Perturbation of cellular energy state in complete ischemia: Relationship to dissipative ion fluxes

Ekholm, Anders; Asplund, Barbro; Siesjö, Bo K.

doi:10.1007/bf00229255

Cited by 35 publications

(14 citation statements)

References 38 publications

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“…This may be produced in part by an increase in K + conductance and may be related to a decrease in the ATP/adenosine diphosphate ratio. [2] This is consistent with radiological studies showing that ischemia is associated with decreases in local neuronal metabolism. [7] CONCLUSIONS Studies suggest that enhanced neuronal damage is produced by ischemia when lactate approaches 18 to 20 µmol/g.…”

Section: Acidosis In Relation To Other Parameterssupporting

confidence: 87%

Brain tissue acid-base changes during ischemia

Hoffman¹,

Charbel²,

Edelman³

et al. 1997

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It is likely that brain tissue acidosis during ischemia is associated with neuronal injury. The authors measured brain extracellular H+, PCO2 and HCO3- concentrations during an ischemic event produced by temporary occlusion of the middle or anterior cerebral arterial distributions, with a 10-minute recovery period. Patients who were to undergo craniotomy for cerebrovascular surgery were recruited for the study. A probe that measures PCO2, pH, and temperature was inserted into tissue at risk for ischemia during temporary arterial occlusion. As a control for this treatment, PaCO2 was increased 10 mm Hg in five patients over a 10-minute period. Under baseline conditions, there was no difference in arterial blood pressure, blood gas levels, or brain temperature between patients who underwent temporary arterial occlusion or those in whom hypercapnia was induced. In patients in whom hypercapnia was induced, H+, PCO2, and HCO3- concentrations increased and all values returned to baseline levels within 10 minutes. In 10 patients who underwent a median 9-minute arterial occlusion, transient ischemia was seen with an increase in tissue H+ and PCO2 levels of 100% and 60%, respectively, and a 20% decrease in HCO3-levels. After a 10-minute postischemic recovery, only PCO2 had returned to baseline levels. These results are consistent with a rapid equilibration of lactic acidosis across the cell membrane during ischemia which decreases HCO3- concentration. After ischemia, extracellular acidosis may be prolonged because of the extrusion of H+ from the cell by membrane ion exchange.

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Section: Acidosis In Relation To Other Parameterssupporting

confidence: 87%

Brain tissue acid-base changes during ischemia

Hoffman¹,

Charbel²,

Edelman³

et al. 1997

FOC

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“…During ischemia, additional P i is accumulated when ATP and other nucleotide triphosphates are hydrolysed, and when accumulation of AMP leads to further hydrolysis of AMP to adenosine and P i (Ekholm et al, 1992;Folbergrová et al, 1990). After long periods of ischemia, when purine and pyrimidine nucleotides are extensively degraded, the P i pool may increase to 5-10 mM or above.…”

Section: Discussionmentioning

confidence: 99%

Acidosis Promotes the Permeability Transition in Energized Mitochondria: Implications for Reperfusion Injury

Kristián

Bernardi

Siesjö

2001

Journal of Neurotrauma

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We have studied the influence of pH on opening of the mitochondrial permeability transition pore (PTP) in both deenergized and energized mitochondria in the presence of Pi. In deenergized mitochondria from rat brain and heart, we observed the expected inhibition of Ca2+-induced PTP opening at increasingly acidic pH values. Unexpectedly, mitochondria energized with either electron transport complex I or complex II substrates displayed the opposite behavior, acidic pH promoting rather than inhibiting PTP opening. We show that the potentiating effect of acidic pH is due to an increased rate of Pi uptake. The data also revealed that brain mitochondria are more heterogeneous than heart or liver mitochondria in relation to onset of a permeability transition, and that this heterogeneity depends on their Pi transport capacity. Taken together, these results indicate that the inhibitory effects of acidic pH on the PTP may be overcome in situ by an increased rate of Pi uptake, and that ischemic and postischemic acidosis may worsen rather than relieve PTP-dependent tissue damage.

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“…At the same time, though, and as a result of accumulation s f ABPf, AMPf, and Pi, glycolysis is stimulated, and lactate-plus H+ accumulate, leading to a reduction of pHi and pH,. Depolarization occurs after 40 -45 s. At that time, tissue lactate content has increased to about 6 mmol -kg-', (1990) and Ekholm et al (1991aEkholm et al ( , 1992 i.e., to about half the final value reached in ischemia in normoglycernic animals.…”

Section: Coupling Of Cellular Energy Rnetabo8ism and Acid-base Changementioning

confidence: 94%

Coupling among changes in energy metabolism, acid-base homeostasis, and ion fluxes in ischemia

Katsura

Ekholm²,

Siesjö³

1992

Can. J. Physiol. Pharmacol.

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This article attempts correlating changes in cellular energy metabolism, acid-base alterations, and ion homeostasis in ischemia and other conditions. It is emphasized that loss of ion homeostasis, with thermodynamically downhill fluxes of K+, Ca2+, Na+, Cl-, and H+, occurs because energy production fails and (or) ion conductances are increased. In ischemia, energy failure is the leading event but, in hypoglycemia, activation of ion conductances is what precipitates energy failure. The initial event is a rise in K+ e, at least in part caused by activation of K+ conductances modulated by Ca2+ or ATP/ADP ratio. Secondarily, this leads to release of excitatory amino acids and massive activation of unspecific cation (and anion) conductances. Production of H+ occurs in states characterized by energy failure (ischemia and hypoxia) or by alkalosis (hypocapnia and ammonia accumulation). H+ equilibrates between intra- and extra-cellular fluid via nonionic diffusion of lactic acid, and transmembrane fluxes of H+ or HCO3- via ion channels. Since the relationship between lactate and either pHi or pHe is linear, there are no abrupt pH shifts explaining why hyperglycemia worsens ischemic damage. The reversible insults seem to induce a sustained stimulation of H+ extrusion from cells giving rise to intracellular alkalosis and extracellular acidosis.

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Perturbation of cellular energy state in complete ischemia: Relationship to dissipative ion fluxes

Cited by 35 publications

References 38 publications

Brain tissue acid-base changes during ischemia

Brain tissue acid-base changes during ischemia

Acidosis Promotes the Permeability Transition in Energized Mitochondria: Implications for Reperfusion Injury

Coupling among changes in energy metabolism, acid-base homeostasis, and ion fluxes in ischemia

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