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)

In order to investigate the role of Na+,K(+)-ATPase in the development of neuronal necrosis following cerebral ischemia, ischemia was induced in gerbils by occluding the common carotid artery unilaterally for 10 min. A time-course analysis revealed that significant reductions of the Na+,K(+)-ATPase activity in the cerebral cortex and hippocampus were manifested at 15 min, 30 min, and 1 h, and returned to the control level one day following recirculation. No apparent alterations of the Mg(2+)-ATPase activity, on the other hand, were obtained throughout the experimental period. Furthermore, Scatchard analyses of [3H]ouabain binding to the cerebral cortex membranes disclosed that the Bmax values invariably decreased without any change of Kd values following ischemia. It has also been shown that treatment of the animals with an agent known to mitigate ischemic neuronal necrosis, i.e. BY-1949, significantly reversed such derangements. These results suggest that the recovery of decreased Na+,K(+)-ATPase activity shortly after ischemia exerts a protective effect against ischemic brain damage.
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PMID:Neurochemical correlates of selective neuronal loss following cerebral ischemia: role of decreased Na+,K(+)-ATPase activity. 153 68

The purpose of this study was to investigate the energy movement of the normothermic ischemic liver. Liver ischemia was induced in normal and cirrhotic rats, by cross-clamping portal vein and hepatic artery, bypassing the portal blood to the jugular vein through a shunt tube. The levels of ATP of the hepatic tissue was measured before and after hepatic ischemia, by HPLC and 31P-NMR. Before hepatic ischemia, the levels of ATP was greater in normal liver than in cirrhotic liver, but after ischemia it was significantly smaller in normal liver than cirrhotic liver. Generally they say that the greater is the ATP of the tissue, the greater is the viability of the tissue. But this experiment showed the contrary. Cirrhotic liver can't use glucose sufficiently, therefore acetyl-CoA, which is used in TCA-cycle, is derived from the resolution of fatty acid. As a result, free fatty acid and acyl-CoA increase in cirrhotic liver, and suppress Na(+)-K(+)-ATPase. I conclude that the cirrhotic liver can't effectively use ATP to maintain the potential of the liver cells, maybe, because of it's abnormal metabolism of glucose. Therefore, the levels of ATP was greater in cirrhotic liver than in normal liver after hepatic ischemia.
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PMID:[Investigation of hepatic energy metabolism in normothermic hepatic ischemia--comparison between normal and cirrhotic rat liver]. 154 96

Changes in content of brain mitochondrial phospholipids were examined in rats after 30 and 60 min of decapitation ischemia compared with controls, to explore the degradation of the mitochondrial membrane and its relation to dysfunction of mitochondria. Activities of respiratory functions and respiratory enzymes (cytochrome c oxidase; F0F1-ATPase) decreased significantly during ischemia. Considerable decreases in cardiolipin and phosphatidylinositol content were observed after 60 min, and other phospholipids showed similar but nonsignificant decreases in content. The amount of polyunsaturated fatty acids chains, such as arachidonic and docosahexaenoic acids, was reduced in each phospholipid, in some cases significantly, after 30 and 60 min of ischemia in time-dependent manners. Degradation of mitochondrial phospholipids during ischemia associated with the deterioration of mitochondrial respiratory functions suggested the significance of such changes in phospholipid content in disintegration of cellular energy metabolism during cerebral ischemia.
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PMID:Degradation of mitochondrial phospholipids during experimental cerebral ischemia in rats. 165 Mar 95

The delayed effects of 7-oxo-prostacyclin, protecting the heart against extrasystoles, ventricular fibrillation, and cardiac arrest induced by high doses of ouabain or in ischemia and postischemic reperfusion, have already been described; but little is known about the molecular mechanisms involved. In this study, 50 micrograms.kg-1 7-oxo-prostacyclin administered intramuscularly significantly stimulated the activity of (Na+K+)-ATPase in rat heart sarcolemma 24 and 48 hours after application (p less than 0.01 and p less than 0.001, respectively). Kinetic analysis revealed a mixed type of stimulation of ATPase activity, with increased Vmax and decreased Km values. Cycloheximide (1 mg.kg-1) applied together with 7-oxo-prostacyclin, significantly antagonized the stimulatory effect of 7-oxo-prostacyclin, and had a modulatory effect on the kinetics of the (Na+K+)-ATPase both 24 and 48 hours after administration. The results show that protein synthesis is involved in the mechanism of the increase in enzyme activity.
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PMID:Increased activity of sarcolemmal (Na+K+)-ATPase is involved in the late cardioprotective action of 7-oxo-prostacyclin. 165 98

Lysophosphatidylcholine (LPC) accumulates in myocardial tissues during ischemia, and has toxic effects which may contribute to the arrhythmias and relaxation abnormalities that occur during acute ischemia. These effects of LPC may be mediated in part by calcium overload. To test this hypothesis, spontaneously contracting cultured embryonic chick ventricular myocytes were superfused with various concentrations of LPC (10, 50 and 100 microM) while effects on contractile motion (video motion detector) and changes in free intracellular calcium ion concentration ([Ca2+]i indo-1 fluorescence) were determined. At concentrations greater than or equal to 10 microM, a dose-related, time-dependent effect occurred after exposure to LPC, consisting of the development of contracture and marked elevation of [Ca2+]i. LPC also produced a dose-related, time-dependent inhibition of K+ uptake, indicating there was inhibition of the Na(+)-K+ ATPase Na+ pump. However, the LPC-induced increase in [Ca2+]i was not due to Na+ overload caused by inhibition of the Na(+)-K+ ATPase Na+ pump because superfusion with a zero-Na+ solution did not prevent an increase in [Ca2+]i after LPC exposure; and the increase in [Ca2+]i after exposure to LPC occurred too rapidly to be accounted for by Na+ pump inhibition. Removal of extracellular Ca2+ prevented the rise in [Ca2+]i, after exposure to LPC but treatment with verapamil failed to inhibit the increase in [Ca2+]i induced by LPC. We conclude that LPC produces contracture due to an increase [Ca2+]i. These effects are seen at concentrations of 10 microM and greater, are not due to altered Na(+)-K+ ATPase Na+ pump or calcium channel function, and are probably related to the detergent properties of this amphiphile. There effects may account in part for myocardial dysfunction during ischemia in intact tissue.
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PMID:Lysophosphatidylcholine increases cytosolic calcium in ventricular myocytes by direct action on the sarcolemma. 165 42

In order to understand the pathophysiology of myocardial stunning, reversibility, accumulation and continuity of ischemic myocardial damage after reperfusion should be studied. Then, to analyze these three factors, myocardial function, metabolism and morphology under ischemia and reperfusion were studied in anesthetized, open-chest dogs. When myocardial ischemia was induced by occlusion of the left anterior descending coronary artery, percentage regional systolic shortening (%SS) of ischemic myocardium sharply decreased and became stable 10 min after occlusion. After reperfusion, ischemic myocardium showed active shortening after within 30-min occlusion, but did not after more than 60-min occlusion. During 90-min of ischemia, extracellular K+ concentration (Ke) steeply increased for first 10 min and was almost stable for next 10 min. Then, Ke straightly increased till 90 min. Metabolic rates, calculated from myocardial tissue CO2 and pH, steeply increased for first 20 min and sharply decreased for next 10 min. After 30 min, these two variables were almost stable, near zero. By electron-microscopy with cytochemistry, distribution of Na/K ATPase to myocardial cell membrane was observed to be almost after 15-min occlusion but distinctly sparse with destruction of cell membrane after 30-min occlusion. Therefore, irreversible myocardial damage appears after about 20-min ischemia and is almost complete after 60 min. Reversibility of damage to ischemic myocardium after reperfusion may mainly occur within 60-min ischemia. Although stunned myocardium in a narrow sense is may appear after reperfusion within less than 20-min of ischemia, stunned myocardium in a broad sense may appear within less than 60-min ischemia. When reversible myocardial ischemia (4- or 15-min occlusion) was repeated after short time intervals (20-min reperfusion), %SS of ischemic myocardium was gradually decreased with each ischemic episode. Active shortening of ischemic myocardium disappeared after more than two episodes of 15-min occlusion. Fluctuation of PCO2, pH and Ke of ischemic myocardium was gradually depressed with each occlusion. Metabolic viability of ischemic myocardium was cumulatively depressed by repeated brief occlusion. Naturally, myocardial damage was more severe after repeated 15-min occlusion than after 4-min occlusion. Accumulation of ischemic myocardial damage may arise as brief ischemia, which only induces reversible damage, is repeated. At last, continuity of ischemic myocardial damage was studied. The effect of 5-min occlusion to %SS of ischemic myocardium was apparently reversed after 90-min reperfusion. Early contractile failure was advanced even after very short duration of ischemia. Thus, myocardial function will be latently damaged.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pathophysiology of myocardial stunning: reversibility, accumulation and continuity of the ischemic myocardial damage after reperfusion. 165 10

This study was undertaken to compare the effect of low to normal serum calcium on biochemical parameters in the myocardium of dogs subjected to 90 min of coronary artery ligation followed by 30 min reperfusion. The accumulation of calcium, the decrease of adenosine triphosphate (ATP) and creatine phosphate (CP) and the inhibition of sarcolemmal ouabain-sensitive Na+/K(+)-ATPase which are prominent findings in the ischemic-reperfused myocardium, were studied under normal and low serum Ca produced by normal and modified hemodialysis (HD). The results showed a lower accumulation of Ca (P less than 0.002) in the ligated-reperfused myocardium of dogs subjected to low-calcium HD. In the same group of animals ATP was protected to some extent while CP was completely preserved. This may indicate that during reperfusion with low Ca, restored ATP is further utilized for CP regeneration. The activity of Na+/K(+)-ATPase was within normal values in the ligated-reperfused myocardium of the low-calcium group. The significantly (P less than 0.001) negative correlation between tissue calcium concentration and Na+/K(+)-ATPase activity under various conditions examined, provided additional evidence that low calcium is a protective factor of the enzyme activity during ischemia and reperfusion.
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PMID:Effect of low calcium on high-energy phosphates and sarcolemmal Na+/K(+)-ATPase in the infarcted-reperfused heart. 166 37

Isolated working rat hearts were exposed to 25 min ischemia, and functional recovery was assessed by aortic flow (AoF) and rate-pressure product (RPP) to evaluate the beneficial effects of potassium (20 mM) induced arrest (K-arrest) prior to ischemia. K-arrest improved the recovery of function after 30 min of reperfusion compared with the control group (%AoF: 68 +/- 6 vs 0%, %RPP: 90 +/- 3% vs 60 +/- 3%, p less than 0.01). The accumulation of Ca++ at the end of reperfusion was less in hearts with K-arrest (2.2 +/- 0.1 vs 4.5 +/- 0.3 mumol/g dry, p less than 0.01). There was no difference between the two groups in high energy phosphate content at the end of ischemia. The increase in intracellular Na+ (Nai) during ischemia was reduced in hearts with K-arrest (delta: 19 vs 46 mumol/g dry), and the level of intracellular K+ (Ki) was higher at the end of ischemia in hearts with K-arrest (341 +/- 4 vs 318 +/- 2 mumol/g dry, p less than 0.01). During the first 5 min of reperfusion, the level of Ki in K-arrested hearts jumped to a higher level than in the control group (delta: 15 vs 2 mumol/g dry, p less than 0.01). The level of Nai was lower in hearts with K-arrest after 5 min of reperfusion. These data suggested that K-arrest might preserve the activity of Na+/K+ ATPase during ischemia and early reperfusion, and that it attenuated the increase in Nai during ischemia and reperfusion, which resulted in less Ca++ overload during reperfusion via the Na+/Ca++ exchange mechanism and led to improved recovery.
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PMID:[Mechanism of myocardial protection with potassium arrest in isolated ischemic rat hearts]. 166 47

Acute myocardial ischemia and reperfusion in rats increased glutamic oxalacetic transaminase (GOT), non-esterified fatty acid (FFA), malondialdehyde (MDA) content. Furyl-dihydropyridines I 10 mg.kg-1 decreased the release of GOT, FFA, MDA of ischemic myocardium, and prevent ischemia-reperfusion arrhythmia. Furyl-dihydropyridines I increased Na, K-ATPase activity and N-acethylneuraminic acid (NANA) content of erythrocyte membranes, inhibited Ca-ATPase activity of erythrocyte membranes in rats. The results suggested that the mechanism of protecting the ischemic-reperfused myocardium might be associated with the inhibition of cellular lipid peroxidation and Ca-ATPase activity of cell membranes.
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PMID:[Effects of furyl-dihydropyridines I on lipid peroxides of ischemic myocardium and ATPases activity of erythrocyte membranes in rats]. 166 69

Direct and indirect evidence suggests that Na+/K(+)-ATPase activity is reduced or insufficient to maintain ionic balances during and immediately after episodes of ischemia, hypoglycemia, epilepsy, and after administration of excitotoxins (glutamate agonists). Recent results show that inhibition of this enzyme results in neuronal death, and thus a hypothesis is proposed that a reduction and/or inhibition of this enzyme contributes to producing the central neuropathy found in the above disorders, and identifies potential mechanisms involved. While the extent of inhibition of Na+/K(+)-ATPase during ischemia, hypoglycemia and epilepsy may be insufficient to cause neuronal death by itself, unless the inhibition is severe and prolonged, there are a number of interactions which can lead to a potentiation of the neurotoxic actions of glutamate, a prime candidate for causing part of the damage following trauma. Presynaptically, inhibition of the Na+/K(+)-ATPase destroys the sodium gradient which drives the uptake of acidic amino acids and a number of other neurotransmitters. This results in both a block of reuptake and a stimulation of the release not only of glutamate but also of other neurotransmitters which modulate the neurotoxicity of glutamate. An exocytotic release of glutamate can also occur as inhibition of the enzyme causes depolarization of the membrane, but exocytosis is only possible when ATP levels are sufficiently high. Postsynaptically, the depolarization could alleviate the magnesium block of NMDA receptors, a major mechanism for glutamate-induced neurotoxicity, while massive depolarization results in seizure activity. With less severe inhibition, the retention of sodium results in osmotic swelling and possible cellular lysis. A build-up of intracellular calcium also occurs via voltage-gated calcium channels following depolarization and as a consequence of a failure of the sodium-calcium exchange system, maintained by the sodium gradient.
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PMID:Inhibition of sodium-potassium-ATPase: a potentially ubiquitous mechanism contributing to central nervous system neuropathology. 166 97


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