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

The effect of regional ischemia on canine myocardial in situ free radical species was studied by the EPR method. Rapid fixation of heart muscle samples by freezeclamping was performed at the following physiological states: native myocardial blood circulation, regional ischemia with the presence of collateral circulation, total ischemia, and postischemic reperfusion. EPR spectra of the samples at -40 degrees C exhibited two free radical signals from the semireduced forms of ubiquinone and flavine coenzymes. Upon transition from normal blood supply to regional ischemia, an increase in the contribution of the flavine signal was registered, but reperfusion resulted in the recovery of the characteristics of EPR signals. It was found that the increase in the intensity of collateral circulation in the ischemic area led to an increase in the portion of ubisemiquinone in the integral EPR signal, whereas in total ischemia this signal was not registered. It was shown that the changes in spectral characteristics of integral free radical signals are accompanied by changes in their relaxation parameters.
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PMID:[Free radical centers in the dog myocardial tissue in regional ischemia]. 1155 87

The multi-subunit mammalian NADH-ubiquinone oxidoreductase (complex I) is part of the mitochondrial electron transport chain and physiologically serves to reduce ubiquinone with NADH as the electron donor. The three-dimensional structure of this enzyme complex remains to be elucidated and also little is known about the physiological regulation of complex I. The enzyme complex in vitro is known to exist as a mixture of active (A) and de-active (D) forms [Biochim. Biophys. Acta 1364 (1998) 169]. Studies are reported here examining the effect of anoxia and reperfusion on the A/D-equilibrium of complex I in rat hearts ex vivo. Complex I from the freshly isolated rat heart or after prolonged (1 h) normoxic perfusion exists in almost fully active form (87+/-2%). Either 30 min of nitrogen perfusion or global ischemia decreases the portion of active form of complex I to 40+/-2%. Upon re-oxygenation of cardiac tissue, complex I is converted back predominantly to the active form (80-85%). Abrupt alternation of anoxic and normoxic perfusion allows cycling between the two states of the enzyme. The possible role in the physiological regulation of complex I activity is discussed.
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PMID:Effect of anoxia/reperfusion on the reversible active/de-active transition of NADH-ubiquinone oxidoreductase (complex I) in rat heart. 1235 Dec 13

Effects of prolonged consumption of ubiquinone on myocardial injury caused by ischemia and reperfusion were studied in reperfused rat hearts. Wistar rats received lipophylic or hydrophilic forms of ubiquinone for 6-8 weeks with chow or water, respectively. Isolated isovolumic hearts with a constant volume latex balloon in the left ventricular cavity were subjected to total normothermic ischemia (25 min) and subsequent reperfusion (50 min). Time course of ischemic contracture and its level in both groups of ubiquinone treated animals were similar to those in controls. However recovery of left ventricular developed pressure after reperfusion was significantly better in both ubiquinone groups (54-/+9, 65-/+7, and 24-/+4 mm Hg in animals treated with lipophylic and hydrophylic ubiquinone and controls, respectively, p<0.01). As a result the developed pressure and heart rate product reflecting maximal aerobic capacity of the heart was also better restored. Both ubiquinone groups demonstrated absence of increased coronary tone that was characteristic for control animals. Mitochondria isolated from reperfused hearts of ubiquinone treated rats showed better preservation of structure and respiratory control. Rate of succinate-dependent generation of superoxide radicals determined with a spin trap TIRON in mitochondria from hearts of rats treated with hydrophylic ubiquinone (35-/+8 mmol O(2) /min/g) was approximately twice lower (p<0.05) than in control group (74-/+12 mmol O(2) /min/g) while the value in lipophylic ubiquinone group (48-/+9 mmol O(2) /min/g) did not differ significantly from the control. The results evidence that prolonged consumption of water-soluble ubiquinone increases resistance of rat myocardium to injuring action of reperfusion.
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PMID:[The protective action of ubiquinone at ischemia and reperfusion]. 1249 19

The purpose of the current study was to investigate aspects of improved bioenergetic function using nicotinamide during stroke. Using a global ischemia-reperfusion mouse model, ATP was depleted by 50% in the brain. The use of nicotinamide to provide a large reserve of brain NAD+ restored ATP levels to 61% of control levels. Alternatively, using nicotinamide as a PARP inhibitor restored ATP levels up to 72%. However, using a large reserve of NAD+ in the brain together with PARP inhibition proved to be additive, restoring ATP to 85% of control levels during the first critical 5 min of reperfusion. NAD+ and ATP levels correlated almost exactly. Brain mitochondrial function was also examined after cerebral ischemia-reperfusion. State 3 respiration of complex I was found to be abolished. However, this was a non-permanent inhibition of activity in vitro, since (NADH ubiquinone oxideroductase) complex I activity in these mitochondria was restored upon the addition of NADH. In vivo, the use of increased brain NAD+ and PARP inhibition was able to partially restore mitochondrial respiration. Taken together, the results show that nicotinamide offers a substantial protective role in terms of preservation of cellular ATP and mitochondrial NAD-linked respiration.
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PMID:Nicotinamide offers multiple protective mechanisms in stroke as a precursor for NAD+, as a PARP inhibitor and by partial restoration of mitochondrial function. 1451 2

The effect of coenzyme Q10 prepared as an oil solution and a water-soluble suspension (the Kudesan preparation) on the resistance of myocardium of Wistar rats to ischemic and reperfusional injuries and the redox state of the components of the cardiac mitochondrial respiratory chain during postischemic reperfusion was studied. Animals received the oil solution of Q10 with food and the Kudesan preparation, with water. It was shown that the drugs, which produce a substantial protective action on the working heart muscle during ischemia and reperfusion, cause a shift of the redox equilibrium between the semireduced forms of ubiquinone and flavine coenzymes to a higher output of ubisemiquinone. With equal doses of the drugs, Kudesan produced a more pronounced effect.
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PMID:[Effect of coenzyme Q10 on free radical centers in isolated rat myocardium tissue]. 1451 92

According to modern images and results of our observations the oxidative stress (OS) is a non-specific though certain component of pathogenesis at numerous diseased states of organism having in the basis the thoroughness of pathogenic disturbances of phospholipids (PL) metabolism and processes of their free radical oxidation (FRO), which takes place in the membrane formations of as the whole cell, as well as the mitochondrial and microsomal fractions (MCF and MSF) of the white rat brain, liver mitochondria, lung shadows, at the same time erythrocyte and lymphocyte shadows at brain acute edema, ischemia, reperfusion and desympathization, infarction of myocardium, tuberculosis of lungs, diabetes, Familial Mediterranean Fever (FMF), intoxications under halothane anaesthesia (HA) and with micotoxin zearalenon. The regularities observed promote to understand from the point of view of modern approaches the molecular mechanisms of initiation, development and generalization of factors for OS formation under pathologic conditions. It is more obvious at zearalenon intoxication with intensification of lipids FRO processes and failures in PL-PL ratio phenomena. The lymphocytes membranes of the white rats spleen subjected OS induced by zearalenon intoxication permit us conclude that the general immune status of the organism decreases. It is generally peculiar to the states under conditions of generalized intoxication. The observed increase of phospholipase A(2) activity induces the release of high concentrations of lysophosphatidylcholines (LPC) and non-etherified fatty acids (NEFA) of polyenic range with prevail of arachidonic acid as a pathogenic factor, namely, at modelling brain acute edema by tetraethylolovo to white rats. Formation of the above mentioned disturbances to some extent depends on hydrophobic properties of toxins, particularly, zearalenon. The latter gives certain tropism to dopamine-beta-monooxygenase (DBM), and ability to stimulate functional activity of the enzyme. Striking haemolytic properties of phospholipase A(2) induced by existence of LPC and NEFA high concentrations, and products of their peroxidation, promote elimination of separate protein fractions of erythrocyte membranes (EM) responsible for OS formation and decrease of erythrocytes resistance to peroxide hemolysis. Increase of DBM activity under the effect of relatively moderate doses of zearalenon (1-15 microg/ml) is accompanied with extra intensification of catecholamine synthesizing function of the organism with lethal result. Data of publications represented testify exceptional efficiency of sodium thiosulfate (STS) as a powerful synergist for endogenous factors of antioxidant effect, particularly alpha-tocopherol (alpha-T), which is the main component for the system of cell antiradical defence. Detoxicating effect of STS can be demonstrated indeed on the example of zearalenon intoxication during the first two hours with the reduction of metabolism disturbances of PL and products of its peroxidation. Comparative evaluation of molecular mechanisms of STS normalizing effect as a supplier for hydrogen and sulphur ions, as well as an effective synergist for alpha-T on the level of various formations of the live cell in compare with the effects of alpha-T and ubiquinone, allowed to make a special accent on the role of STS in interaction with energy-dependent enzymatic systems of cell antiradical defence, as well as accumulation and transformation of energy on the level of mitochondrial membranes. The results obtained by us confirm a number of clinical experimental observations, which demonstrate treatment and prophylactic role of STS at different pathologic states of the organism. STS protectory role at toxic injuries of the organism is higher at its preliminary introduction to the organism before modelling of the studied diseased states, especially at zearalenon and halothane (H) intoxication (in the last case before HA). These data serve a sound affirmation for protectory function of STS, detailed revelation of molecular properties of pathogenesis of the studied intoxication to which a part of our clinical and experimental studies at present is devoted.
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PMID:Oxidative stress in the molecular mechanism of pathogenesis at different diseased states of organism in clinics and experiment. 1572 Feb 41

Brief periods of myocardial ischemia prior to timely reperfusion result in prolonged, yet reversible, contractile dysfunction of the myocardium, or "myocardial stunning". It has been hypothesized that the delayed recovery of contractile function in stunned myocardium reflects damage to one or a few key sarcomeric proteins. However, damage to such proteins does not explain observed physiological alterations to myocardial oxygen consumption and ATP requirements observed following myocardial stunning, and therefore the impact of alterations to additional functional groups is unresolved. We utilized two-dimensional gel electrophoresis and mass spectrometry to identify changes to the protein profiles in whole cell, cytosolic- and myofilament-enriched subcellular fractions from isolated, perfused rabbit hearts following 15 min or 60 min low-flow (1 mL/min) ischemia. Comparative gel analysis revealed 53 protein spot differences (> 1.5-fold difference in visible abundance) in reperfused myocardium. The majority of changes were observed to proteins from four functional groups: (i) the sarcomere and cytoskeleton, notably myosin light chain-2 and troponin C; (ii) redox regulation, in particular several components of the NADH ubiquinone oxidoreductase complex; (iii) energy metabolism, encompassing creatine kinase; and (iv) the stress response. Protein differences appeared to be the result of isoelectric point shifts most probably resulting from chemical modifications, and molecular mass shifts resulting from proteolytic or physical fragmentation. This is consistent with our hypothesis that the time course for the onset of injury associated with myocardial stunning is too brief to be mediated by large changes to gene/protein expression, but rather that more subtle, rapid and potentially transient changes are occurring to the proteome. The physical manifestation of stunned myocardium is therefore the likely result of the summed functional impairment resulting from these multiple changes, rather than a result of damage to a single key protein.
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PMID:Proteomics of ischemia/reperfusion injury in rabbit myocardium reveals alterations to proteins of essential functional systems. 1580 Aug 73

Antinecrotic activity of 2-ethyl-6-methyl-3 oxipyridin succinate (mexidol) and pentoxifylline (trental) was investigated on 32 mail rats with average body-weight of 170-220 g. Under the influence of mexidol and trental, which were injected 15 min before the insection of skin graft and then once per day during 3 days, necrotized area of skin graft is reduced by 22 and 15%, the amount of lost keranocytes--by 33 and 30%. In skin graft homogenates under the influence of mexidol rises the reduced under ischemia succinate dehydrogenase activity, while under trental influence it does not change. Under the influence of mexidol and trental on third day content of ATP rises by 29,5 and 19,5 %, ADP increases and decreases by 27%, creatinphosphate--by 33 and 21% correspondingly. Trentale improves elasticity of erythrocytes. It is suggested, that positive effect of mexidol on skin graft is conditioned by its ability to activate succinate-dependent detour in oxygen phosphorilation chain of mitochondries and to raise content of ubiquinone, whereas the effect of trental relates with intensification of microcirculation, delivery of oxygen on periphery. That allows recommending combined use of preparations in ischemia of skin.
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PMID:[Antinecrotic and antiischemic effect of mexidol and trental in ischemia of the skin graft]. 1598 90

Course treatment with mexidol in a dose of 25 mg/kg for 3 days decreased activities of aspartate transaminase and creatine phosphokinase in the plasma on day 3 after the incidence of skin ischemia (by 1.3 and 1.66 times, respectively). Under these conditions the index of cytolysis decreased by 1.3 times. Therefore, mexidol prevented progression of necrotic processes in the skin. Mexidol therapy of animals with skin ischemia restored the reserve capacity of systems for energy supply and antioxidant defense. The systems of NADH-ubiquinone reductase and succinate-ubiquinone reductase served as the targets for the action of mexidol. Mexidol significantly decreased the damaging effect of reactive oxygen species. Dermatoprotective properties of mexidol were associated with its influence on the energy supply system (regulation of enzyme activity in the electron transport chain, ubiquinone metabolism) and antioxidant defense.
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PMID:Antihypoxic and antinecrotic effect of mexidol in skin ischemia. 1602 7

NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria is a highly complicated, membrane-bound enzyme. It is central to energy transduction, an important source of cellular reactive oxygen species, and its dysfunction is implicated in neurodegenerative and muscular diseases and in aging. Here, we describe the effects of Zn2+ on complex I to define whether complex I may contribute to mediating the pathological effects of zinc in states such as ischemia and to determine how Zn2+ can be used to probe the mechanism of complex I. Zn2+ inhibits complex I more strongly than Mg2+, Ca2+, Ba2+, and Mn2+ to Cu2+ or Cd2+. It does not inhibit NADH oxidation or intramolecular electron transfer, so it probably inhibits either proton transfer to bound quinone or proton translocation. Thus, zinc represents a new class of complex I inhibitor clearly distinct from the many ubiquinone site inhibitors. No evidence for increased superoxide production by zinc-inhibited complex I was detected. Zinc binding to complex I is mechanistically complicated. During catalysis, zinc binds slowly and progressively, but it binds rapidly and tightly to the resting state(s) of the enzyme. Reactivation of the inhibited enzyme upon the addition of EDTA is slow, and inhibition is only partially reversible. The IC50 value for the Zn2+ inhibition of complex I is high (10-50 microm, depending on the enzyme state); therefore, complex I is unlikely to be a major site for zinc inhibition of the electron transport chain. However, the slow response of complex I to a change in Zn2+ concentration may enhance any physiological consequences.
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PMID:The inhibition of mitochondrial complex I (NADH:ubiquinone oxidoreductase) by Zn2+. 1698 Mar 8


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