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)

Somatostatin and its stable analogue octreotide are proposed to ameliorate the outcome from acute pancreatitis by inhibiting pancreatic secretion and preventing cell injury. This study investigated the effect of somatostatin analogue octreotide on pancreatic microcirculatory injury (by means of intravital fluorescence microscopy) and enzyme release after ischemia/reperfusion of the pancreas in rats. Octreotide, injected 15 min before the end of 2 h of ischemia as a bolus injection (50 micrograms kg-1 i.v.) or as a continuous infusion (50 micrograms kg-1 h-1 i.v.), attenuated postischemic reperfusion injury of the pancreas as evidenced by a significant (p < 0.05) improvement in capillary perfusion and decrease in leukocyteendothelium interaction in postcapillary venules compared to ischemia without treatment. Pancreas amylase concentration remained unchanged in the octreotide group but increased significantly (p < 0.05) in the ischemia group. These results indicate a protective effect of octreotide against postischemic reperfusion injury of the pancreas in rats.
Pancreas 1996 Apr
PMID:Protective effect of the somatostatin analogue octreotide in ischemia/reperfusion-induced acute pancreatitis in rats. 883 Mar 36

We have shown that 5-hr preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C allows ATP synthesis and makes it possible to resuscitate a canine pancreas subjected to 90 min of warm ischemia. However, 8 hr of preservation using this method caused a disturbance of vascular microcirculation and did not resuscitate the grafts. The aim of this study was to examine the effect of thromboxane A2 synthesis inhibitor OKY046 on vascular endothelial cells and ATP tissue levels of canine pancreas during preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C, and vascular microcirculation and pancreas viability after transplantation. Graft viability was judged by graft survival following autotransplantation. ATP tissue levels were measured by high-performance liquid chromatography at the end of preservation. Viability of the vascular endothelial cells was judged using nuclear trypan blue uptake of the graft after preservation. Pancreatic tissue perfusion was measured using an H2 clearance technique after reperfusion. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5). However, 5-hr preservation made it possible to recover the pancreas (5/5); 8-hr preservation was not successful (0/3). ATP tissue levels after 5-hr and 8-hr preservation were 9.40+/-2.09 and 7.37+/-1.06 micromol/g dry weight, respectively, and OKY046 did not affect ATP synthesis during 8-hr preservation (8.44+/-0.92 micromol/g dry weight). The percentage of nuclear trypan blue uptake of endothelial cells in 8-hr-preserved grafts was 37.6+/-11.6% and was significantly higher than the value in 5-hr-preserved grafts (5.0+/-3.0%; P<0.01). However, OKY046 significantly reduced trypan blue uptake in 8-hr-preserved grafts (8.2+/-3.6%; P<0.01). Pancreatic tissue perfusion in 8-hr-preserved grafts after 2 hr of reperfusion was 28.5+/-7.5 ml/min/100 g, and was significantly lower than the value in 5-hr-preserved grafts (57.1+/-4.4 ml/ min/100 g; P<0.01), but OKY046 dramatically improved pancreatic tissue perfusion (97.1+/-14.6 ml/min/100 g; P<0.01). As a consequence, 8-hr-preserved grafts were resuscitated (4/5). We conclude that OKY046 protects the vascular endothelium during preservation by the two-layer method at 20 degrees C and consequently improves vascular microcirculation on reperfusion. Together with ATP synthesis, which is essential for repairing damaged cells, the canine pancreas graft subjected to 90 min of warm ischemia is resuscitated during 8-hr preservation by the two-layer method at 20 degrees C. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.
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PMID:Extending the margin of safety of preservation period for resuscitation of ischemically damaged pancreas during preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C with thromboxane A2 synthesis inhibitor OKY046. 887 77

The role of nitric oxide in lipoxygenase metabolism after a process of ischemia-reperfusion in pancreas transplantation has been evaluated in this study. Sprague-Dawley rats were randomized into three groups, as follows: Group I--Control animals not surgically manipulated; Group II.--Pancreas transplantation, after 12 h of organ preservation; Group III.--Same as II but with administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) (10 mg/Kg) prior to organ revascularization. The results show post-transplantation increases in leukotriene B4 and 12-hydroxyeicosatraenoic acid levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in 12-hydroxyeicosatetraenoic acid, but was unable to modify leukotriene B4 increases suggesting the existence of a direct effect of nitric oxide on the 12-lipoxygenase metabolism in pancreas transplantation.
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PMID:Nitric oxide enhances 12-HETE versus LTB4 generation in pancreatic transplantation. 892 46

Pancreatic hyperstimulation with simultaneous duct obstruction does not cause the typical features of acute pancreatitis, therefore the role of an additional challenge, such as either ethanol intoxication or short-term ischemia, was studied. Alcoholic pancreatitis was induced in 28 rats by acute ethanol intoxication (0.25 LD50) and an obstruction/hyperstimulation mechanism (clip of the biliopancreatic duct for 20 min and intravenous stimulation with 5 U of cholecystokinin and secretin each). Ischemic pancreatitis was performed by obstruction/hyperstimulation and subsequent pancreatic ischemia by clamping the supplying arteries for 40 min. The macro- and microscopic alterations were evaluated and graded by a scoring system. Additionally, the pancreas was removed in 50% of the animals and the pancreatic acini were prepared. From those acini the intracellular enzymes trypsinogen, kallikreinogen, amylase, lipase, glucuronidase, and acidic phosphatases were determined. While obstruction/hyperstimulation, 40 min of ischemia, or ethanol alone did not induce acute pancreatitis, a combination of obstruction/hyperstimulation with either ethanol or ischemia resulted in acute pancreatitis in 68 and 60% of treated rats, respectively. Similarly, both models were characterized by extrapancreatic fat necrosis and acinar necrosis at the periphery of the lobules. Almost all intracellular enzymes were elevated in both pancreatitis models compared to sham-operated controls. Both alcohol and ischemia were insults that sensitize the pancreas to develop acute pancreatitis after obstruction/hyperstimulation. Since the observed morphologic and enzymatic alterations in both models are very similar, alcohol and ischemia might have some common pathways by which they make the pancreas vulnerable to enzymatic attacks.
Pancreas 1997 Jan
PMID:Similar morphological and intracellular biochemical changes in alcoholic acute pancreatitis and ischemic acute pancreatitis in rats. 898 5

We have shown that 24 to 48 hour-preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) method at 4 degrees C resuscitates a canine pancreas subjected to 90 min of warm ischemia. However, it is necessary to shorten preservation period for resuscitation of the ischemically damaged pancreas in a clinical simultaneous pancreas-kidney transplantation. The purpose of this study was to clarify the effect of preservation temperature and period on the resuscitation of the ischemically damaged pancreas during preservation by the two-layer method. First of all, we examined the possibility of resuscitation of the ischemically damaged pancreas during short-term preservation by the two-layer method. After 90 minutes of warm ischemia, canine pancreases were preserved by the two-layer method at 4, 20, or 37 degrees C. In control group, the pancreas graft was autotransplanted without preservation. Graft viability was judged by graft survival after autotransplantation. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5). At 4 degrees C, 5 to 12 hr-preservation did not resuscitate the grafts (0/3 and 0/3 respectively). At 20 degrees C, 3 and 5 hr-preservation resuscitated the grafts (3/5 and 5/5 respectively), although 1 and 8 hr-preservation were not successful (0/3 and 0/3 respectively). At 37 degrees C, all the grafts were not resuscitated irrespective of preservation period. It was clear that the ischemically damaged pancreas was resuscitated during shot-term preservation by the two-layer method only at 20 degrees C. Secondly, we measured tissue adenine nucleotide levels by high performance liquid chromatography and pancreatic tissue perfusions using H2 clearance technique on reperfusion and examined the viability of vascular endothelium by nuclear trypan blue staining to make clear the necessary conditions for resuscitation of the ischemically damaged pancreas at 20 degrees C. ATP tissue levels in one hr-preserved grafts were 2.55 +/- 0.38 mumol/g dry weight and were significantly lower compared with the levels in 5 and 8 hr-preserved grafts, 9.40 +/- 2.09 (P < 0.01) and 7.37 +/- 1.06 mumol/g dry weight (P < 0.01) respectively. On the other hand, nuclear trypan blue uptakes of endothelial cells in 8 hr-preserved grafts were 37.6 +/- 11.6% and were significantly higher than 1 hr- and 5 hr-preserved grafts 5.6 +/- 4.5 (P < 0.01) and 5.0 +/- 3.0% (P < 0.01) respectively. As a consequence, pancreatic tissue perfusions in 8 hr-preserved grafts, 31.0 +/- 3.5 ml/min/g, were significantly lower than 1 hr- and 5 hr-preserved graft 72.0 +/- 11.6 (P < 0.01), 63.9 +/- 13.3 ml/min/g (P < 0.01) respectively. However, thromboxane A2 synthesis inhibitor (OKY046 0.1 mM/L) decreased the percentage of trypan blue uptake (8.2 +/- 3.6%) without interfering ATP synthesis (8.44 +/- 0.92 mumol/g dry weight) in 8 hr-preserved pancreas and tissue perfusions after reperfusion were dramatically improved (99.6 +/- 11.8 ml/min/g). As a result the ischemically damaged pancreas was resuscitated (4/5, 80%). It was suggested that 1 hr-preservation was not enough to synthesize ATP, which was essential to repair damaged cells, although vascular endothelial cells were maintained. Eight hr-preservation incurs endothelial cell damage although ATP tissue levels were maintained and consequently microcirculation was disturbed at reperfusion but OKY046 protects endothelial cells against preservation/reperfusion injury. As a consequence, the ischemically damaged pancreas was resuscitated. We conclude that short-term (3 to 8 hr) preservation at 20 degrees C by the two-layer method with OKY046 accelerates ATP synthesis, which is essential for repairing damaged cells and protects microvascular endothelial cells. This makes it possible to resuscitate the canine pancreas graft subjected to 90 min warm ischemia. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.
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PMID:The effect of preservation temperature and period on resuscitation of the ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) method. 898 26

The role of endothelin and its relationship with nitric oxide (NO) production in ischemia-reperfusion associated with pancreas transplantation has been explored. For this purpose, pancreatic levels of endothelin were evaluated in an experimental model of pancreas transplantation after different periods of cold preservation. The effects of NO synthase inhibition were also evaluated. Results show posttransplantation increases in lipase and endothelin production. The release of lipase and endothelin was only prevented by NG-nitro-L-arginine methyl ester after a short ischemic period. Thus, endothelin synthesis could be a consequence of stimulation with NO in the ischemia-reperfusion associated with pancreas transplantation.
Pancreas 1997 May
PMID:Nitric oxide enhances endothelin production in pancreas transplantation. 916 83

Recent evidence has suggested that ischemia-reperfusion injury is fundamental to the pathogenesis of acute pancreatitis. This study was designed to determine whether acute pancreatitis is associated with elevated serum manganese superoxide dismutase (MnSOD), a key antioxidant enzyme, considered a marker of ischemia-reperfusion injury in myocardial infarction. Thirty-four patients with acute pancreatitis had measurements of MnSOD on days 0, 2, and 5 after recruitment. The patients were recruited within 12 h of admission to hospital and had measurements of MnSOD on days 0, 2, and 5. Patients with severe acute pancreatitis had significantly elevated serum MnSOD concentrations on days 2 and 5 compared with patients with mild acute pancreatitis, but not on the day of recruitment. Elevated serum MnSOD correlated with peripheral plasma markers of lipid peroxidation (malondialdehyde) and neutrophil activation (myeloperoxidase) and was associated with decreased plasma ascorbic acid concentrations. The serial measurement of serum MnSOD may prove useful as a marker of the effectiveness of treatment designed to limit ischemia-reperfusion injury in patients with severe acute pancreatitis.
Pancreas 1997 Jul
PMID:Manganese superoxide dismutase: a marker of ischemia-reperfusion injury in acute pancreatitis? 921 96

We studied the pancreatic high-energy phosphates in two models of acute pancreatitis using 31P nuclear magnetic resonance (NMR) in rats for the first time in vivo. Alcoholic pancreatitis was induced by acute ethanol intoxication and an obstruction-hyperstimulation mechanism. Taurocholate pancreatitis was generated by intraparenchymal administration of 1 ml of 1-10% taurocholate-Na+. In addition to the obligate control groups, a simple ischemia experiment was performed. The high-energy phosphates were monitored by 31P NMR spectroscopy at 2.0 T. Additionally, by means of a scoring system, the quality and quantity of pathomorphologic parameters were quantified after 24 h. 31P spectra acquired after injection of taurocholate showed an increase in inorganic phosphate with a concomitant decrease in ATP levels, similar to pancreatic ischemia. This irreversible decrease was accompanied histologically by severe pancreatic hemorrhage. After induction of alcoholic acute pancreatitis a reversible decrease in ATP was occasionally seen. Even when alcoholic pancreatitis had been fully established at 24 h, the 31P NMR spectrum was normal in all animals. In conclusion, depletion of high-energy phosphates seems to occur as a result of pancreatic cell death rather than being a cause of pancreatic necrosis. For the first time we applied in vivo NMR in the rat pancreas to study the time course in acute pancreatitis.
Pancreas 1997 Nov
PMID:Different changes in high-energy phosphates in alcoholic acute pancreatitis and taurocholate acute pancreatitis in rats using NMR spectroscopy at 2.0 T. 936 Oct 88

Reperfusion injury after pancreas transplantation is a cause of early graft pancreatitis. The aim of this study was to quantify pancreatic microcirculation after pancreas transplantation in correlation with cold ischemia time. In a second step the effect of N-acetylcysteine on reperfusion damage was tested. Pancreas transplantation was performed in three different groups of male Lewis rats. Groups 1 and 2 received no special treatment. Cold ischemia time was 1.5 hours in group 1 and 16 hours in groups 2 and 3. In group 3 donor and recipient were both treated with N-acetylcysteine (300 mg/kg) 1.5 hours after reperfusion graft microcirculation was quantified by means of intravital microscopy. Rhodamine-labeled leukocytes, fluoroscein isothiocyanate-labeled erythrocytes, and fluoroscein isothiocyanate-albumin were used as fluorochromes. After a cold ischemia time of 16 hours, functional capillary density, erythrocyte velocity, and leukocyte-endothelium interaction were reduced significantly compared to a cold ischemia time of 1.5 hours (P<0.05). After 16 hours of cold ischemia, treatment with N-acetylcysteine improved all of these parameters (P</=0.05). Ischemia/reperfusion injury after experimental pancreas transplantation is characterized by a disturbance of the pancreatic microcirculation exhibiting a correlation with the duration of cold ischemia. Treatment of donor and recipient with N-acetylcysteine resulted in prevention of cold ischemia-induced microcirculatory disturbance.
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PMID:Characterization and reduction of ischemia/reperfusion injury after experimental pancreas transplantation. 1045 40

The two-layer method, which supplies sufficient oxygen to the canine pancreas graft and allows adenotriphosphate synthesis within the graft, resuscitates the ischemically damaged pancreas graft during mild hypothermic (20 degrees C) preservation, but the mechanisms are unknown. The purpose of this study was to determine whether protein synthesis was performed on ischemically damaged pancreas graft during preservation by the two-layer method in a canine autotransplantation model. The pancreas grafts subjected to 90 minutes of warm ischemia were preserved by the two-layer method (perfluorochemical/University of Wisconsin solution) at 20 degrees C for 5 hours. Graft viability was judged from graft survival after autotransplantation. DNA, RNA, and protein synthesis was quantitated by determining incorporation of tritiated thymidine, tritiated uridine, and tritiated leucine, respectively, during preservation. Significant increases in RNA and subsequent protein syntheses were observed during preservation by the two-layer method. In contrast, DNA synthesis did not follow RNA and protein synthesis. We conclude that protein is synthesized in the process of postischemic cellular recovery of the pancreas graft during mild hypothermic preservation by the two-layer method.
Pancreas 2000 May
PMID:Evidence of protein synthesis during resuscitation of ischemically damaged canine pancreas by the two-layer method. 1082 98


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