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)

To examine the effects of nipradilol on ischemic myocardium, experiments were performed on regional myocardial blood flow (MBF) and energy metabolism in anesthetized, open-chest dogs. Nipradilol at a dose of 0.3 mg/kg was i.v.-administered 10 min after coronary ligation. MBFs at various sites, including ischemic and non-ischemic areas, were determined by the hydrogen gas clearance method. The levels of ATP and creatine phosphate (CP) at the site of MBF determination were measured 60 min after ligation, and mitochondrial function (RCI, QO2) in the ischemic and non-ischemic areas was determined. Following nipradilol administration, aortic pressure and heart rate were significantly lowered. In ischemic areas with MBF below 40 ml/min/100 g, nipradilol had no influence on MBF. However, the tissue level of ATP in nipradilol treated hearts was significantly higher as compared with untreated hearts. In the area of mild ischemia with MBF of 40-60 ml/min/100 g, nipradilol preserved the tissue ATP and CP levels in spite of a decrease in MBF. Moreover, an inhibition of the decrease in mitochondrial respiratory function was observed in ischemic areas with MBF below 20 ml/min/100 g. Thus, nipradilol administered following ischemia preserved ATP content and mitochondrial function in the ischemic myocardium with reduction of heart rate and aortic pressure. This suggests that nipradilol exerts a cardioprotective effect in acute ischemia. It seems that the cardioprotective effect is due to a decrease in myocardial oxygen demand and preservation of mitochondrial function.
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PMID:Beneficial effect of nipradilol (K-351) on acute myocardial ischemia. Study of the relationship between regional myocardial blood flow and energy metabolism. 196 87

To assess the effects of left ventricular chamber volume on the mechanism of changes in left ventricular developed pressure we performed phosphorous-31 nuclear magnetic resonance spectroscopy, hydrogen-1 nuclear magnetic resonance spectroscopy with a shift reagent, two-dimensional echocardiography, atomic absorption spectrophotometry, microsphere analysis, and surface fluorometry on isovolumic isolated perfused rat hearts with incremental intraventricular balloon volumes, while left ventricular pressure was concurrently monitored. A three-phasic response of developed pressure was noted: 0 to 100 microliters balloon volumes resulted in an increase in developed pressure, whereas developed pressure remained constant at 250 microliters and fell at 400 microliters. Oxygen consumption and [Ca2+]i transients followed the same pattern as developed pressure and coronary flow. Intraventricular volumes of 250 microliters or greater (a volume overload) caused endocardial ischemia, a greater decrease in extracellular versus intracellular water, thinning of the left ventricular free wall, and an increase in chamber size. Mechanical pressure on the tissue, induced by the volume overload, caused ischemia as further evidenced by (1) a negative effect on developed pressure, (2) a decrease in [Ca2+]i transients, (3) a [Ca2+]i overload, (4) a moderate decrease in the phosphorylation potential, and (5) an increase in the oxidation-reduction state (nicotinamide-adenine dinucleotide). The high intracellular calcium associated with volume overload may have been due to both compression and ischemia, which leads to an increased number of cross-bridges in rigor, a high end-diastolic pressure, and an increase in wall stress.
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PMID:Mechanism for depressed cardiac function in left ventricular volume overload. 199 Jul 59

Reoxygenation injury that occurs when blood circulation is restored to previously ischemic tissues is currently discussed as a pathophysiological entity distinct from the primary anoxic injury that develops during ischemia per se. To test the hypothesis that reoxygenation injury in hepatocytes is caused by a postischemic burst of reactive oxygen species (ROS), including superoxide radicals, O2-., and hydrogen peroxide, H2O2, we performed a cytochemical study exploiting the peroxidase activity within peroxisomes as a sensitive ultrastructural detector of intracellular H2O2 generation. The osmiophilic polymer formed when tissue peroxidase is incubated with 3,3'-diaminobenzidine (DAB) and H2O2 was used as a marker for endogenous H2O2 in rat liver slices in short-term organ culture subjected to a cycle of 60-min ischemic anoxia and 30-min reoxygenation in the presence of DAB without exogenous H2O2. Peroxisomal reaction product was quantitatively evaluated in transmission electron micrographs of systematically sampled hepatocytes. Mean densities of positive peroxisomes per 1,000 micron2 (+/- SE) in liver slices subjected to various treatments were as follows: continuous anoxia (negative control) 0 +/- 0; normoxia + exogenous H2O2 (positive control) 45 +/- 12; normoxia only 26 +/- 2; ischemia-reoxygenation 13 +/- 6; ischemia-reoxygenation + xanthine oxidase inhibitor, oxypurinol 5 +/- 3; ischemia-reoxygenation + peroxidase inhibitor, aminotriazole 7 +/- 3. Endogenous H2O2 can be detected in hepatocytes by electron microscopic cytochemistry and may in part derive from xanthine oxidase, but it is not substantially increased in the postischemic state. We conclude that hepatocytes do not exhibit a postischemic burst of reactive oxygen species that could cause reoxygenation injury.
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PMID:Cytochemical studies of hydrogen peroxide generation in postischemic hepatocytes. 199 89

Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent.
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PMID:Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. 199 54

Using a highly specific assay that minimizes enzyme inactivation in vitro, we found that rabbit myocardial tissue contained low levels of xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity that were effectively inhibited by pretreatment of hearts with allopurinol. In parallel, allopurinol treatment also improved ventricular developed pressure, peak systolic pressure, and coronary flow in isolated hearts subjected to 30 min of normothermic global ischemia and 30 min of reperfusion. Although function was protected by allopurinol treatment, creatine kinase (CK) release was not altered by allopurinol. Inhibition of myocardial XO with allopurinol did not increase myocardial ATP or phosphocreatine. In addition, allopurinol did not scavenge superoxide anion or hydrogen peroxide in vitro. The results support the possibility that relatively low amounts of XO activity, similar to levels reported in human myocardium, may contribute to cardiac ischemia-reperfusion injury.
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PMID:Existence and participation of xanthine oxidase in reperfusion injury of ischemic rabbit myocardium. 200 Sep 75

Cytotoxicity resulting from the interaction of fluorescent light from a flow hood with Hepes-buffered cell culture medium at room temperature was demonstrated. Toxicity was prevented by keeping both cells (V79 Chinese hamster) and medium shielded from direct fluorescent light ("dark conditions") or by supplementing the medium with 10 micrograms/ml catalase; this suggests that extracellular hydrogen peroxide is a major cause of the lethal effect under "lighted conditions." No sensitization resulted from the exposure of cells in a sodium bicarbonate (SBC)-buffered medium to fluorescent light, nor in a catalase supplemented SBC-buffered medium. The Hepes/light reaction during routine cell manipulations presensitized cells to hypothermia damage in the dark with the presensitization being more severe for 5 than for 10 degrees C hypothermic exposure. Presensitization was prevented by performing the complete experiment under dark conditions or by supplementing the medium with 10 micrograms/ml catalase. However, catalase did not improve the hypothermic survival when experiments were performed under dark conditions. Hence, 10 micrograms/ml catalase does not protect cells from hypothermic (5 and 10 degrees C) damage per se, but rather from Hepes/light sublethal damage which interacts with hypothermic sublethal damage to result in lethal lesions. Additionally, under dark conditions, superoxide dismutase (SOD), allopurinol, catalase plus SOD, DMSO, or mannitol did not improve survival when present during hypothermic storage, suggesting that extracellular superoxide anion, hydrogen peroxide, or hydroxyl radicals are not the cause of cell killing under conditions of pure hypothermia uncomplicated by prehypothermic ischemia or hypoxia.
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PMID:Factors influencing survival of mammalian cells exposed to hypothermia. V. Effects of hepes, free radicals, and H2O2 under light and dark conditions. 201 62

We examined the effect of intravenous infusion of graded doses of authentic leukotriene (LT) C4 on several physiological variables in pentobarbital-anesthetized immature swine. Mesenteric blood flow (Qsma) was measured using an ultrasonic flow probe and ileal intramucosal hydrogen ion concentration ([H+]I) was estimated tonometrically. Three groups were studied. Pigs in Group I (n = 6) were infused beginning at t = 0 min with increasing doses (0.03-1.0 microgram/kg-min) of LTC4, each dose being administered for 10 min. Pigs in Group II (n = 6) were infused with LTC4 as above, but were pre- and post-treated with a specific sulfidopeptide LT receptor antagonist, LY203647 (30 mg/kg bolus and then 10 mg/kg-hr) beginning at t = -20 min. Pigs in Group III (n = 4) received only normal saline (5 ml/kg-h). Infusing LTC4 significantly decreased Qsma and mesenteric oxygen uptake and significantly increased ileal [H+]I. These changes were prevented by LY203647. These data support the idea that sulfido-peptide LT are capable of causing mesenteric ischemia and that this phenomenon can be blocked by LY203647.
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PMID:Leukotriene C4 induces mesenteric hypoperfusion and intestinal intramural acidosis in pigs. 202 Jan 83

Free radicals may arise from a number of sources as a result of a variety of cellular mechanisms; they are generated under both normal and pathological circumstances. The xanthine oxidase pathway, the arachidonic acid pathway, invading leucocytes, catecholamine oxidation, and mitochondrial activity can all lead to the production of a variety of reactive oxygen intermediates including superoxide, hydrogen peroxide, and the hydroxyl radical. Whatever their source, free radicals can be extremely toxic to the cell and they are capable of causing major membrane injury by initiating lipid peroxidation or by altering the activity of membrane-bound enzyme systems which control ionic movement. The cell possesses highly efficient protective mechanisms, including antioxidants such as vitamins C and E and the enzymes superoxide dismutase and catalase, all of which are designed to prevent the occurrence of free radical-induced injury under normal conditions. However, during ischaemia and reperfusion, these protective mechanisms may be overwhelmed and severe free radical-mediated injury may occur. Ischaemia may prime the myocardium for free radical-induced injury. The great majority of the evidence that manipulation of free radicals may protect against such injury is, however, circumstantial.
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PMID:Free radicals and the heart. 202 51

From in vitro studies involving multilamellar liposomes or other artificial systems, several groups of workers have deduced that Trolox (a water-soluble analogue of vitamin E) and ascorbate are synergistic antioxidants. Here, we demonstrate that while Trolox and ascorbate individually protect cultured hepatocytes against oxyradicals generated either with xanthine oxidase plus hypoxanthine or with hydrogen peroxide, the two antioxidants do not appear to be synergistic when used in equimolar combinations. Also, in a rat model of hepatic ischemia-reperfusion, we observed that infusion of Trolox or ascorbate (7.5-10 mumol/kg body weight) into the postischemic liver reduced the reperfusion injury by 76 or 67%, respectively. However, when both compounds were used together (each at the same dose as used separately), the organ salvage amounted to only 79%. Therefore, there is no evidence of synergism between Trolox and ascorbate in our in vitro and especially in vivo systems.
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PMID:Trolox and ascorbate: are they synergistic in protecting liver cells in vitro and in vivo? 203 21

A vast amount of circumstantial evidence implicates oxygen-derived free radicals, especially superoxide and hydroxyl radical (and to lesser extent, hydrogen peroxide), as mediators of inflammation and/or tissue destruction in inflammatory and arthritic disorders. The substrates for radical generation, namely properly stimulated phagocytic cells, transition metal catalysts, and (to a limited extent) ischemia, are all amply present, although there is no particular rheumatic disease in which a consistent abnormality of radical generation has been identified. These radical species can clearly degrade hyaluronic acid, modify collagen and perhaps proteoglycan structure and/or synthesis, alter and interact with immunoglobulins, activate enzymes and inactivate their inhibitors, and possibly participate in chemotaxis. In most situations, however, there is ample scavenging ability to detoxify these radicals before they hit their target, and many rheumatic disease drugs can decrease their production and/or effects. Despite the apparent sufficiency of natural scavengers and the lack of direct evidence that oxygen radicals are pathogenetically important, substantial pharmaceutical effort is still being made to develop free radical scavengers as therapeutic agents. Although individual free radicals die out quickly, rheumatologic interest in them has been sustained for nearly two decades.
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PMID:Oxygen radicals, inflammation, and arthritis: pathophysiological considerations and implications for treatment. 204 55


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