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)

A model of transient acute hepatic failure has been developed in the pig. Three days after a functional end-to-side portacaval shunt was introduced, 15 ambulant animals underwent total liver ischemia for 4 to 6 h by the closure of a mechanical clamp surrounding the hepatic artery. Four of the eight animals subjected to 4 hr of ischemia survived. All but one of the animals undergoing 6 hr of hepatic ischemia developed grade 4 encephalopathy after 24 to 30 hr and died within 50 hr. Quantitative estimation of liver cell necrosis revealed less than 40% necrosis in the survivors, and approximately 62% (range 49-75%) in animals who died of hepatic coma. As far as the putative toxins are concerned, significant differences were found between animals undergoing 4 and those undergoing 6 hr of ischemia, especially in the plasma ammonia levels and the plasma ratios for tyrosine and phenylalanine. Plasma arginine levels had fallen to zero in both groups at 24 hr and only rose to preischemic values in animals who survived. This large animal model fulfills the accepted criteria of potential reversibility, reproducibility, and death due to hepatic failure.
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PMID:A reproducible model of acute hepatic failure by transient ischemia in the pig. 380 58

Brain ischemia was induced for 10 or 30 min by clamping the common carotid arteries in rabbits whose vertebral arteries had previously been electrocauterized. EEG and tissue content of high energy phosphates were used to verify the ischemic state and to evaluate the degree of postischemic recovery. Extracellular levels and total contents of amino acids were followed in the hippocampus during ischemia and 4 h of recirculation. At the end of a 30-min ischemic period, GABA had increased 250 times, glutamate 160 times, and aspartate and taurine 30 times in the extracellular phase. The levels returned to normal within 30 min of reflow. A delayed increase of extracellular phosphoethanolamine and ethanolamine peaked after 1-2 h of reflow. Ten minutes of ischemia elicited considerably smaller but similar effects. With respect to total amino acids in the hippocampus, glutamate and aspartate decreased to 30-50% of control while GABA appeared unaffected after 4 h of reflow. Alanine, valine, phenylalanine, leucine, and isoleucine increased severalfold. The importance of toxic extracellular levels of excitatory amino acids, as well as of high extracellular levels of inhibitory amino acids, are considered in relation to the pathophysiology of neuronal cell loss during cerebral ischemia.
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PMID:Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments. 403 Sep 18

The levels of amino acids in 6 regions of the brain (cortex, hippocampus, striatum, diencephalon, stem and cerebellum) were determined during an ischemic insult of 30 min and after recovery periods of up to 10 h. The results were analyzed in two groups: putative neurotransmitters (GABA, aspartate, glutamate, taurine, glycine and alanine) and non-neurotransmitters. In the neurotransmitter group, it was found that at the end of 30 min ischemia the levels of aspartate and glutamate slightly decreased whereas those of GABA and alanine rose substantially. The amounts of glycine and taurine remained unchanged. In 30 min after the ischemic insult, there were much larger decreases in aspartate and glutamate and increases in GABA and alanine with no change in glycine and taurine. At 2 h recovery the levels of the neurotransmitter amino acids had almost returned to control values and were fully recovered by 10 h after ischemia. It is postulated that glutamate and aspartate are released during ischemia into the extracellular space and subsequently 'washed-out' into the blood during the reperfusion. Release of GABA, if it occurs, is however, compensated by increase in its synthesis and decrease in its degradation under anaerobic conditions, both of which contribute to the rise in its steady-state level. In the non-transmitter category, increases were seen in amino acids present normally in very small concentrations; tyrosine, lysine, leucine and 3 hydrophobic amino acids: valine, methionine and phenylalanine, which were most pronounced at 2 h after ischemia. It is suggested that the rise in the levels of these molecules is the consequence of stimulation of protein breakdown caused by activation of intracellular proteases by calcium and H+ during the ischemic episode. Regional variations in the patterns of changes were small although in the ischemic models used the brainstem seemed to be least affected.
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PMID:Neurotransmitter amino acids in the CNS. I. Regional changes in amino acid levels in rat brain during ischemia and reperfusion. 614 83

Although acute perfusion of guinea pig hearts with ethanol does not affect cardiac protein synthesis, the latter is inhibited after prolonged ingestion of ethanol when tested in an in vitro system with the working right ventricle. This study reports on the added stress of ischemia on such hearts. Hearts were removed from maturing guinea pigs after 13-16 weeks of ingesting 10% ethanol and were perfused in vitro under conditions of relative ischemia (one-sixth of normal coronary flow) with maintenance of right ventricular load and outflow resistance identical to normal pre-ischemic levels. With this degree of ischemia, there was a 4-6 fold increase in lactate production, an 80% drop in ATP, and a 90% decrease in creatine phosphate after 150 min of the ischemia. Incorporation of both labeled lysine and phenylalanine into cardiac protein was also diminished to 35% of control in the left ventricle and 55% of control in the right. This diminution of protein synthesis was the same in hearts from ethanol-drinking and matched control animals. Thus, prior prolonged ingestion of ethanol did not worsen the inhibition of protein synthesis by oxygen deprivation. There were, however, two significant differences in hemodynamic response to the ischemia by the right ventricles of hearts from ethanol-drinking guinea pigs compared to their matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolonged feeding of ethanol to the young growing guinea pig. II. A model to study the effects of severe ischemia on cardiac protein synthesis. 642 90

Hypoxia and anoxia were induced in isolated perfused rat hearts by reduction of perfusate oxygen. Ischemia was produced by restricting coronary flow in hearts working against high resistance. Protein degradation, estimated from release of phenylalanine into the perfusate in the presence of cycloheximide, was inhibited in both anoxic and ischemia as compared to aerobic hearts. The effect of ischemia was greater than that of anoxia. A similar inhibitory effect was observed in energy-poor hearts when insulin was present in the perfusate. Other experiments indicated that the effects of energy depletion were exerted at a step early in the degradative pathway, since peptide products of partial proteolysis did not accumulate. A graded reduction in perfusate oxygen tension (hypoxia) led to a significant inhibition of proteolysis with unaltered tissue levels of nucleotides and creatine phosphate. Protein degradation was inhibited in aerobic and anoxic hearts exposed to increasing extracellular levels of hydrogen ions and lactate, suggesting that reduced proteolysis in hearts that are provided limited oxygen may result from accumulation of metabolites as well as from energy depletion per se.
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PMID:Inhibition of protein degradation in the energy-poor heart. 699 87

Normothermic, temporary, total ischemia of the liver was produced for 60-225 min under transient portal decompression with a by-pass between the mesenteric and the femoral vein. Total amino acids in the liver tended to increase after an ischemic period of more than 120 min without reperfusion as compared with control with increasing trends in most of the individual amino acids. In a group undergoing 120 min of ischemia and 60 min of reperfusion, total amino acids and individual amino acids tended to decrease. Total plasma amino acids significantly increased after ischemia of more than 120 min. Without reperfusion, elevations of almost all amino acids except for branched chain amino acids were found, whereas after reperfusion most of the individual amino acids also increased including branched chain amino acids. Molar ratios of branched chain amino acids to tyrosine and phenylalanine decreased only after more than 120 min ischemia without reperfusion. Volume ratios of organelle disintegration on electron micrographs such as mitochondrial degradation and autophagic vacuoles were moderately increased after 90 min ischemia with a further steep rise after more than 120 min ischemia. The survival rates of the animals after 60, 90 and 120 min ischemia were 35% (6/17), 27% (3/11) and 25% (3/12), respectively. The following conclusions were obtained: 1) Pre-necrosis of the hepatocytes with simultaneous protein degradation started after ischemia for about 2 hr. The survival rates of the animals after 60 and 90 min ischemia were very low despite of mild necrosis of the liver. 2) Most of the amino acids in the liver were washed out into the plasma to cause an abnormal plasma amino acid pattern in the acute state. However, the molar ratio of branched chain amino acids to aromatic group was not reduced, in contrast to the ischemic group without reperfusion.
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PMID:Postischemic liver damage in rats: amino acid analysis and morphometric studies. 714 34

The mechanisms involved in hypertrophy of the left ventricle were studied in Langendorff-perfused rat hearts by measuring the ventricular protein synthesis and its transmural distribution and by differentiating between the effects of changes in mechanical work load, intraventricular and coronary pressures. An increase in the aortic pressure from 7.85 kPa (80 cm of water) to 19.6 kPa (200 cm of water) in beating hearts increased phenylalanine incorporation into left ventricular protein from 1.4 to 2.0 mumol/g protein (p less than 0.02) during a two-hour perfusion. The protein synthesis was transmurally evenly distributed. A similar elevation in the perfusion pressure in potassium arrested hearts caused an increase in phenylalanine incorporation from 1.5 to 1.9 mumol/ (p less than 0.05) when the intraventricular pressure was adjusted to zero, indicating that the increase in aortic (coronary) pressure and not the work load per se was the reason for increased protein synthesis. Elevation of the end-diastolic pressure from zero to approximately 2 kPa in beating hearts at an aortic pressure of 7.85 kPa, or from 7.85 kPa to 17.3 kPa in K+-arrested hearts, at an aortic pressure of 19.6 kPa caused a significant reduction in subendocardial protein synthesis, whereas subepicardial phenylalanine incorporation was at most only slightly affected. The energetic parameters, oxygen consumption, output of vasoactive purine compounds and distribution of coronary flow indicate that the increase in protein synthesis via the elevation in aortic pressure was not due to the abolition of partial anoxia, whereas the same parameters indicate that the transmural gradient in protein synthesis observed under certain conditions was due to subendocardial ischemia when the intraventricular pressure approached the aortic pressure in arrested hearts, which are evidently of restricted use for extended periods without special measures to limit the build-up of intraventricular pressure.
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PMID:Protein synthesis in the isolated perfused rat heart. Effects of mechanical work load, diastolic ventricular pressure and coronary pressure on amino acid incorporation and its transmural distribution into left ventricular protein. 723 77

Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB2) is the integrin receptor on PMNs critical for adhesion-dependent oxidative burst. The purpose of this study was to investigate the mechanistic role of CD11b in the process of gut I/R-induced lung injury. Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery (SMA) occlusion with and without CD11b monoclonal antibody treatment (IB6) (1 mg/kg, i.v.), before SMA clamping. At 2-hour reperfusion, PMN presence in tissue was quantitated by myeloperoxidase activity and circulating PMN priming determined by the difference in superoxide production with and without N-formyl-methionyl-leucyl-phenylalanine, whereas lung leak was assessed by 125I-albumin lung/blood ratio. In sum, CD11b blockade prevented gut I/R-induced lung leak, but did not attenuate gut I/R-induced PMN priming or tissue PMN accumulation. In conclusion, gut I/R promotes PMN priming and PMN adhesion in both local and distant beds via receptors other than CD11b, but this B2 integrin receptor is critical for PMN-mediated endothelial injury.
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PMID:CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion. 763 6

We evaluated the effect of 4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride) on superoxide production by human neutrophils using an MCLA-dependent chemiluminescence assay. Bifemelane hydrochloride dose-dependently inhibited superoxide production by neutrophils stimulated with phorbol myristate acetate, opsonized zymosan, or N-formyl-methionyl-leucyl-phenylalanine, while it had no effect on superoxide production by a hypoxanthine-xanthine oxidase system. These results indicate that bifemelane hydrochloride does not have a scavenging effect, but has an inhibitory effect on superoxide generation by neutrophils. Although this drug is commonly used for treating chronic cerebral infarction, it may also have a protective effect on acute ischemia/reperfusion injury.
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PMID:Inhibitory effect of bifemelane on superoxide generation by activated neutrophils measured using a simple chemiluminescence method. 783 51

Granulocyte adhesion to ischemic tissue, mediated in large part by beta 2 integrin receptors, is important in the pathophysiology of reperfusion injury. Acadesine, a drug that modulates adenosine levels in ischemic tissue, has been shown to reduce reperfusion injury in animal models of ischemia. The purpose of this study was to measure changes in granulocyte CD11b/CD18 in an in vitro assay and in an in vivo trial of acadesine administered during cardiopulmonary bypass to determine whether this agent might modulate up-regulation of this adhesion receptor. In vitro, whole blood was incubated with acadesine or control diluent, stimulated with N-formyl-methionyl-leucyl-phenylalanine, and granulocyte CD11b measured. Acadesine significantly (p < 0.01) inhibited N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61%. In similar experiments, adenosine also inhibited N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation (p < 0.01). In vivo, 34 patients at our institution participating in a multicenter trial of acadesine during cardiopulmonary bypass were randomized to placebo, low-dose, or high-dose acadesine infusion perioperatively. Combining low- and high-dose treatment groups, there was significant (p = 0.05) inhibition of granulocyte CD11b up-regulation in patients receiving acadesine; granulocyte CD11b expression in the acadesine group peaked at 2.8 times baseline versus 4.3 for placebo. By contrast, monocyte CD11b up-regulation (peaking after cardiopulmonary bypass at 3 times baseline) was not affected by acadesine. Acadesine and adenosine inhibit up-regulation of granulocyte CD11b in vitro, and acadesine is capable of a similar inhibition during in vivo cardiopulmonary bypass. This inhibition may contribute to the ability of these agents to decrease in vivo reperfusion injury.
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PMID:Acadesine inhibits neutrophil CD11b up-regulation in vitro and during in vivo cardiopulmonary bypass. 787 5


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