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

We examined the effects of two degrees of hypothermia on hepatic oxygen delivery and uptake, hepatic lactate uptake as a marker of hepatic function, and the effect of hypothermia on ischemia-reperfusion injury in the liver in miniature pigs (n = 18, 21-30 kg body wt). Hepatic arterial and portal venous blood flows were measured while hepatic oxygen delivery was progressively decreased without venous congestion in the preportal area. With decreases in hepatic blood and oxygen supply, oxygen extraction gradually increased from 50 to 90% in the normothermic group and from 25 to 70 and 84% in the hypothermic (30. and 34 degrees C, respectively) groups. The values of critical hepatic oxygen delivery were between 7.3 and 11.9 ml O2.min-1.100 g-1 without significant differences among the groups. During reperfusion after ischemic insult, hepatic oxygen uptake returned to base-line values in both hypothermic groups but remained substantially below base-line values in normothermic groups of animals. Hepatic enzyme concentrations (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and alcohol dehydrogenase) were substantially increased (up to 30-fold) in normothermic animals, but the concentrations did not increase in either of the hypothermic groups. These results demonstrated that hypothermia per se does not affect hepatic oxygen delivery but decreases hepatic oxygen demand and uptake, provides an effective protection from hepatic oxygen deprivation, and lessens reperfusion injury.
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PMID:Hypothermia, hepatic oxygen supply-demand, and ischemia-reperfusion injury in pigs. 236 Jun 37

The changes in the contents of the main tricarboxylic acid cycle intermediates and related amino acids under total ischemia and subsequent reperfusion of isolated guinea pig heart were studied. The decrease in ATP and phosphocreatine during 30 min ischemia was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate. The succinate production was commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of bulk amount of lactate, alanine and succinate into the myocardial effluent was observed during an early phase of the reperfusion using 1H NMR. In contrast to these metabolites, malate release was not observed in the reperfusion. By the 30th min of the reperfusion the decrease in lactate, alanine, malate and succinate tissue contents to the preischemic values was accompanied by the recovery of ATP and phosphocreatine. The results suggest that the formation and the release of succinate and alanine from the heart, complementary to that of lactate, reflect profound disturbances in energy metabolism.
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PMID:Metabolism of the tricarboxylic acid cycle intermediates and related amino acids in ischemic guinea pig heart. 289 8

The effects of total ischemia and subsequent reperfusion on the formation of anaerobic metabolism products and their release into myocardial effluent were studied in isolated guinea pig hearts. During 30-min ischemia myocardial ATP and phosphocreatine decreased to 34 and 15% of the initial levels, respectively; this was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate; the succinate production being commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of lactate, alanine, succinate, creatine and pyruvate trace amounts into the myocardial effluent was observed during an early phase of the reperfusion using 1H-NMR. The rates of metabolite release reduced as follows: lactate much greater than alanine greater than succinate greater than creatine. By the 30th min of the reperfusion the decrease in these metabolites tissue contents was accompanied by the recovery of ATP and phosphocreatine levels up to 65 and 90% of the initial ones, respectively. The data obtained demonstrate that the formation and the release of succinate, alanine and creatine from the heart as well as of lactate may indicate profound disturbances in energy metabolism.
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PMID:An assessment of anaerobic metabolism during ischemia and reperfusion in isolated guinea pig heart. 337 59

The effect of ischemia on the formation of products of anaerobic metabolism and their release into the cardiac effluent in isolated perfused guinea pig hearts was studied. During 30 min normothermal ischemia, the myocardial ATP and phosphocreatine levels decreased to 34% and 15% of the initial values, respectively. The net alanine formation in ischemia was approximately a stoichiometric glutamate decrease; the increase in the tissue malate content corresponded to the aspartate----oxaloacetate----malate anaplerotic flux, the succinate production being commensurable to alpha-ketoglutaric acid formation in the alanine aminotransferase reaction. Using 1H-NMR, it was shown that the release of trace amounts of lactate, alanine, succinate, creatine and pyruvate into cardiac effluents occurred during the first 5 minutes of reperfusion. The rate of metabolite release decreased in the following order: lactate much greater than alanine greater than succinate greater than creatine. By the 30th minute of reperfusion, the decrease in the tissue levels of these metabolites to preischemic values was accompanied by the recovery of ATP and phosphocreatine to 65% and 90% of the initial levels, respectively. The data obtained suggest that the formation and release of alanine, creatine or succinate as well as lactate from ischemic myocardium may testify to significant disturbances in energy metabolism of the myocardium.
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PMID:[Formation of products of anaerobic metabolism in the ischemic myocardium]. 337 64

The biochemical characterization of experimental acute pancreatitis was performed by determination of the secretory enzymes lipase and alpha-amylase, of the cytoplasmic ALAT (alanine aminotransferase), of total protein and calcium concentration in serum of rats. The moderate and protracted course of the pathological process in the small animal model presented allowed to study the initial phase from 1-24 h. In the first 4-8 h most massive enzyme release into the intravasal space was observed. The level of enzyme activities was correlating with the severity of assault. One noxa alone (ischemia or juice edema) resulted in a moderate enzyme release (lipase : 2-2.5 fold of control). The action of both noxae caused a drastical increase in enzyme activities in the initial phase lipase : 8-20 fold, ALAT: 7 fold, alpha-Amylase: 2.5 fold). 24 h postoperatively the serum enzyme activities were at distinct pathological level. At this time acute pancreatitis provoked already a decreased serum protein content. A hypocalcemia was not observed.
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PMID:Contribution of pancreatic edema and short-term ischemia to experimental acute pancreatitis in the rat. II. Behaviour of serum parameters. 349 93

We examined the polyamine metabolism in liver transplanted after cold ischemia and effects of putrescine administration on liver injury, liver regeneration, and survival rate after orthotopic liver transplantation in the rat. Male Wistar rats were used as donors and recipients. Grafts were stored in Euro-Collins solution for 6 h at 4 degrees C. Orthotopic liver transplantation was performed by the three cuff technique. The activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase elevated and peaked 4 h after liver transplantation. Hepatic ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities were also elevated and peaked 8 h after the operation. In agreement with the increases in ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities, the putrescine content increased and spermidine content decreased in the transplanted liver. Putrescine administrated intraperitoneally improved the survival rate, decreased serum transaminase level and increased the [3H]thymidine incorporation into the liver DNA. These findings suggest that both biosynthetic and biodegradative pathways are stimulated in liver transplantation, resulting in the increase in the formation of putrescine from ornithine and from spermidine, and that putrescine administration improve the survival rate by protecting the damaged graft after cold ischemia and reperfusion and by stimulating liver regeneration.
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PMID:Polyamine metabolism in the rat liver after orthotopic liver transplantation. 749 79

Amlodipine, a long acting calcium antagonist, was used to reduce the adverse effects of ischemic/reperfusion injury studied in isolated perfused rat livers. Amlodipine (10 mumol/L) was added to University of Wisconsin (UW) solution in which the liver was stored for 24 hr at 4 degrees C and incorporated in the saline flush used to displace the UW solution before 20 min of warm ischemia (at 37 degrees C) and reperfusion. Initial median blood flow at 15 min was significantly higher after amlodipine treatment (2.78 vs. 1.41 ml/min/g of liver without amlodipine treatment, P = 0.013) as was the area under the curve of blood flow for the entire 3-hr perfusion (472 vs. 316 ml/g of liver, P = 0.003). Amlodipine treatment induced corresponding increases in oxygen delivery (1302 vs. 896 mumol of O2/g of liver over 3 hr of perfusion, P = 0.003) and oxygen consumption (279 vs. 242 mumol of O2/g of liver over 3 hr, P = 0.06). Initial bile flow at 15 min was increased 4-fold by amlodipine treatment (17.27 vs. 4.59 mg/hr/g of liver for sequential cold and warm ischemia, P = 0.013), and the median area under the curve of bile flow for the entire perfusion increased to 92.2 vs. 53.9 mg/g of liver (P = 0.0006). Amlodipine treatment also reduced glucose release into the perfusate (116 vs. 149 mmol/L/g of liver min over 3 hr, P = 0.03) and prevented hepatocyte injury by reducing alanine aminotransferase release both initially (0.43 vs. 0.96 IU/L/g of liver, P = 0.055) and overall (343 vs. 797 IU/L/g of liver min, P = 0.048). When amlodipine was added only to the UW solution, blood flow increased by 66% initially (P = 0.02) and 32% overall (P = 0.013), but there was no corresponding improvement in hepatic function. Amlodipine may reduce hepatic ischemic/reperfusion injury by cytoprotective effects on parenchymal and non-parenchymal hepatocytes during both preservation and reperfusion leading to an improvement in liver microcirculation and an inhibition of the release of toxic mediators.
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PMID:Amlodipine improves hepatic hemodynamic and metabolic function in the isolated perfused rat liver after sequential cold and warm ischemia. 762 39

The effects of warm ischemia were investigated in obese Zucker rats with severe hepatic steatosis in order to develop a nontransplant fatty liver ischemia model. Obese (Ob) and lean (Ln) Zucker rats were subjected to in vivo partial hepatic warm ischemia of 45 or 90 min. Injury was assessed by serum alanine aminotransferase, animal survival, and liver histology. Liver lipids were quantified in control animals. After 90-min ischemia and 2-hr reperfusion, liver malondialdehyde was measured and neutrophils in 12 microscopic fields were counted after esterase staining. After 45 and 90 min of ischemia, Ob animals had significantly higher alanine aminotransferase at 1-hr and 24-hr reperfusion, compared with Ln animals (P < 0.01). After 90 min of ischemia, none of the Ln and 8/9 Ob animals died within 48 hr (P < 0.01). Histologically, Ob animals had more hepatocyte necrosis than did Ln animals. Hepatic neutral and phospholipid content (mg/g) in Ob versus Ln animals was 45.2 +/- 2.6 versus 8.2 +/- 0.7 (P < 0.01) and 36.2 +/- 1.9 versus 27 +/- 2.2 (P < 0.05), respectively. After reperfusion, liver malondialdehyde content increased significantly in Ob animals (8.5 +/- 0.4 vs. 12.3 +/- 0.8 pM/mg protein; P < 0.05), but not in Ln animals. Neutrophils, scant in control livers, increased significantly (P < 0.01) after ischemia/RP, but it increased to a similar degree in Ob and Ln animals. Obese Zucker rats with hepatic steatosis are more susceptible to warm ischemia/reperfusion injury than lean animals, and lipid peroxidation may be an important contributory mechanism. Further studies in this model might help to investigate the human problem.
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PMID:Studies of hepatic warm ischemia in the obese Zucker rat. 770 52

This study aimed at analyzing the involvement of platelet activating factor (PAF) in ischemia/reperfusion injury (I/R) of the liver. Male Wistar rats under pentobarbital anesthesia were subjected to 60 min of normothermic ischemia of the left and median liver lobes, followed by 30 min of reperfusion in vivo. Blood pressure and body temperature were controlled throughout the experiment. Preischemic injection of a specific PAF antagonist (BN52021, 5 mg/kg body mass) resulted in significant reduction of postischemic enzyme loss into the serum from the vascular endothelium (purine nucleoside phosphorylase: 56.9 +/- 11.4 vs 86.6 +/- 20.4 U/l**) and the hepatic parenchyme (alanine aminotransferase: 176 +/- 60 vs 519 +/- 180 U/l***), accompanied by a significant increase of hepatic bile production (1.28 +/- .32 vs 0.80 +/- 0.16 microliter/g/min*) and tissue levels of ATP (6.12 +/- 1.73 vs 4.21 +/- 1.30 mumol/g*). Laser Doppler flowmetry revealed a significant improvement by BN52021 of left lobular erythrocyte flux recovery from 27 +/- 25 to 78 +/- 19% of respective preischemic control values. The data give evidence for an implication of PAF in I/R damage to the vascular endothelium and in impaired parenchymal function of the liver, probably due to altered microvascular reperfusion. Treatment with PAF antagonists should improve results after liver surgery under ischemic conditions. (*;**;***: P < 0.05; 0.01; 0.001).
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PMID:Involvement of platelet activating factor in microcirculatory disturbances after global hepatic ischemia. 774 67

The potential beneficial effect of hepatocellular glutathione against inflammatory liver damage was investigated in a model of endotoxin-enhanced ischemia-reperfusion injury. Animals were subjected to 20 min of hepatic ischemia, followed by 4 hr of reperfusion. The injection of 0.5 mg/kg Salmonella enteritidis endotoxin potentiated liver injury and the postischemic oxidant stress, as indicated by increased plasma levels of glutathione disulfide. Depletion of hepatic glutathione levels by > 90% with phorone and inhibition of glutathione synthesis with buthionine sulfoximine further increased liver injury in this model, as indicated by enhancement of plasma alanine aminotransferase activities from 2,234 +/- 122 U/L to 4,024 +/- 282 U/L. Continuous infusion of a glutathione (GSH) solution in GSH-depleted animals (22 mumol/kg/hr) attenuated reperfusion injury by 55%. In vitro experiments demonstrated the capability of GSH to react rapidly with reactive oxygen species, such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Only H2O2 oxidized GSH quantitatively to its disulfide; HOCl oxidized GSH to higher oxidation states. These data support the hypothesis that the enhanced release of hepatocellular GSH functions as a defense mechanism against reactive oxygen species generated by inflammatory cells during endotoxemia and reperfusion. This internal defense system of the liver may be of general importance in preventing, or at least limiting, liver damage by reactive oxygen generated in particular by Kupffer cells during their physiological function to remove gut-derived endotoxin and bacteria.
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PMID:Beneficial effects of extracellular glutathione against endotoxin-induced liver injury during ischemia and reperfusion. 783 22


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