isolated perfused canine pancreas. 617 32

Samples of intestinal contents were obtained from 16 patients: 5 from the midjejunum, 10 from the distal ileum, and 1 from the cecum. The presence of pancreatic and nonpancreatic isoamylases in these fluids was evaluated by an inhibitor assay (Pharmacia Corporation) and by polyacrylamide gel electrophoresis. In every sample the inhibitor assay detected the presence of pancreatic-type isoamylase but not salivary-type isoamylase. Electrophoresis confirmed that salivary-type isoamylase was totally absent. Therefore, in intestinal disorders which disrupt the intestinal mucosal barrier (such as ischemia, perforation, ulceration, or obstruction), the amylase which escapes from the intestinal lumen and is reabsorbed into the circulation is likely to consist entirely of pancreatic-type isoamylases. In these circumstances, measurement of serum amylase isoenzymes will not distinguish acute pancreatitis from an acute intraabdominal catastrophe requiring surgery.
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PMID:Identification of amylase isoenzymes in intestinal contents. 620 Feb 78

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 interrelationships between hemodynamics and hypoglycemia during the course of endotoxin shock (ES) has not been fully defined. In the following study, ES (E. coli, 1 mg/kg; n = 7) was induced in a canine model and systemic hemodynamics, glucose metabolism, and hepatic and pancreatic function monitored for 5 hr and compared to time-matched controls (TMC, n = 7). Total peripheral resistance (TPR, dynes-sec-cm-5) increased from 3227 +/- 430 to 4050 +/- 750 at 30 min and then declined to 3050 +/- 1100 at 90 minutes. TPR progressively increased to 6225 +/- 749 by 5 hours. Plasma glucose did not significantly differ from control values (105 +/- 4 mg%) for the first 90 min but then declined to 68 +/- 6 mg% at 4.5 hours. (TMC = 103 +/- 17, P less than 0.05). Serum amylase during the 5 hr protocol was not elevated (TMC = 110.9 +/- 2.4; ES = 100 +/- 1.97%; P greater than 0.1), and light microscopy of the exocrine pancreas demonstrated normal acinar structure. Islet cell structure from the ES group is not significantly different from the TMC. Hepatic histology in the ES group demonstrated periportal and perilobular degranulation and hepatocyte disruption not seen in the TMC. It is hypothesized that ES results in a circle of positive feedback initiated by an increase in TPR and subsequent decrease in flow resulting in hepato-pancreatic ischemia. Ischemic damage is most apparent at the liver and leads to changes in hepatic metabolic activities which contribute to the developing hypoglycemia of the late phase of ES.
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PMID:Hemodynamics, hypoglycemia, and hepato-pancreatic pathology during the course of endotoxin shock. 734 83

In an examination of the effect of ischemia and reperfusion on the generation of active oxygen species during pancreatic cell damage, a short-term ischemia and reperfusion model was prepared by the occlusion and reperfusion of both the anterior mesenteric artery and the celiac artery in rats. Following 60 minutes of occlusion plus 7 hours of reperfusion of the anterior mesenteric artery and the celiac artery, the serum concentrations of amylase and lipase rose significantly to 7 and 6 times the respective control values. After 30 minutes of occlusion plus 7 hours of reperfusion, or after 7 hours of occlusion without reperfusion, amylase and lipase levels were not changed significantly. The continuous intravenous infusion of superoxide dismutase (3600 U/kg/hour) in rats receiving 60 minutes of occlusion plus 7 hours of reperfusion suppressed the rise in serum amylase and lipase values to 25 percent of the values in the non-injected group. These results suggest that the active oxygen species which are generated by the short-term ischemia and reperfusion method injure the endothelium and cause hyperamylasemia and hyperlipasemia. Inhibition of the rise in serum amylase and lipase concentrations by pretreatment with a scavenger of active oxygen, superoxide dismutase, suggests that the active oxygen species are involved in the pathogenesis of acute pancreatitis.
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PMID:Effect of postischemic reperfusion on the pancreas. 750 64

The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia-reperfusion injury of the pancreas were evaluated using an isolated in-vivo-perfused dog pancreas model. Pancreatic endocrine and exocrine function were stimulated with cholecystokinin octapeptide (10(-12) mol). This dose significantly increased endogenous prostaglandin I2 and thromboxane A2 production by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a decrease of insulin release (P < 0.01). There was also a decrease of pancreatic juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting damage to the acinar, ductular, and beta cells. Intravenous administration of ONO 3708 (200 micrograms/kg/min) throughout the experiment prevented these abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the peroxidation of cell membrane lipids and by decreasing the thromboxane A2/prostaglandin I2 ratio, which is a predictor of cellular injury.
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PMID:The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia-reperfusion injury of the dog pancreas. 750 45

An experimental model of chronic pancreatitis was produced by a chronic ischemia which was induced by ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery. Macroscopic findings at 3 and 6 months after model preparation showed that the pancreas was hard, with severe inflammatory change. In the secretin-cerulein test at 3 and 6 months, the flow rate of pancreatic juice, amylase output and bicarbonate concentration were significantly reduced as compared with the controls. The histopathological findings consisted of a decrease in the pancreatic parenchyma, replacement of fat, severe inflammatory cell infiltration, extensive fibrosis and tubular complexes. As this model closely resembles human chronic pancreatitis, we conclude that ischemia is an etiological factor in chronic pancreatitis.
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PMID:Canine model of chronic pancreatitis due to chronic ischemia. 751 52

The effect of hydroxyethyl starch on pancreas preservation with cardioplegic histidine-tryptophan-ketoglutarate solution (HTK) was investigated. The study was performed using an in vitro reperfusion system of the porcine pancreas. During organ preservation pancreatic weight, arterial pressure, volume flow, and washout of amylase and lactate were quantified. Addition of hydroxyethyl starch did not affect arteriovenous volume flow or washout of amylase and lactate during protective perfusion after pancreas preparation. However, hydroxyethyl starch in HTK prevented an increase in pancreatic weight at the end of the protective perfusion (102.2 +/- 4.55% vs 127.8 +/- 4.62% in controls; p < 0.005) and after 24 h cold ischemia (72.9 +/- 3.91% vs. 83.5 +/- 3.49% in controls; p < 0.05). Hydroxyethyl starch did not affect postischemic organ quality assessed during reperfusion in a perfusion chamber by pancreatic vascular resistance, amylase and lactate release, insulin secretion, and oxygen consumption. We conclude that hydroxyethyl starch does not bring about any further improvement in immediate postischemic organ quality assessed in an in vitro reperfusion system.
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PMID:Hydroxyethyl starch does not improve pancreas preservation with HTK. 768 42

Four models of acute pancreatitis have been previously developed that use the ex vivo perfused isolated canine pancreas preparation. The four models include the intraarterial infusion of oleic acid (FFA) that mimics hyperlipemic pancreatitis, partial obstruction of the pancreatic duct with secretin stimulation (POSS) that mimics gallstone pancreatitis, a 2-hour period of ischemia before perfusion (ISCH 2) that mimics shock pancreatitis, and the infusion of cerulein at supramaximal stimulatory doses (CER), which lacks an obvious clinical counterpart. In the FFA, POSS, and ISCH 2 pancreatitis, but not in the CER pancreatitis, toxic oxygen metabolites, generated by the enzyme xanthine oxidase (XO), have been shown to be important mediators in the early pathogenesis. Ordinarily XO primarily occurs as xanthine dehydrogenase (XD) but can be converted to XO, which is the form that generates toxic oxygen metabolites. This conversion of XD to XO may take place either reversibly by way of sulfhydryl group oxidation or irreversibly by means of proteolytic cleavage of XD. This study was undertaken to investigate the mechanism of conversion of XD to XO in the FFA-, POSS-, and ISCH 2-induced pancreatitis models. CER pancreatitis was studied for comparison. After 4 hours of perfusion, pancreatitis was manifest by edema, weight gain, and hyperamylasemia in all four models. Dithiothreitol, a sulfhydryl group protector, ameliorated the weight gain in the FFA (40 +/- 14 gm to 18 +/- 13 gm; p < 0.05), POSS (28 +/- 10 gm to 9 +/- 3 gm; p < 0.05), and ISCH 2 pancreatitis (30 +/- 13 gm to 15 +/- 3 gm; p < 0.05), and ameliorated the hyperamylasemia in the POSS pancreatitis (12,062 +/- 4304 units/dl to 5877 +/- 2659 units/dl; p < 0.05). The CER pancreatitis was not ameliorated with dithiothreitol. A serine protease inhibitor of low molecular weight, phenylmethylsulfonyl fluoride, ameliorated only the CER pancreatitis (weight gain from 28 +/- 10 gm to 17 +/- 10 gm, p < 0.05; amylase activity from 38,116 +/- 6491 units/dl to 23,372 +/- 11,654 units/dl, p < 0.05), and not the FFA, POSS, or ISCH 2 pancreatitis. We conclude that in the three models of pancreatitis (FFA, POSS, and ISCH 2) that are mediated by toxic oxygen metabolites, XD is converted to XO reversibly by way of sulfhydryl group oxidation rather than irreversibly by way of proteolysis. In the CER pancreatitis, where XO does not play a role in the pathogenesis, proteolytic enzymes may be important mediators in the injury.
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PMID:The mechanism of conversion of xanthine dehydrogenase to xanthine oxidase in acute pancreatitis in the canine isolated pancreas preparation. 841 95


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