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)

During operation, biopsies from the gastrocnemius muscle and, in some cases, from the sartorius muscle were taken from 32 patients with peripheral arterial occlusive disease and from 5 subjects with normal peripheral circulation. In patients with inadequate circulation only during exercise, when compared with the control group, increased activities of enzymes involved in oxidative metabolism (malate dehydrogenase, nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase, cytochrome C oxidase, creatine kinase), in amino acid metabolism (asparate aminotransferase, alanine aminotransferase), and in anaerobic glycoysis (lactate dehydrogenase) were found. In patients with circulatory disturbances that manifested themselves already at rest, enzyme activities were, with the exception of LDH, lower than those of patients with exclusively exercise-related insufficiency. By means of intraindividual comparisons with the corresponding enzyme activities in the sartorius muscle, the author was able to show that the changes found were not simply the result of differences in training conditions. The diminished concentrations of energy-rich phosphate are an expression of the anaerobic metabolic state in patients with inadequate circulation at rest. It is concluded that chronic ischemia of muscle leads to changes in the energy metabolism of the cell. In the presence of more nearly adequate circulation at rest, the portion of oxidative potential of the total energy metabolism increases. In contrast, if there is an inadequate circulation at rest, the mainly anaerobic glycolysis becomes quantitatively predominant.
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PMID:Investigations on the biochemical characteristics of chronically underperfused muscle. 201 45

We determined if the cardioprotective effects of the potassium channel opener cromakalim are stereoselective and if it can preserve adenine nucleotides in ischemic myocardium. We subjected isolated isovolumically beating rat hearts to 25 min of global ischemia and reperfusion with and without pretreatment by cromakalim or its enantiomers. All of these compounds significantly increased preischemic coronary flow with the (3S,4R)-(-)-enantiomer being more potent (EC25 = 0.52 microM) compared to cromakalim (EC25 = 1.04 microM) and the (3R,4S)-(+)-enantiomer (EC25 greater than 100 microM). The (-)-enantiomer was also significantly more potent in reducing ischemic/reperfusion damage compared to cromakalim and its (+)-enantiomer. Reperfusion contractile function was improved significantly and lactate dehydrogenase release was reduced by these compounds. Time to contracture was also increased significantly by the (-)-enantiomer (EC25 = 2.27 microM), cromakalim (EC25 = 4.89 microM) and the (+)-enantiomer (EC25 greater than 100 microM). We determined if cromakalim, in a concentration which does not depress cardiac function (10 microM), can preserve high energy phosphates during ischemia in isolated rat hearts. Cromakalim significantly preserved ATP at 15 to 25 min of ischemia. Adenylate energy charge was also significantly improved by cromakalim at 20 to 25 min into an ischemic episode. Thus, the cardioprotective effects of cromakalim are stereoselective and may be due partly to preservation of myocardial energy reserves. It is significant that cromakalim can preserve adenine nucleotides despite its lack of negative inotropic effects.
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PMID:Cardioprotective effects of the potassium channel opener cromakalim: stereoselectivity and effects on myocardial adenine nucleotides. 201 83

One of the methods of donor heart protection against ischemia is a substantial lowering of temperature of the heart perfused with cardioplegic solution (CS). The achieved conservation of energetically rich compounds, however, does not guarantee the full restoration of heart function during reperfusion. Another possibility for heart preservation is repeated application of CS at 20 degrees C. This variant was tested in our experiments on isolated rat hearts perfused under constant pressure with the Krebs-Henseleit solution according to Langendorff. During global ischemia (180 min at 20 degrees C) we applied the St. Thomas Hospital CS lx or 4 x at 60 min intervals. During the ischemia, glycogen, ATP, lactate, Na+, K+ were assessed in the heart. The heart injury was monitored as the release of lactate dehydrogenase (LD) during the 60 min reperfusion. Repeated CS perfusion of the heart during ischemia lowers the contents of lactate and maintains ATP and glycogen content at elevated levels throughout ischemia. The improved condition of the heart after repeated CS application demonstrated as prevention of the gain of Na+ in the cells at the end of ischemia as well as after reperfusion. This was associated with reduced intracellular potassium depletion and LD release into the perfusate.
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PMID:A method for slowing down depletion of myocardial energy reserves of the donor heart before transplantation. 202 56

The loss of protection by human recombinant (hr) Cu.Zn-superoxide dismutase (SOD) at higher doses reported previously may have been due to the weak peroxidase activity of this enzyme. To test this possibility we studied the dose-response relationship of hrMn-SOD, which lacks peroxidase activity. Isolated, buffer perfused rabbit hearts were subjected to 1 h of global ischemia followed by 1 h of reperfusion, and the percent recovery of developed tension (relative to preischemic) was measured via a left ventricular balloon connected through a pressure transducer to a polygraph recorder. The coronary effluent was assayed for lactate dehydrogenase (LDH) release. While hrMn-SOD almost completely protected against loss of function and LDH release at 2 and 5 mg/L (p less than 0.01), it exacerbated the damage at 50 mg/L concentration (p less than 0.05 against controls), thus giving an even sharper bell-shaped curve than seen with the hrCu,Zn-SOD. Therefore we conclude that, first, while the hrMn-SOD protects the reperfused heart at lower doses, it may exacerbate the damage at higher doses. Second, that the lack of protection seen at higher doses of hr-Cu,Zn-SOD is unlikely to be due only to its peroxidase activity.
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PMID:The cardioprotective effect of Mn-superoxide dismutase is lost at high doses in the postischemic isolated rabbit heart. 207 27

Apart from pharmacological interventions, four methods can be used to induce myocardial damage in the isolated, perfused heart. These are (i) total global ischemia, where perfusion is stopped completely; (ii) partial ischemia where perfusion is restricted; (iii) regional ischemia, produced by occlusion of the coronary circulation, and (v) hypoxia where the oxygenated buffer is replaced with a buffer bubbled with nitrogen. Using rat hearts, coronary artery occlusion was found to have potential as a screening device for antiischemic compounds. In these studies 45Ca uptake and enzyme release were found to increase with ligation time. The inclusion of the Ca2+ antagonist verapamil (0.01 to 1 microM) resulted in a concentration-dependent inhibition of 45Ca uptake (IC50 = 68 nM); however the proportion of tissue damaged remained unchanged. Similar findings were obtained in the presence of the dihydropyridine Ca2+ antagonist nicardipine (0.1 or 1 microM). Measurement of enzyme release during the reperfusion period confirmed significant correlations between levels of either lactate dehydrogenase (LDH) or creatine kinase (CK) and 45Ca uptake. Studies involving LDH show that cation uptake precedes enzyme release (r = 0.93; p = less than 0.001).
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PMID:Determination of the extent of ischemic damage and the effect of the calcium antagonist, verapamil following coronary artery ligation in the rat. 208 46

Because the intestinal mucosa is most sensitive to ischemia, serum levels of mucosal enzymes, such as diamine oxidase, may be most likely to indicate intestinal ischemia. Our aim was to compare serum levels of mucosal (diamine oxidase, alkaline phosphatase) and seromuscular (creatinine phosphokinase, lactic dehydrogenase, serum glutamic oxaloacetic transminase) enzymes during intestinal ischemia of varying extent and duration in dogs. Group 1 (n = 6) underwent sham laparotomy. Group 2 (n = 8) had 50% of the small intestine devascularized. Group 3 (n = 8) had the superior mesenteric artery occluded for 2 hours and released. Group 4 (n = 8) had the superior mesenteric artery ligated. Serum samples were obtained before and 2, 4, 8, and 24 hours after operation, and histologic specimens were examined at 4 hours. Creatinine phosphokinase levels became elevated within 4 hours of ischemic injury in group 2 (223 +/- 197 vs. 68 +/- 26, p less than 0.05) and group 4 (212 +/- 136 vs. 76 +/- 29, p less than 0.05). Significant elevation of serum enzymes levels, except diamine oxidase, occurred in groups 2, 3, and 4 at 24 hours, including those with normal histology after temporary superior mesenteric artery occlusion. Thus seromuscular enzymes, particularly creatinine phosphokinase, were more likely to be elevated during intestinal ischemia. Enzyme levels were not influenced by the extent and reversibility of the ischemic injury.
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PMID:Serum enzyme levels during intestinal ischemia. 210 44

In this study, fatty acid binding protein was used to protect an ischemic heart from reperfusion injury. Isolated rat heart was preperfused in the presence of 1.4 microM liposome-bound fatty acid binding protein for 15 minutes, followed by 30 minutes of ischemia and 30 minutes of reperfusion. Our results indicated better preservation of myocardial high-energy phosphate compounds (including ATP and creatine phosphate), reduced creatine kinase and lactate dehydrogenase release from the heart, and improved coronary flow in hearts treated with fatty acid binding protein compared with untreated controls. Fatty acid binding protein enhanced reacylation of arachidonic acid into phospholipids, thereby preserving membrane phospholipids and reducing free fatty acid contents during ischemia and reperfusion. In addition, fatty acid binding protein-bound long-chain free fatty acids and their thioesters as well as carnitine esters were increased in the cytosolic compartment of the heart. These results suggest that fatty acid binding protein may be used as a possible therapeutic agent to improve myocardial function during reperfusion of ischemic heart.
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PMID:Protective role of intracoronary fatty acid binding protein in ischemic and reperfused myocardium. 201 4

We tested the direct effects of thromboxane A2/prostaglandin endoperoxide (TP) receptor agonists and antagonists on ischemic rat hearts to determine if any significant actions of TP may be occurring in a buffer-perfused system (without blood). Buffer-perfused rat hearts were treated with the TP antagonist SQ 30,741 (0.5-1.0 microM) during 15 min of ischemia and 30 min reperfusion. SQ 30,741 had no effect on severity of ischemia. In the same model, the TP receptor agonists U-46619 (0.01-1.0 microM) and SQ 26,655 (0.1 microM) reduced coronary flow and cardiac function both before and after ischemia. The decrease in contractile function appeared to be secondary to flow decrement. Despite the flow effects, U-46619 reduced ischemia-induced lactate dehydrogenase (LDH) release and contracture, indicating some beneficial effects. Measurement of prostacyclin release during reperfusion with and without U-46619 treatment showed that U-46619 significantly increased prostacyclin production. Meclofenamate (5.0 microM) did not reverse the vasoconstrictor and cardiodepressant effects of U-46619 but completely reversed its beneficial effect on LDH release. TP receptor blockade with 1.0 microM SQ 30,741 completely reversed the flow and cardiodepressant effects of SQ 26,655 but did not reverse the beneficial effects of this compound on LDH release. Receptor binding studies using [3H]-SQ 29,548 and [3H]-U-46619 indicated that few if any TP receptors exist in myocytes. In conclusion, TP antagonists are not cardioprotective in this model, but exogenous TP receptor agonists have complex actions in buffer-perfused hearts, some of which are mediated by vascular TP receptors and others which are not.
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PMID:Direct myocardial effects of the thromboxane A2/prostaglandin H2 agonists U-46619 and SQ 26,655 under ischemic and nonischemic conditions. 212 81

The effect of anoxia and reoxygenation on the synthesis and secretion of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was studied in primary cultures of human umbilical vein endothelial cells. Sublethal anoxia, determined by trypan blue dye exclusion and lactate dehydrogenase release, was produced by cell culture under a 95% N2, 5% CO2 atmosphere for 2-24 h and was followed by reoxygenation with 95% air, 5% CO2 for 24 or 48 h. Anoxia did not alter the levels of mRNA for t-PA or PAI-1 in the cells or the secretion of t-PA or PAI-1 into the medium. At 24 h, t-PA secreted into conditioned medium was 7.0 +/- 1.4 ng/2 x 10(6) cells (n = 9) and PAI-1 was 300 +/- 13 IU/2 x 10(6) cells (n = 9), whereas the content of t-PA mRNA was 2.2 pg/micrograms of RNA and PAI-1 mRNA was 180 pg/micrograms of RNA. During reoxygenation, however, t-PA antigen and PAI-1 activity as well as mRNA for PAI-1 decreased proportionally to the duration of anoxia, to reach 27 +/- 1.0, 49 +/- 2.0, and 47 +/- 14% of control values, respectively, within 24 h of anoxia. t-PA mRNA also decreased significantly during reoxygenation following anoxia, but the extent could not be accurately quantitated. Addition, during anoxia, of a 200 micrograms/ml concentration of the superoxide anion radical scavenger superoxide dismutase or of a 5 mM concentration of the iron chelator deferoxamine mesylate prevented the subsequent decrease of t-PA antigen during reoxygenation; addition of these compounds during reoxygenation had no effect. Superoxide dismutase, but not deferoxamine mesylate, when added during anoxia prevented the subsequent decrease in PAI-1 activity. These studies suggest that the marked alteration of endothelial cell fibrinolysis during anoxia followed by reoxygenation is most likely mediated by a mechanism dependent on oxygen radicals. Impaired endothelial cell fibrinolysis may contribute to the pathophysiology of ischemia/reperfusion injury.
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PMID:Oxygen radicals generated during anoxia followed by reoxygenation reduce the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cell culture. 212 75

A number of investigations have implicated free radicals in the progression of ischemic/reperfusion injury. alpha-Tocopherol has been found to attenuate alterations due to ischemia and reperfusion in an isolated heart model. The present study was intended to directly examine neonatal rat cardiac ventricular cell cultures exposed to a free radical generating system catalyzed by xanthine oxidase. The effectiveness of alpha-tocopherol in the attenuation of the resultant changes and the mechanism by which the effects of alpha-tocopherol may be exerted were evaluated. Cultures were either nontreated or pretreated for 18 h with 20 microM alpha-tocopherol or the subcomponents of the alpha-tocopherol molecule, phytol and Trolox. Exposure of cell cultures to free radicals resulted in significant increases in lipid peroxidation products, release of both lactate dehydrogenase and 3H-arachidonate, and structural alterations. Pretreatment with alpha-tocopherol showed significant attenuation of the changes associated with exposure to free radicals. Trolox and phytol at equal molar doses were not as effective as alpha-tocopherol in protecting the myocytes against injury. Thus, alpha-tocopherol seems beneficial in its ability to reduce free radical-mediated changes by functioning as a lipophilic antioxidant. Additionally, the intact, native alpha-tocopherol molecule exceeded the protective capabilities of either of its subcomponents.
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PMID:Free radical damage in neonatal rat cardiac myocyte cultures: effects of alpha-tocopherol, Trolox, and phytol. 212 18


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