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

Initial function of the graft is an essential factor for successful liver transplantation. The aim of this study was to evaluate the influence of the nutritional status of the donor on hepatic graft quality at reperfusion. Livers (n = 41) were taken from pigs normally fed or fasted for 24 h or fasted for 24 h and conditioned for 2 hours with a solution containing glucose, fructose and glutamine. The quality of liver grafts was evaluated using an original, blood-free isolated perfusion model, after 8 h cold storage, or after 15 min warm ischemia performed prior to harvesting. The hepatic concentration of glycogen and ATP, measured from in vivo biopsies, was decreased in fasted animals (P less than 0.05 vs fed) and restored by nutritional conditioning (P less than 0.05 vs fasted). At the time of reperfusion following 8 h cold ischemia, the liberation of aminotransferases and lactate dehydrogenase was elevated in livers coming from fasted animals (P less than 0.05 vs fed) and restored to fed levels after nutritional conditioning (P less than 0.01 vs fasted). After 15 min of warm ischemia, the bile secretion during the reperfusion period was decreased in the 24 h fasted livers (P less than 0.01 vs fed) and reestablished after nutritional conditioning (P less than 0.01 vs fasted). Perfusion of the donor liver, in the 2 h preceding harvest, with a solution of glucose plus neoglucogenic precursors enhances the quality of the liver graft at the time of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of nutritional status of the donor on the quality of hepatic graft. Value of restoration of glycogenic reserves of the donor]. 152 97

Several lines of evidence indicate a role for elevated intracellular Ca2+ in mechanisms of cell killing induced by a wide variety of agents. Cardiac myocytes are susceptible to killing under various conditions, including ischemia and exposure to monensin. In order to delineate the Ca(2+)-dependent cell killing mechanism(s) to which cardiac myocytes are susceptible, we have investigated the mechanism by which they are killed by Ca2+ plus the divalent cation ionophore A23187. Evidence has been obtained for two Ca(2+)-mediated injury steps followed by a Na(+)-mediated step leading to cell death detected as membrane permeabilization to trypan blue dye. The first Ca(2+)-mediated step requires the presence of A23187 and low extracellular Ca2+ concentrations (1-100 microM) and is inhibited by Mn2+ and Ni2+ ions. The second Ca(2+)-dependent step requires extracellular Ca2+ concentrations in approximately the physiological range (greater than 1 mM), is not dependent on ionophore, and is not inhibited by Mn2+. Arachidonic acid release occurs during both Ca(2+)-mediated steps, but mostly during the second step. The second injury step is characterized by visible cell swelling and release of lactate dehydrogenase enzyme activity. The Na(+)-dependent step requires extracellular Na+ equal to or greater than half the physiological concentration (i.e., greater than or equal to 75 mM). Li+, which has a smaller ionic radius than Na+, can partially substitute for its in the Na(+)-dependent step, whereas K+, Cs+, Rb+, and NH4+ (which have larger ionic radii) cannot.
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PMID:Sodium- and calcium-dependent steps in the mechanism of neonatal rat cardiac myocyte killing by ionophores. II. The calcium-carrying ionophore, A23187. 152 52

alpha B crystallin, a heat-shock-like protein, is a major component of the soluble protein fraction of the heart and is thought to play a protective role in stress situations. During an ischemic episode, the cytosol of cardiomyocytes acidifies, thus causing the aggregation of the protein with cytoskeletal elements. After homogenization of the tissue, alpha B crystallin can then be recovered with the insoluble cell components. This study investigated the change of the solubility properties of crystallin in the ischemic heart. The distribution of crystallin in the soluble and insoluble cellular fractions was determined by centrifugation of heart homogenates and immunoblot analysis with anti-alpha B crystallin antibodies. The proportion of aggregated alpha B-crystallin increased in hearts reperfused after total normothermic ischemia of increasing severity. alpha B crystallin aggregation was proportional to the amount of lactate dehydrogenase activity released by the hearts and was inversely correlated to the ability of the hearts to recover contractile activity after the ischemic episode. This study shows that the amount of aggregated crystallin can be used as a new marker for the ischemic damage of the heart. Biopsies of a few milligrams are sufficient for the analysis.
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PMID:Determination of alpha B crystallin aggregation: a new alternative method to assess ischemic damage of the heart. 156 52

Using the isolated perfused rat liver, we investigated the relationship of glutathione (GSH) with reactive oxygen species (ROS) generation and liver cell damage during ischemia/reperfusion in normal and GSH-depleted conditions. Lucigenin-enhanced chemiluminescence was used as a sensitive index of tissue ROS generation. After 30 minutes of equilibration, livers were subjected to global ischemia for various times (60 or 90 minutes) and then reperfused for another 120 minutes. Intracellular ROS levels increased sharply at the onset of reperfusion and then declined slowly. After 30 to 60 minutes of reperfusion, ROS levels started to increase progressively in a linear fashion. However, sinusoidal glutathione disulfide release did not increase during reperfusion in the same livers, suggesting that intracellular ROS generation is too low to cause a significant increase in GSH oxidation. Pretreatment with phorone (300 mg/kg intrapentoneally [ip]), which reduced hepatic GSH by 90%, did not cause any difference in intracellular ROS generation compared with the control livers. There were also no significant differences in lactate dehydrogenase and thiobarbituric acid reactive substances (TBARS) release between the control and phorone-treated livers during reperfusion after various times of ischemia. These data indicate that ROS generation in the normal isolated perfused liver during ischemia/reperfusion is extremely low and intracellular GSH does not serve as a major intracellular defense system against such a low oxidative stress.
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PMID:Glutathione and ischemia-reperfusion injury in the perfused rat liver. 157 30

To further define the relationship between oxygen dependence of lung injury during ischemia and ischemia-reperfusion, we used the isolated, perfused, and ventilated rat lung model, so that oxygenation and perfusion could be separated. During ischemia, lungs were ventilated with various oxygen concentrations and then ventilated with 95% oxygen during the 60-min reperfusion period. Other lungs were ventilated with 0% oxygen (nitrogen) during ischemia, and the reperfusion phase oxygen concentration was varied. Tissue and perfusate lipid peroxidation products (thiobarbituric acid-reactive substances and conjugated dienes), dry-to-wet weight ratio, and lactate dehydrogenase were measured as indexes of lung damage. In addition, electron microscopy of some lungs was performed. Results demonstrate an oxygen dependence of lipid peroxidation in both the ischemic and reperfusion phases, but lipid peroxidation is severalfold greater in the reperfusion than in the ischemic phase. Products of lipid peroxidation closely correlate with indexes of lung injury (dry-to-wet weight ratio, lactate dehydrogenase, and electron microscopy).
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PMID:Oxygen-dependent reperfusion injury in the isolated rat lung. 159 38

Phospholipase D (PLD) activity was found to be present in the membrane fraction of rat myocardial cells by in vitro assays (36.7 +/- 4.1 nmol/mg protein per h against 1-palmitoyl-2-arachidonoyl- phosphatidylcholine) and demonstrated in intact cells by the specific transphosphatidylation reaction (in the presence of 0.02% ethanol) quantitated using n-[1-14C]butanol (201.16 +/- 7.1 pmol/min per g dry weight in the whole heart). Both methods showed a significant increase in PLD activity (by 62 and 44%, respectively) in hearts subjected to reversible (30 min) global normothermic ischemia followed by reperfusion (30 min). In hearts prelabeled with [1-14C]arachidonic acid, ischemia/reperfusion induced a significant increase in the amount of radiolabel incorporated into phosphatidic acid (PtdOH) (by 49.6%) and diacylglycerol (DG) (by 259%). DG kinase inhibition by 100 microM dioctanoylethylene glycol did not affect the ischemia/reperfusion DG and PtdOH levels while PtdOH phosphohydrolase inhibition with 40 microM propranolol produced a further increase in PtdOH (to 2.36-fold the baseline level) and a reduction in DG (to only 145% over the baseline levels). Put together, all these results suggest an activation of PLD during myocardial ischemia/reperfusion generating intracellular PtdOH, part of which is converted by PtdOH phosphohydrolase to DG. We further investigated the possible pathophysiological significance of the observed PLD activation. Stimulation of PLD with sodium oleate (20 microM) induced a significant improvement of functional recovery of ischemic hearts during reperfusion (as monitored by coronary flow and left intraventricular pressure measurements) and an attenuation of cellular injury as expressed by lactate dehydrogenase and creatine kinase release in the coronary effluent during reperfusion. These results suggest a PLD-mediated signaling in the ischemic heart which may benefit functional recovery during reperfusion.
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PMID:Phospholipase D signaling in ischemic heart. 161 Sep 13

Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.
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PMID:Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats. 163 55

Experimental evidence is presented that directly links ischemia/reperfusion injury to the formation of oxygen-derived free radicals. 2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO)--a stable nitroxide radical that disproportionates superoxide radicals and oxidizes reduced metal ions required for OH. formation--was tested for its ability to prevent reperfusion damage in the isolated rat heart subjected to regional ischemia. Severe reperfusion arrhythmia--ventricular fibrillation and ventricular tachycardia--were prominent in control hearts, and their duration was significantly reduced by the presence of 0.4 or 1 mM TEMPO. TEMPO also repressed both postischemic release of lactate dehydrogenase and OH. formation. TEMPO slowed the heart rate, but compensatory pacing did not alter the dramatic effect of the nitroxide on reperfusion arrhythmia. TEMPO was partially protective when introduced at the end of ischemia but had no effect when added 1 min into reperfusion. It was concluded that both reperfusion arrhythmia and cell damage were directly related to oxidative damage incurred during the critical first minute of reperfusion. TEMPO strongly protected against reperfusion injury by preventing the formation of OH. and not by decreasing heart rate or by direct suppression of arrhythmia.
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PMID:Cardiac reperfusion damage prevented by a nitroxide free radical. 164 12

The pathophysiology of cold injury was examined by cooling a hind leg of an anesthetized New Zealand white rabbit. A flow probe and a thermocouple were placed in the leg to be cooled to monitor the blood flow and tissue temperature. After baseline measurements, the leg was cooled with a freezing mixture up to 0 degrees C, which was followed by rewarming. The other leg served as control. In the experimental group, liposome-bound superoxide dismutase and catalase were infused through the femoral vein 15 minutes prior to putting the freezing mixture on the leg. Salicylic acid was injected through the femoral vein at the end of some experiments to assay hydroxy radical (OH). Our results demonstrated reduction of local blood flow in cold-exposed leg, indicating development of ischemia. Creatine kinase and lactage dehydrogenase were increased during rewarming in conjunction with hydroxyl radical formation, phospholipid breakdown, and lipid peroxidation. Treatment with superoxide dismutase and catalase reduced OH formation, prevented phospholipid degradation, and decreased creatine kinase, lactate dehydrogenase, and malonaldehyde formation. These results indicate that rewarming of cooled tissue is associated with "rewarming injury" similar to "reperfusion injury", and that oxygen-derived free radicals play a significant role in the pathophysiology of such injury.
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PMID:Reduction of cold injury by superoxide dismutase and catalase. 164 16

1. Nilvadipine (FK 235, FR 34235) suppressed ischemia (20 min)-reflow (20 min)-induced paw edema of mice (ED30:0.4 mg/kg i.v. and 2 mg/kg p.o.). Other calcium entry blockers of dihydropyridine-type also suppressed the edema, but 30-fold higher doses were required. 2. Oral dosing of nilvadipine suppressed carrageenan-induced paw edema (ED30:15 mg/kg in rats and 20 mg/kg in mice) at a potency corresponding to that of an anti-inflammatory drug, ibuprofen. Nifedipine, nicardipine and nimodipine resulted in a suppression of 30% only with 100 mg/kg oral dosing in rats. Nitrendipine, diltiazem and verapamil were without effect. 3. Nilvadipine inhibited superoxide radical (O-2production from xanthine oxidase (XOD) both with lactate dehydrogenase + NADH method and cytochrome c method (IC50:90 and 100 micrograms/ml, respectively). Nifedipine and nicardipine showed some inhibition, but the other calcium entry blockers failed to inhibit significantly even at 320 micrograms/ml. As uric acid formation was not reduced by the tested drugs, the inhibitory action might be due to their O-2scavenging effects. 4. Superoxide production of neutrophils from casein-induced peritoneal fluid in rats was most strongly inhibited by nilvadipine when the cells were stimulated by a calcium ionophore, A23187 (IC50:4 micrograms/ml). Inhibition by this drug when stimulated by f-methonyl-leucyl-phenylalanine and phorbol myristate acetate was less effective (IC50:20 and 30 micrograms/ml, respectively). Nifedipine and nicardipine inhibited neutrophil O-2production at higher concentrations (30-200 micrograms/ml) with all stimulants. Inhibitory actions by other drugs were weak. 5. Triggering of atherosclerosis depends largely on the oxidative stress on blood vessels after recently established concept.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition by nilvadipine of ischemic and carrageenan paw edema as well as of superoxide radical production from neutrophils and xanthine oxidase. 165 7


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