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

Ischaemia/reperfusion of cardiac tissue has been claimed to be associated with the production of oxygen free radicals, which can contribute to severe membrane damage and tissue injury. We investigated the effects of anoxia/reoxygenation treatment on superoxide radical production in an in vitro system consisting of preconfluent and confluent human endothelial cell monolayers. The influence of varying the anoxia and reoxygenation phases on superoxide production was studied. As a test of cytotoxicity, the release of the cytosolic enzyme lactate dehydrogenase in the culture medium was measured before and at 0, 24 and 48 h after anoxia-reoxygenation. Cellular damage was monitored by microscopic examination of the cultures during and after the experiments and by the expression of the von Willebrand protein and of the membrane glycoprotein IIa by indirect immunofluorescence with specific monoclonal antibodies. Our results show that the endothelial cells subjected to anoxia-reoxygenation release superoxide anions, as revealed by superoxide dismutase inhibitable cytochrome C reduction. Free radical production is dependent on cell confluent or preconfluent state and on both anoxia and reoxygenation duration. Free radical release does not seem to be accompanied by manifest cellular alteration.
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PMID:Superoxide production by human umbilical vein endothelial cells in an anoxia-reoxygenation model. 255 Jan 29

In the control perfused working rat hearts subjected to 25 min global ischemia, reperfusion resulted in a 50% recovery of the hemodynamic functions. A concentration-dependent improvement of this recovery and a reduction of the postischemic lactate dehydrogenase (LDH) release was caused by calmidazolium (CMZ), trifluoperazine (TFP), and chlorpromazine (CPZ) added prior to ischemia. The drugs were not effective when added only to the reperfusate. The concentrations of CMZ, TFP, and CPZ producing the half-maximal effects were 2.5 X 10(-9) M, 1.5 X 10(-7) M and 3 X 10(-7) M, respectively. Prolongation of the ischemic period caused a progressive deterioration of the functional recovery of the hearts while the total postischemic LDH release showed, at the same time, an initial gradual rise followed by a later decay. In untreated hearts the duration of ischemia resulting in 50% loss of hemodynamic function and in a maximal LDH release was 25 min. TFP (10(-6) M) and CMZ (10(-7) M) prolonged these times by 4-7 min and 5-10 min. respectively. TFP, CPZ, and CMZ protected the erythrocytes from osmotic hemolysis. The maximum anti-hemolytic activity was produced by 3 X 10(-6) M CMZ, 3 X 10(-5) M TFP, and 10(-4) CPZ. The concentration-dependency of this effect was not affected by low concentrations of sodium dodecyl sulphate (SDS). Neither TFP nor CMZ prevented the hemolysis produced by 10(-3) M SDS. It is concluded that the delay in the development of the ischemic injury produced by TFP and CMZ is due to the effects of these drugs as calmodulin antagonists rather than as membrane stabilizers.
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PMID:Anti-ischemic and membrane stabilizing activity of calmodulin inhibitors. 261

Captopril, an angiotensin converting enzyme inhibitor, has been shown to increase prostaglandin production by an as yet unknown mechanism, which this study was designed to explore. Isolated rat heart was perfused by the Langendorff technique for 15 minutes in the presence or absence of captopril. Ischemia was then induced for 60 minutes by terminating the coronary flow, followed by 60 minutes of reperfusion. Our results indicate that captopril stimulated prostaglandin and thromboxane production, but it inhibited malonaldehyde formation. Coronary flow and high energy phosphate compounds were increased, but lactate dehydrogenase and creatine kinase release decreased, demonstrating cardioprotective effects. Captopril also inhibited the production of hydroxyl radical in the heart during reperfusion, suggesting that stimulated prostaglandin production may be linked with the generation of free radicals via the eicosanoid system.
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PMID:Enhanced prostaglandin production in the ischemic-reperfused myocardium by captopril linked with its free radical scavenging action. 269 79

For the validation of volume-selective 1H and 31P NMR spectroscopy of the brain methods are required that allow high resolution quantitative mapping of tissue pH and metabolites on intact brain slices. The following techniques are proposed for this purpose. Tissue pH is imaged on cryostat sections of in situ frozen brains, using umbelliferone as a fluorescent pH indicator (Csiba et al, Brain Res 289, 334-337 (1983]. Regional tissue ATP content is measured in adjacent cryostat sections, using the luciferine/luciferase system of fireflies for evoking substrate-specific bioluminescence (Kogure and Furones Alonso, Brain Res. 154, 273-284 (1978]. Lactate content is imaged in a similar way by inducing substrate-specific bioluminescence with lactate dehydrogenase and luciferase from vibrio Fischeri (Paschen, J. Cereb. Blood Flow Metab. 5, 609-612 (1985]. The spatial resolution of these techniques is better than 100 mu, as exemplified in experimental brain tumors and brain infarct of cats. The applicability of biochemical mapping for the validation of NMR spectroscopy was tested in a global brain ischemia model of cat by correlating surface coil 31P and 1H spectra with the corresponding regional biochemical data, measured in the sensitive volume of the coil. Correlation coefficients were r = 0.907, 0.852 and 0.924 for pH, lactate and ATP, respectively. These results demonstrate that the biochemical measurements obtained by bioluminescence and fluoroscopic imaging correlate closely with the NMR data and, therefore, are appropriate for the validation of more complex applications, such as volume-selective spectroscopy of brain infarcts or tumors.
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PMID:Imaging of brain tissue pH and metabolites. A new approach for the validation of volume-selective NMR spectroscopy. 270 7

Myocardial ischemia and reperfusion have been shown to result in damage to the phospholipid components of cardiac myocyte cell membranes as indicated by the tissue accumulation of unesterified fatty acids (UFA). A portion of this damage and subsequent dysfunction may be a consequence of free radical-induced membrane lipid peroxidative events. alpha-Tocopherol, a lipophilic antioxidant, was used in this study as an agent by which the extent of ischemia and reperfusion injury might be decreased. Increasing rat myocardial tissue levels of alpha-tocopherol by 51% was found to attenuate lipid perturbations as determined by the accumulation of tissue UFA in an isolated heart model of global ischemia and reperfusion. Nontreated hearts made ischemic for 25 min with 30 min of reflow had a significantly increased total UFA level of 5,961 +/- 799 nmol/mg protein (P less than 0.05) compared with control perfused hearts containing 3,116 +/- 463 nmol UFA/mg protein and with alpha-tocopherol-treated ischemic and reperfused hearts containing 3,066 +/- 365 nmol UFA/mg protein. Contractile dysfunction, excessive accumulation of tissue calcium, and release of lactate dehydrogenase after ischemia and reperfusion were also reduced, demonstrating protective effects in alpha-tocopherol-treated hearts. Thus alpha-tocopherol proved effective in the attenuation of ischemia and reperfusion damage. These results suggest that reducing lipid alterations may prove beneficial in protecting against membrane damage subsequent to ischemia and reperfusion.
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PMID:alpha-Tocopherol attenuates myocardial membrane-related alterations resulting from ischemia and reperfusion. 270 58

The model of interrupted ischemia of the isolated heart has been used to show that the yield of lactate dehydrogenase into perfusate in experiments on old rats is described by more sharply pronounced S-like dependence than that in young immature animals. The activation of lipid peroxidation precedes the sarcolemma damage and is relatively more manifested in rats of middle and old age. The respiratory control of mitochondria (in homogenates) decreases considerably already 20 min after ischemia, however mitochondria retain their ability to synthesize ATP 3 h later as well. The causal-effect relationship between the activation of lipid peroxidation and partial disturbance of the mitochondrial function remains unclear.
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PMID:[Features of ischemic injuries to membranes and activation of lipid peroxidation in the myocardium of rats of various ages]. 272 20

In this study, we investigated the role of oxygen-derived free radicals and iron in mediating myocardial injury during ischemia and reperfusion. Iron is of special interest because it may enhance tissue injury during ischemia and reperfusion by catalyzing the formation of highly reactive hydroxyl radicals (by modified Haber-Weiss or Fenton reactions). Rat hearts, perfused by the Langendorff method, were subjected to global ischemia (15 minutes at 37 degrees C) and reperfusion. The effects of two iron chelators, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and 5-hydroxy-2-hydroxymethyl-4-pyrone (kojic acid), and one antioxidant, (+)-cyanidanol-3, on contractile function, coronary flow, lactate dehydrogenase release, and lactate production were studied. The combination of these iron chelators is of special importance because L1 is known to prevent lipid peroxidation, induced by ADP/Fe3+ and NADPH in microsomes, in contrast to kojic acid. We found significant protection of contractile function (apex displacement) during reperfusion with 50 microM L1 and 20 microM (+)-cyanidanol-3 (p less than 0.01, n = 6), whereas no protection was found with 50 microM kojic acid (n = 6). Measurements of lactate dehydrogenase release during reperfusion showed a protective pattern similar to that found for heart contractile function, although 50 microM kojic acid also showed a significantly lower lactate dehydrogenase release during the first 10 minutes of reperfusion. No differences in coronary resistance or lactate release were found between the various groups. Our findings indicate that iron and oxygen-derived free radicals are important in the pathogenesis of postischemic reperfusion injury probably because of the formation of hydroxyl radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3. 273 47

Preincubation of rat myocardial cells in hypoxic substrate-free Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) resulted in a substantial decline in high energy phosphates (ATP and CP). Thus, 20 and 60 min preincubation produced a 18 and 72% decline in ATP content, whereas the parallel decline in CP content was 51 and 73%. This energy depletion was accompanied by a change in cell morphology from the initial rod-shaped form to rounded up (hyper-contracted) myocytes. In cells preincubated in substrate-free normoxic buffer, both normal morphology and energy homeostasis were maintained. When energy depleted myocytes later were incubated in the presence of phospholipase C (PLC), this resulted in a substantial release of glycerol, amounting to 92 and 137 nmol/10(6) cells.2 h in 20 and 60 min energy depleted myocytes, respectively. In addition, PLC caused an increased leakage of lactate dehydrogenase in energy depleted myocytes. Normal cells, on the other hand, were apparently not affected by PLC. These data suggest that PLC selectively attacks energy depleted and/or structurally damaged myocytes. This could well enhance the breakdown of the natural barrier between the extra- and intracellular compartments and thus augment the cellular damage during ischemia. Moreover, energy depleted myocytes appeared exceptionally sensitive to this enzyme, since the levels required to cause glycerol or lactate dehydrogenase release were several orders of magnitude lower than that required to cause membrane permeation in other cell types.
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PMID:Phospholipase C-evoked glycerol release in energy depleted rat myocardial cells. 277 31

Disturbances in lipid metabolism may play an important role in the onset of irreversible myocardial damage. To investigate the effect of ischemia and reperfusion on lipid homeostasis and to delineate its possible consequences for myocardial damage, Krebs-Henseleit-perfused, working rat hearts were subjected to various periods of no-flow ischemia (10 to 90 minutes) with or without 30 minutes of reperfusion. During ischemia, the rise in nonesterified fatty acids (NEFAs) was preceded by the accumulation of substantial amounts of glycerol, indicating the presence of an active triacylglycerol-NEFA cycle. The subsequent rise in NEFAs (from 0.25 to 1.64 mumol/g dry residue wt after 90 minutes [means]) coincided with the reduction of ATP to values lower than 10 mumol/g dry wt and the rise of AMP, a potent inhibitor of acyl-coenzyme A synthetase, to values exceeding 2 mumol/g dry wt, making the latter compound a good candidate to hamper the turnover of endogenous lipids during prolonged ischemia. Reperfusion resulted in an additional rise in NEFAs (up to 4.1 mumol/g dry residue wt after 60 minutes of ischemia). Neither ischemia nor reperfusion resulted in significant decreases in the tissue content of triacylglycerols and the various phospholipids. During reperfusion recovery of stroke volume was still adequate at tissue NEFA levels thought to be incompatible with normal mitochondrial function. A positive correlation (r = 0.81) was found between NEFA content of reperfused hearts and cumulative release of lactate dehydrogenase during reperfusion. Accordingly it is concluded that 1) reperfusion results in additional changes in myocardial lipid homeostasis, 2) the accumulating NEFAs are compartmentalized, possibly at the cellular level, and 3) the accumulation of NEFAs is a sensitive marker for myocardial cell damage.
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PMID:Lipid alterations in isolated, working rat hearts during ischemia and reperfusion: its relation to myocardial damage. 278 64

The lactate dehydrogenase (LDH) activity and LDH isozyme ratio in the perfusate were investigated in perfused dog kidneys, preserved from dogs subjected to warm ischemia of varying duration prior to kidney removal. The length of this warm ischemic time exerted a marked effect on the variations in both the LDH activity and isozyme ratio. Moreover, the variations in LDH activity and isozyme ratio during the preservation were found to correlate well. On this basis, the M-component activity of the LDH isozymes and the activity of the LDH4 and LDH5 isoenzymes are proposed to represent more sensitive parameters for evaluating the tissue hypoxic damage. Our data were also analyzed retrospectively, in relation to the ability of the perfused kidney to function on autotransplantation. It was found that the amount of LDH4 and LDH5 isoenzyme activity was of great value in determining the viability of the kidney. Thus, an analysis of the LDH activity in the wash solution can provide considerable and precise information about the kidney viability as a graft.
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PMID:Viability estimation of preserved dog kidneys based on the LDH activity in the preservation perfusate. 279 93


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