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)

Glibenclamide, one of the antidiabetic sulfonylureas, is known to block ATP-dependent K+ channels. We used this drug to determine to what extent K+ loss from acutely ischemic myocardium is mediated via these channels. We also investigated whether glibenclamide would influence ischemic arrhythmias. Isolated rat hearts rendered globally ischemic showed no correlation between early lactate and K+ efflux rates. Cumulative K+ loss during 11 minutes of global ischemia (0.5 ml min-1 g-1) was reduced, from 3.2 +/- 0.3 to 2.5 +/- 0.1 mueq/g (p less than 0.025) by 1 microM glibenclamide and from 3.3 +/- 0.2 to 1.9 +/- 0.2 mueq/g (p less than 0.005) by 10 microM glibenclamide, while lactate efflux was unaltered by the drug. Glibenclamide also exhibited potent antifibrillatory activity, abolishing irreversible ventricular fibrillation during regional ischemia (0/6 vs. 5/6 controls; p less than 0.02) and during global ischemia (0/7 vs. 9/9 controls; p less than 0.01). Heart rate, coronary flow rate, peak systolic pressure, and myocardial oxygen consumption were unaltered by the drug (1 microM). Similarly, glibenclamide (1 microM) did not alter myocardial ATP, phosphocreatine or lactate content, or glucose utilization. Ventricular fibrillation threshold during normoxia was also unaltered by glibenclamide (1 microM). We conclude that K+ loss during acute myocardial ischemia is mediated partly by ATP-dependent K+ channels, and not by a tightly coupled co-efflux with anionic lactate.
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PMID:Reduction of ischemic K+ loss and arrhythmias in rat hearts. Effect of glibenclamide, a sulfonylurea. 210 70

4-(o-Benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane, CAS 90293-01-9, Celeport) has been reported to exert a protective effect on the brain against ischemic insults. However, the underlying mechanism of this action has not yet been fully elucidated. The effects of bifemelane on the intracellular pH (pHi) and energy metabolism of the ischemic brain were examined in Mongolian gerbils using in vivo 31P nuclear magnetic resonance spectroscopy. Transient global ischemia was produced by clipping both common carotid arteries for 45 min, and the brain was reperfused by releasing the clips. Bifemelane (10 or 20 mg/kg) or normal saline was administered intraperitoneally 30 min prior to the ischemia. During the ischemia, adenosine triphosphate (ATP) and phosphocreatine (PCr) were markedly reduced in association with an increase in inorganic phosphate (Pi) and decrease in pHi in both the control and bifemelane groups. The extents of energy disturbance and intracellular acidosis in the three groups were identical. After reperfusion, ATP, PCr, Pi and pHi recovered towards the pre-ischemic levels in all the groups. In the bifemelane groups, the recovery of pHi was significantly faster than in the control group. Of the two bifemelane groups, the 20 mg/kg group showed more excellent pHi recovery as compared to the 10 mg/kg group. The energy recovery in the three groups were almost identical, although the 20 mg/kg group showed some tendency towards faster recovery as compared to the control group. The present results suggest that bifemelane may accelerate recovery of the pHi after cerebral ischemia. Such an action may contribute to the cerebral protective effects of this drug against ischemic insults.
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PMID:Effect of bifemelane on the intracellular pH and energy state of the ischemic brain. 212 87

The present study was undertaken to define the effects of left ventricular hypertrophy on postischemic recovery of myocardial performance and high energy phosphate metabolism. Hemodynamics and 31P-magnetic resonance spectra were monitored simultaneously in the isolated Langendorff-perfused rat heart during 30 minutes of ischemia and 30 minutes of reperfusion. Left ventricular hypertrophy was produced by either suprarenal aortic constriction or chronic thyroxine administration. In chronic pressure overload hypertrophy, minimal coronary resistance was significantly higher (p less than 0.001) and the loss of purine nucleosides in the coronary effluent during early reperfusion significantly larger (p less than 0.001) compared with both normal hearts and thyroxine-induced hypertrophied hearts. Postischemic recovery of the baseline values for left ventricular developed pressure and phosphorylation potential was 43 +/- 4% and 82 +/- 4%, respectively, in chronic pressure overload hypertrophied hearts; 86 +/- 4% and 91 +/- 3%, respectively, in normal hearts (chronic pressure overload hypertrophy versus normal hearts, p less than 0.001 and p less than 0.05); and 100 +/- 4% and 98 +/- 2%, respectively, in thyroxine-induced hypertrophied hearts (normal hearts versus thyroxine-induced hypertrophied hearts, p less than 0.05 and p less than 0.05). Recovery after reperfusion was not related to intracellular pH, ATP, phosphocreatine, or inorganic phosphate levels during ischemia. Also, recovery was not related to developed pressure or oxygen consumption before ischemia. However, recovery was inversely related to coronary resistance and directly related to coronary flow before ischemia. Thus, functional and/or anatomic alterations of the coronary vascular bed and a greater loss of purine nucleosides during reperfusion are likely responsible for the attenuated compensatory response to ischemia and reperfusion in left ventricular hypertrophy induced by chronic pressure overload. On the other hand, the excess muscle mass per se does not seem to alter recovery, since thyroxine-induced myocardial hypertrophied hearts responded at least as well as normal hearts.
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PMID:Postischemic recovery of mechanical performance and energy metabolism in the presence of left ventricular hypertrophy. A 31P-MRS study. 213 28

Ultrastructural changes in normal and hypertrophied dog hearts under conditions of total ischemia were studied by electron microscope method. In the control group sings of irreversible damage appeared in 90 min, in the presence of phosphocreatine, 10 mM, these changes became apparent in 120 min. In the hypertrophied hearts signs of the irreversible damages became evident in 60 and 90 min in the absence and presence of phosphocreatine, respectively. Ability of phosphocreatine to protect both normal and hypertrophied myocardium allows to use it safely.
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PMID:[Ultrastructural characteristics of anti-ischemia protection of intact and hypertrophic myocardium with phosphocreatinine]. 214 81

The free radical-generating enzyme xanthine oxidase has been hypothesized to be a central mechanism of the injury which occurs in postischemic tissues; however, its importance remains controversial. Much attention has focused on the role of this enzyme in myocardial reperfusion injury. While xanthine oxidase has been observed in ischemic tissue homogenates, the presence and importance of radical generation by the enzyme in intact tissues are unknown. Therefore, we performed electron paramagnetic resonance, nuclear magnetic resonance and hemodynamic studies to measure the presence and significance of xanthine oxidase-mediated free radical generation in the isolated rat heart. When isolated perfused rat hearts were reperfused after 30 min of global ischemia, myocardial function and coronary flow were significantly improved in the presence of the definitive xanthine oxidase blocker oxypurinol. Free radical concentrations measured by spin-trapping with 5,5'-dimethyl-1-pyrroline-N-oxide were significantly decreased by oxypurinol and the energetic state of the heart was improved as reflected by an increased recovery of phosphocreatine and a higher phosphocreatine/Pi ratio. ATP recovery, however, was not altered, indicating that the improved functional and metabolic state of the heart was not due to ATP salvage. Spectrophotometric assays for the enzyme showed an increase in the amount of xanthine oxidase relative to dehydrogenase following ischemia, and a total available xanthine oxidase pool in the rat heart of approximately 150 milliunits/g of protein. Thus, xanthine oxidase is a significant source of the oxidative injury which occurs upon reperfusion of the ischemic rat heart.
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PMID:Evaluation of the role of xanthine oxidase in myocardial reperfusion injury. 215 6

Energy depletion is a primary factor initiating ischemic damage to neurons. In a separate report, we demonstrated that in vitro ischemia inhibits protein synthesis in the CA1 pyramidal neurons of the hippocampal slice via a mechanism involving extracellular calcium and N-methyl-D-aspartate (NMDA) receptor activation during the ischemic episode. In this study, we tested whether these agents accelerated the ischemic energy depletion beyond tolerable levels. ATP and phosphocreatine (PCr) were measured immediately after different durations of in vitro ischemia in the presence or absence of calcium and the NMDA receptor antagonist ketamine. The results support the contention that extracellular calcium does not contribute to the ischemic energy depletion. NMDA receptor activation accelerates the fall in ATP and PCr, but only during the first 45 s of the ischemia. Using protein synthesis inhibition as a functional indicator of ischemic damage in the hippocampal slice, we demonstrated that greater than 2 min of ischemia is necessary to inhibit protein synthesis. Thus, this threshold duration of ischemia indicates that events occurring between 2 and 5 min ischemia result in a prolonged protein synthesis inhibition.
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PMID:NMDA receptor activation accelerates ischemic energy depletion in the hippocampal slice and the demonstration of a threshold for ischemic damage to protein synthesis. 215 12

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

We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia.
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PMID:Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. 221 11

In order to test the hypothesis that the cerebral arteriovenous oxygen difference (AVDO2) and venous oxygen content (VO2) could be used to monitor brain energy metabolism in the setting of increased intracranial pressure (ICP). 12 cats were studied with 31P-magnetic resonance spectroscopy. six cats were subjected to intracranial hypertension by cisternal infusion of saline. Energy failure occurred at an average AVDO2 of 8.4 +/- 3.2 vol% (+/- standard deviation) (range 4.7 to 14.7 vol%). The VO2 at the point of metabolic failure averaged 1.45 +/- 0.6 vol% and extended over a narrower range (1.0 to 2.9 vol%). In an additional six cats, ICP was raised to the threshold of metabolic failure and hyperventilation was then instituted (pCO2 10 to 18 torr). Five of the six cats experienced a drop in VO2 with hyperventilation. In two of these animals, hyperventilation resulted in a VO2 of 1.1 vol% or less and in metabolic failure as evidenced by a fall in phosphocreatine. It is concluded that a VO2 of less than 2 vol% is correlated with brain ischemia and that the safety of hyperventilation in the setting of increased ICP can be monitored by the use of VO2.
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PMID:Cerebral venous oxygen content as a measure of brain energy metabolism with increased intracranial pressure and hyperventilation. 223 Sep 75

The development of a large animal preparation using 31P nuclear magnetic resonance (NMR) spectroscopy for the study of cerebral and myocardial metabolism during cardiopulmonary bypass (CPB) is reported. The effect of normothermic CPB on myocardial and cerebral metabolism was evaluated. Adolescent sheep were used which have low levels of 2,3-diphosphoglycerate, a compound which can interfere with the calculation of intracellular pH and inorganic phosphate content. CPB was performed using standard procedures modified for the presence of a high magnetic field and limited access to the animal. High quality 31P NMR data were obtained from the brains and hearts of these animals before and during normothermic CPB. These results demonstrate that the initiation of normothermic CPB does not change high energy phosphate levels or intracellular pH. In particular, the decreased myocardial oxygen demand associated with CPB is not associated with improvement in the levels of adenosine triphosphate or phosphocreatine. The measurements of energy metabolism and intracellular pH of the brain and heart during CPB were possible within the constraints of the NMR experiment without compromising the CPB procedure. Combining NMR and CPB techniques permits future studies of cerebral and myocardial metabolism, especially those relating to ischemia.
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PMID:The effect of cardiopulmonary bypass on brain and heart metabolism: a 31P NMR study. 223 23


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