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

The article deals with oxidation of different substrates, intensity of glycolytic and glycogenolytic processes in mitochondria and homogenates of dog liver with its 2-hour exclusion from circulation under conditions of endotracheal ether-oxygen narcosis. It was established that already 30-60-minute ischemia causes a decrease in intensity of succinate, alpha-ketoglutarate oxidation and acceptor respiration, inhibiton in the activity of the citrate cycle enzymes; succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, isocytrate dehydrogenase. The activity of NAD-dependent malate dehydrogenasedehydrogenase and Mg2+-ATPase as well as intensity of NADN oxidation in mitochondria increase. After 2-hour ischemia the activity of Mg2+-ATPase, cytochrome oxidase and peroxidase lowers. A sharply developed glycogenolysis is accompanied by inhibition of phosphorylase activity and a two-fold stimulation of the glycolytic reactions. Peculiarities in regulation of enzymatic reactions under conditions of ischemia and their role in origin of metabolism disturbances in the liver are under discussion.
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PMID:[Carbohydrate metabolism in the liver in acute ischemia]. 17 60

Heart muscle mitochondria with satisfactory functional parameters of oxidative phosphorylation and with morphologically intact structure were isolated from canine myocardium employing a modified KEA-medium (0.18 M KCl, 10 mM EDTA, 0.5% bovine serum albumin, pH 7.1) according to Sordahl and Schwartz (1). The functional behaviour of mitochondria was investigated after different durations of in situ ischemia (cardioplegia, 15 degrees C) and correlated with metabolic findings. During ischemia the following changes were seen: 1. Successive reduction of electron flow. 2. Relatively small impairment of phosphorylation efficiency. 3. Less damage of FAD- than NAD-catalyzed oxidative phosphorylation. 4. A marked increase of electron flow and thus recovery of phosphorylation rate even after longer ischemic periods by addition of cytochrome c. As important factors of accelerating mitochondrial impairment during ischemia the myocardial ATP decrease, the lactate and H+-activity increase are discussed.
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PMID:Functional behaviour of isolated heart muscle mitochondria after in situ ischemia. Polarographic analysis of mitochondrial oxidative phosphorylation. 20 84

The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance.
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PMID:Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture. 22 Nov 34

Under study were morphological changes in the gastric mucosa in 40 patients with the syndrome of abdominal ischemia due to a varying degree of stenosis of the celiac artery, and in 8 patients without any changes in the celiac artery. In 10 cases the mucous membrane was studied histoenzymologically. In a marked stenosis of the celiac artery there was observed an atrophy of the mucosa and decreased general activity of succinate-, lactate, and NAD-N-dehydrogenases on account of a decreased number of cells, in which these enzymes are revealed. In early stages of the disease restoration of blood flow would result in normalization of the mucous membrane structure.
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PMID:[Functional morphology of gastric mucosa in the syndrome of celiac artery stenosis before and after decompression]. 122 38

Neurotrophic factors regulate neuronal survival and neurite growth in development and following injury. Oxidative stress produced in neurons as a consequence of primary injury, or during reperfusion following ischemia, may contribute to cell death. Here, the effects of nerve growth factor (NGF) on the response to H2O2 injury were examined in the PC12 rat pheochromocytoma cell line. Specifically, the effect of NGF on cell viability after H2O2 injury was measured. Pretreatment with NGF enhanced survival after H2O2 treatment, as measured by Trypan blue dye exclusion, radiolabeled amino acid incorporation, tetrazolium salt reduction, or cytoplasmic enzyme release. One early event associated with H2O2 treatment was a rapid decrease in NAD+. Although initial decreases in NAD+ levels were similar in control and NGF-treated cells, the latter recovered more rapidly and extensively. The decline in total NAD observed after NGF treatment was almost equal in magnitude to the measured increase in NADP. Inhibition of poly(ADP-ribose) polymerase also enhanced viability following H2O2 injury. Treatment with both NGF and an inhibitor of this enzyme resulted in a greater reduction of H2O2 toxicity than was observed with either agent alone. These data suggest that NGF protection is multifactorial and that a significant component of the NGF effect is due to its regulatory role in the metabolism of pyridine nucleotides.
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PMID:Nerve growth factor effects on pyridine nucleotides after oxidant injury of rat pheochromocytoma cells. 145 Sep 13

Isolated working rat hearts were subjected to aerobic perfusion (25 min), cardioplegic infusion (3 min), global ischemia (30 min at 37 degrees C) and reperfusion (35 min). Measurements of myocardial xanthine oxidase and dehydrogenase activity, together with various adenine nucleotides and metabolites, were made at defined stages of the protocol (n = 6/group). Allopurinol pretreatment (20 mg/kg body wt/day for 3 days) improved the postischemic recovery of cardiac function; thus, aortic flow (a representative index) recovered to 68.8 +/- 4.2% compared with 53.2 +/- 2.3% in untreated controls (p less than 0.05). In fresh tissue, allopurinol pretreatment inhibited xanthine dehydrogenase activity by 73.1% (from 11.9 +/- 0.5 to 3.2 +/- 0.8 mIU/g wet wt: p less than 0.05) and xanthine oxidase activity by 95.2% (from 8.3 +/- 1.2 to 0.4 +/- 0.2 mIU/g wet wt: p less than 0.05); however, this inhibition was not maintained during perfusion. During reperfusion, myocardial xanthine dehydrogenase and oxidase activity was reduced by 40-60% (p less than 0.05) in both allopurinol pretreated and control hearts. Tissue content of creatine phosphate, adenosine triphosphate and catabolites, NAD and inorganic phosphate were not different in allopurinol pretreated or control hearts during either ischemia or reperfusion. This study does not support the concept that allopurinol protects the rat heart during ischemia and reperfusion by inhibition of xanthine oxidase activity or by conservation of purines. It appears that allopurinol achieves its protective effects by some, as yet undefined, mechanism.
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PMID:Allopurinol-enhanced myocardial protection does not involve xanthine oxidase inhibition or purine salvage. 152 Feb 48

The three-vessel occlusion model of Kameyama et al. (Kameyama, M., Suzuki, J., Shirane, R. and Ogawa, A. (1985) Stroke 16, 489-493) was adapted with modifications to induce complete reversible rat forebrain ischemia. A fast and simple procedure for the isolation and purification of rat brain mitochondria, which provides high yield, is described. Mitochondria isolated from ischemic brain (12-30 min ischemia) exhibited decreases in State 3 respiratory rates of approx. 70% with NAD-linked respiratory substrates. Less effect was observed with succinate and rotenone. The State 4 respiratory activity remained near control levels except at 15 min of ischemia (25% increase) with NAD-linked substrates. Similarly, with succinate and rotenone, an approx. 30% increase in State 4 activity was observed at 20 min of ischemia. Consequently, the respiratory control indices (RCIs) were decreased. Both the respiratory rates and RCIs could be restored to near control levels upon the addition of EGTA(EDTA) or ruthenium red to the assay mixture. Analysis employing fura-2 as a Ca2+ probe, indicated a great decrease in the first order rate constant for Ca2+ uptake of ischemic mitochondria and a significant increase in Ca2+ homeostasis with an increase in the cytosolic Ca2+ concentration which results in excessive association of Ca2+ on the mitochondrial membrane and an inhibition of the respiratory chain-linked oxidative phosphorylation and Ca(2+)-transport activity of forebrain mitochondria. These deficits are proportional to the duration of ischemia.
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PMID:Ischemic injury to rat forebrain mitochondria and cellular calcium homeostasis. 155 46

The dramatic increase in the arachidonic acid (AA) level in the brain is a well-known molecular event during cerebral ischemia. As mitochondria are known to be one possible site of the cell damage, the effects of AA on the respiratory activity of rat brain mitochondria were investigated in vitro using an oxygen electrode. In NAD-linked respiration, respiratory control ratio was decreased significantly by AA, with an IC50 of 6.0 microM. AA had the dual effect on mitochondrial respiration, a decrease in state 3 and uncoupled state and an increase in state 4 (i.e., uncoupling) as reported by Hillered and Chan (J. Neurosci. Res. 19, 94-100, 1988). Furthermore, we found that other unsaturated long-chain free fatty acids (C18:1-C18:3, C20:1-C20:5) also showed such a dual effect. Cyclooxygenase metabolites of AA such as prostaglandins (D2, E2, F2 alpha, E1) and thromboxane B2, and lipoxygenase metabolites such as leukotrienes (D4, B4) and 5- or 12-hydroperoxyeicosatetraenoic acid had no significant effect. The inhibition of the uncoupled state by AA was more marked in NAD-linked than that in FAD-linked respiration, while the degree of uncoupling by AA were the same in both respirations. In spectrophotometrical measurement, the reduction of cytochromes and flavo-protein was markedly inhibited by AA in NAD-linked respiration, but not in the FAD-linked one. In addition, the activity of cytochrome c oxidase was scarcely inhibited by AA. These data suggest that AA itself, not its metabolites, may inhibit mitochondrial ATP production during brain ischemia and that AA may act on the site(s) closely related to NAD-linked respiration, but not the FAD-linked one, in addition to its uncoupling effect.
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PMID:A possible mechanism of mitochondrial dysfunction during cerebral ischemia: inhibition of mitochondrial respiration activity by arachidonic acid. 165 47

The loss of NADH-ubiquinone oxidoreductase activity, the activity of mitochondrial electron transfer complex I, underlies the loss of mitochondrial phosphorylating respiration with NAD-linked substrates observed during myocardial ischemia. In the present study the loss of complex I activity was found to be considerably more rapid during zero-flow ischemia in rat heart, a fast heart-rate heart, than in dog heart, a slow heart-rate heart. Moreover, the greater rapidity of the loss of complex I activity in the ischemic rat heart appeared to reflect the more rapid and more severe decreases in tissue pH and in tissue ATP characteristic of the zero-flow ischemic rat heart compared to zero-flow ischemic dog heart. In vitro enzyme inactivation studies on dog heart electron transfer complex I showed that the enzyme was approximately 40% inactivated after 1 minute by incubation at pH 6.0 in the absence of added ATP. The effect of low pH upon enzyme activity was mitigated considerably by the presence of one to two mM MgATP in the incubation mixtures. Moreover, a portion of the activity-sparing effect of MgATP was still observed in the presence of the uncoupler, FCCP. This latter observation suggests that part of the function-stabilizing effect of ATP was attributable to inner membrane energization and part appeared to have been due to a direct protective effect of ATP upon the complex.
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PMID:Effects of acidosis and ATP depletion on cardiac muscle electron transfer complex I. 174 4

The recovery of both contractile performance and metabolic response of rat heart following 1 h of ischemia after equilibration with glucose + insulin (glucose-ischemia) or with pyruvate (pyruvate-ischemia), was tested in normoxic reperfusion in the presence of glucose + insulin, pyruvate, lactate or acetate. In glucose-ischemia only the reperfusion with pyruvate results in a complete recovery of the contractile force (left ventricular pressure, LVP) (170%) and good recovery of high energy phosphate compounds. Lower LVP and tissue energy charge were found in glucose reperfusion and even less in lactate and acetate reperfusion. Disappearance of the IMP accumulated during ischemia is evident only in the pyruvate reperfusion indicating a higher metabolic recovery. On the contrary in pyruvate-ischemia all types of reperfusion tested were effective in reactivating the contractile force (although acetate to a lesser extent); the contractile activity was accompanied by a good recovery of phosphocreatine, ATP, energy charge and by the decrease of IMP. Large decreases of adenine nucleotides and NADP and lower decreases of NAD are observed during ischemia/reperfusion in both systems. Pyruvate-ischemia is quite similar to, if not worse than glucose-ischemia, for all the metabolic parameters considered, but not worse for the possibility of recovery. Some specific effect of pyruvate should be exerted during the ischemic phase. The mechanism of pyruvate protection is discussed in relationship to: (i) the possible activation of pyruvate dehydrogenase, (ii) the activation of NADPH-dependent peroxide scavenging systems, (iii) the direct scavenging action of pyruvate on H2O2.
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PMID:The protective action of pyruvate on recovery of ischemic rat heart: comparison with other oxidizable substrates. 218 87


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