The Effect of Combined Hypocapnia and Hypoxemia upon the Energy Metabolism of the Brain

1974 ◽  
Vol 52 (6) ◽  
pp. 1136-1146 ◽  
Author(s):  
V. MacMillan
Keyword(s):  
Energy Metabolism ◽  
Intracellular Ph ◽  
Tissue Oxygenation ◽  
Adenine Nucleotide ◽  
Energy State ◽  
Energy Charge ◽  
Tissue Levels ◽  
Hypoxic Brain ◽  
The Brain ◽  
Pyruvate Ratio

To evaluate whether hypocapnia affects the energy metabolism of the hypoxic brain, lightly anesthetized rats were maintained for 30 min at a [Formula: see text] of close to 30 mm Hg (1 mm Hg = 133 N/m2) and at [Formula: see text]'s of close to 35, 25, and 18 mm Hg, and compared with normoxic rats maintained at equivalent [Formula: see text]. The results showed that in hypoxic rats the energy state of the tissue, as evaluated from the adenylate contents and energy charge of the adenine nucleotide system, was adversely affected by exposures to [Formula: see text] of 18 mm Hg. The hypocapnia increased the accumulation of lactate during hypoxemia without altering the lactate/pyruvate ratio. Examination of the tissue levels of carbohydrate substrates, cerebral venous [Formula: see text], derived intracellular pH, and cytoplasmic NAD+/NADH ratios did not indicate that the increased tissue lactate accumulation was due to a further defect in tissue oxygenation. It is concluded that hypocapnia during hypoxemia is potentially detrimental.

scholarly journals Regulation of Extra- and Intracellular pH in the Brain in Severe Hypoglycemia

1981 ◽  
Vol 1 (1) ◽  
pp. 85-96 ◽  
Author(s):  
Dale Pelligrino ◽  
Bo K. Siesjö
Keyword(s):  
Intracellular Ph ◽  
Ph Regulation ◽  
Cell Damage ◽  
Energy State ◽  
Energy Charge ◽  
Severe Hypoglycemia ◽  
Cell Membrane Permeability ◽  
Adenylate Energy Charge ◽  
Acid Base ◽  
The Brain

Severe hypoglycemia is associated with a marked curtailment of cerebral glucose supply and with consumption of endogenous carbohydrate metabolites and amino acids, many of which exist as anions of acids. Since metabolic control of intracellular pH in acute hypo- and hypercapnia seems to be dependent on the production and consumption of metabolic acids, it must be suspected that intracellular pH in the brain is poorly regulated in hypoglycemic animals. We induced hypocapnia (Paco2 about 15 mm Hg) and hypercapnia (Paco2 about 90 mm Hg) in insulin-injected animals in “precoma” (EEG pattern of slow waves, polyspikes) and “coma” (cessation of EEG activity) and measured CSF and intracellular acid-base changes using the CO2 method. The induced hypoglycemia did not measurably alter CSF acid-base changes from the normal during hypercapnia, but it did impair CSF pH regulation in hypocapnia. Animals in precoma showed an unchanged cerebral energy state during both hypo- and hypercapnia. Regulation of intracellular pH was not measurably affected in hypercapnia but was reduced in hypocapnia. These results could be accounted for by a reduced ability of the hypoglycemic animals to produce metabolic acids in response to the decrease in Pco2, while the capacity to “consume” acids was largely retained. In comatose animals, cerebral energy state was held at normocapnic levels during hypercapnia but deteriorated during hypocapnia. In the latter condition, the reduction in adenylate energy charge correlated to a decrease in blood pressure. The capacity to alter metabolic acid levels was abolished. In spite of this, hypocapnia was associated with a marked rise in intracellular pH, in some animals to values of about 7.7 (control, 7.0), and hypercapnia caused only very moderate reduction in intracellular pH. It is proposed that the excessive increase in intracellular pH during hypocapnia was due to hypotension-induced energy failure with subsequent depolarization of cells and passive equilibration of HCO3− (or H+) across the cell membranes. In hypercapnia, the influx of HCO3− into cells was unrelated to further deterioration of cerebral energy state but could possibly have been caused by CO2-induced depolarization and/or increased cell membrane permeability to HCO3−/H+ ions. It is concluded that severe hypoglycemia disrupts intracellular pH regulation in the brain and that hypocapnia combined with moderate hypotension leads to an excessive intracellular alkalosis of potential importance for the development of cell damage.

Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia

1996 ◽  
Vol 81 (4) ◽  
pp. 1772-1777 ◽  
Author(s):  
J. C. Lamanna ◽  
M. A. Haxhiu ◽  
K. L. Kutina-Nelson ◽  
S. Pundik ◽  
B. Erokwu ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Brain Stem ◽  
Respiratory Depression ◽  
Intracellular Ph ◽  
Metabolic Changes ◽  
Nucleus Ambiguus ◽  
Electromyographic Activity ◽  
Respiratory Drive ◽  
Energy Deficiency ◽  
The Brain

LaManna, J. C., M. A. Haxhiu, K. L. Kutina-Nelson, S. Pundik, B. Erokwu, E. R. Yeh, W. D. Lust, and N. S. Cherniack.Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia. J. Appl. Physiol. 81(4): 1772–1777, 1996.—Metabolic changes in the brain stem were measured at the time when oxygen deprivation-induced respiratory depression occurred. Eucapnic ventilation with 8% oxygen in vagotomized urethan-anesthetized rats resulted in cessation of respiratory drive, monitored by recording diaphragm electromyographic activity, on average within 11 min (range 5–27 min), presumably via central depressant mechanisms. At that time, the brain stems were frozen in situ for metabolic analyses. By using 20-μm lyophilized sections from frozen-fixed brain stem, microregional analyses of ATP, phosphocreatine, lactate, and intracellular pH were made from 1) the ventral portion of the nucleus gigantocellularis and the parapyramidal nucleus; 2) the compact and ventral portions of the nucleus ambiguus; 3) midline neurons; 4) nucleus tractus solitarii; and 5) the spinal trigeminal nucleus. At the time of respiratory depression, lactate was elevated threefold in all regions. Both ATP and phosphocreatine were decreased to 50 and 25% of control, respectively. Intracellular pH was more acidic by 0.2–0.4 unit in these regions but was relatively preserved in the chemosensitive regions near the ventral and dorsal medullary surfaces. These results show that hypoxia-induced respiratory depression was accompanied by metabolic changes within brain stem regions involved in respiratory and cardiovascular control. Thus it appears that there was significant energy deficiency in the brain stem after hypoxia-induced respiratory depression had occurred.

Regulation of VO2 in red muscle: do current biochemical hypotheses fit in vivo data?

1989 ◽  
Vol 256 (4) ◽  
pp. R898-R906 ◽  
Author(s):  
R. J. Connett ◽  
C. R. Honig
Keyword(s):  
Intracellular Ph ◽  
Adenine Nucleotide ◽  
Energy State ◽  
Adenine Nucleotides ◽  
Wide Range ◽  
Glycolytic Intermediates ◽  
Red Muscle ◽  
Ph Range

Observations used to test biochemical models of the regulation of O2 consumption (VO2) by cytosolic phosphate energy state must include a change in intracellular pH and/or a change in the adenine nucleotide or phosphate pools [Connett, R. J. Analysis of metabolic control: new insights using a scaled creatine kinase model. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R949-R959, 1988]. Data were collected over a wide range of energy turnover from canine muscles in situ. Intracellular PO2, glycolytic intermediates, adenine nucleotides, creatine, phosphocreatine (PCr), phosphate, and intracellular pH were determined for each muscle. PO2 was used to eliminate muscles in which VO2 could have been O2 limited (PO2 less than 0.5 Torr). This removed an important source of heterogeneity. Because adenine nucleotide and phosphate pools were constant relative to the creatine pool, discrimination among models depended solely on pH. The observed pH range from 7.2 to 5.9 did not permit separation of [PCr] from log[( ATP4-]/[ADP3-][H2PO4-]) (phosphorylation potential) as a regulatory parameter for VO2. However, [ADP] could be eliminated as an independent regulator. Because 90% of variability in VO2 was accounted for by phosphate energetics, an independent redox component must be small when intracellular PO2 greater than 0.5 Torr.

Uremic encephalopathy: role of brain energy metabolism

1984 ◽  
Vol 247 (3) ◽  
pp. F527-F532
Author(s):  
C. A. Mahoney ◽  
P. Sarnacki ◽  
A. I. Arieff
Keyword(s):  
Renal Failure ◽  
Redox State ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
High Energy ◽  
Normal Brain ◽  
High Energy Phosphates ◽  
Adenine Nucleotide Pool ◽  
The Brain ◽  
Brain Energy

Uremia is associated with decreased brain oxygen consumption in humans and with decreased brain energy consumption in rodent models of acute renal failure. We measured the levels of high-energy phosphates and glycolytic intermediates in the brain of dogs with acute or chronic renal failure. We used methods of rapid brain tissue fixation that trap these labile metabolites at their in vivo levels. Creatine phosphate, ATP, and glucose were normal in the brain of animals with renal failure, indicating a normal brain energy reserve. The brain energy charge, which is the fraction of the total adenine nucleotide pool that contains high-energy phosphates, (ATP + 1/2ADP)/(ATP + ADP + AMP), was also normal despite an 8% decrease in the total adenine nucleotide pool. Mild hypoxia failed to alter the level of any of these metabolites. The brain redox state, (NAD+)/(NADH), was normal to high in acute renal failure, suggesting that oxygen supply was not limiting oxygen consumption. In the face of normal brain energy reserves, energy charge, and redox state, the decreased energy consumption of uremic brain probably results from decreased demand rather than limited supply.

scholarly journals REPRODUCTIVE SENESCENCE IMPAIRS THE ENERGY METABOLISM OF HUMAN GRANULOSA CELLS

2021 ◽  
Author(s):  
Gustavo Nardini Cecchino ◽  
Juan A. García-Velasco ◽  
Eduardo Rial
Keyword(s):  
Energy Metabolism ◽  
Granulosa Cells ◽  
Adenine Nucleotide ◽  
Aerobic Glycolysis ◽  
Energy Charge ◽  
Cumulus Cells ◽  
Control Group ◽  
Reproductive Senescence ◽  
Age Related

AbstractFemale age is the single greatest factor influencing reproductive performance. It is widely known that mitochondrial dysfunction plays a key role in reproductive senescence. Ovarian bioenergetics includes a sophisticated metabolic synergism between oocytes and human mural granulosa cells (GCs), which is crucial for oocyte maturation during follicular growth. These cells are believed to be potential biomarkers of oocyte quality. It has been proposed that alterations in their energy metabolism could lead to infertility. We investigated if there is an age-related effect on the energy metabolism of human mural granulosa cells. We performed an observational prospective cohort and experimental study including 127 women that underwent in vitro fertilization cycles allocated to two groups: a control group comprising oocyte donors aged less than 35 years and a group of infertile women aged over 38 years. The bioenergetics of cumulus cells and purified mural GCs were determined from oxidative phosphorylation parameters, aerobic glycolysis and adenine nucleotide levels. We have found that human mural GCs and cumulus cells present a high glycolytic profile and that the follicular fluid is critical to sustain their energy metabolism. GCs from older women present lower mitochondrial respiration and glycolysis than those from young donors which is not accompanied by a lower respiratory capacity. The diminished energy metabolism leads to a decrease in the total cellular energy charge. We conclude that, as women age, mural granulosa cells exhibit a reduction in their energy metabolism that is likely to influence female reproductive potential.

Hepatic preconditioning preserves energy metabolism during sustained ischemia

2000 ◽  
Vol 279 (1) ◽  
pp. G163-G171 ◽  
Author(s):  
C. Peralta ◽  
R. Bartrons ◽  
L. Riera ◽  
A. Manzano ◽  
C. Xaus ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
High Energy ◽  
Energetic Cost ◽  
Main Role ◽  
Adenylate Energy Charge ◽  
Glycogen Depletion ◽  
Adenine Nucleotide Pool

We evaluated the possibility that ischemic preconditioning could modify hepatic energy metabolism during ischemia. Accordingly, high-energy nucleotides and their degradation products, glycogen and glycolytic intermediates and regulatory metabolites, were compared between preconditioned and nonpreconditioned livers. Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and adenylate energy charge; the accumulation of adenine nucleosides and bases was much lower in preconditioned livers, thus reflecting slower adenine nucleotide degradation. These effects were associated with a decrease in glycogen depletion and reduced accumulation of hexose 6-phosphates and lactate. 6-Phosphofructo-2-kinase decreased in both groups, reducing the availability of fructose-2,6-bisphosphate. Preconditioning sustained metabolite concentration at higher levels although this was not correlated with an increased glycolytic rate, suggesting that adenine nucleotides and cAMP may play the main role in the modulation of glycolytic pathway. Preconditioning attenuated the rise in cAMP and limited the accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen depletion. Our results suggest the induction of metabolic arrest and/or associated metabolic downregulation as energetic cost-saving mechanisms that could be induced by preconditioning.

scholarly journals Hypoxia and the energy charge of the cerebral adenylate pool

1972 ◽  
Vol 127 (2) ◽  
pp. 351-355 ◽  
Author(s):  
J. W. Ridge
Keyword(s):  
Rat Brain ◽  
Feedback Inhibition ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Nucleotide Synthesis ◽  
Limited Ability ◽  
Adenylate Pool ◽  
The Brain

A brief period of anoxia in vivo causes a transitory decrease in the size of the adenylate pool in the rat brain. This is probably caused by feedback inhibition by AMP of adenine nucleotide synthesis. Exposing rats to various degrees of hypoxia suggests that the sensitivity of the brain to lack of O2 results from the brain's limited ability to maintain an adequate energy charge in unfavourable circumstances.

The influence of inhibiting no formation on metabolic recovery of ischemic rat heart by apelin-12

2012 ◽  
Vol 58 (6) ◽  
pp. 702-711 ◽  
Author(s):  
O.I. Pisarenko ◽  
Yu.A. Pelogeykina ◽  
V.S. Shulzhenko ◽  
I.M. Studneva ◽  
Z.D. Bespalova ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cardiac Function ◽  
Solid Phase ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Phase Method ◽  
No Formation ◽  
Rat Hearts ◽  
Solid Phase Method ◽  
Adenine Nucleotide Pool

Apelin 12 (A-12) was synthesized by the automatic solid phase method with use of Fmoc 1H-NMR spectroscopy and mass spectrometry. Effects of apelin-12 (a peptide comprised of 12 aminoacids, A-12) on recovery of energy metabolism and cardiac function were studied in isolated working rat hearts perfused with Krebs buffer (KB) containing 11 mM glucose that were subjected to global ischemia and reperfusion. A short-term infusion of μM 140 A-12 in KB prior to ischemia enhanced myocardial ATP, the total adenine nucleotide pool (ΣAN=ATP+ADP+AMP) and the energy charge of cardiomyocites ((ATP+0.5ADP)/ΣAN) at the end of reperfusion compared with control (KB infusion) and reduced lactate content and lactate/pyruvate ratio in reperfused myocardium to the initial values. This effect was accompanied by improved recovery of coronary flow and cardiac function. Coadministration of 140 μM A-12 and 100 μM L-NAME (the nonspecific NOS inhibitor) profoundly attenuated the peptide influence on metabolic and functional recovery of reperfused hearts. The results indicate involvement of NO, formed under the peptide action, in mechanisms of cardioprotection that are tightly associated with recovery of energy metabolism in postischemic heart.

ATP consumption by uncoupled mitochondria activates sarcolemmal KATP channels in cardiac myocytes

2001 ◽  
Vol 280 (4) ◽  
pp. H1882-H1888 ◽  
Author(s):  
Norihito Sasaki ◽  
Toshiaki Sato ◽  
Eduardo Marbán ◽  
Brian O'Rourke
Keyword(s):  
Creatine Kinase ◽  
Kinase Inhibitor ◽  
Atp Hydrolysis ◽  
Adenine Nucleotide ◽  
Energy State ◽  
Energy Charge ◽  
Partial Recovery ◽  
Rapid Rise ◽  
Atpase Inhibitor ◽  
Slow Increase

We tested whether close coupling exists between mitochondria and sarcolemma by monitoring whole cell ATP-sensitive K+ (KATP) current ( I K,ATP) as an index of subsarcolemmal energy state during mitochondrial perturbation. In rabbit ventricular myocytes, either pinacidil or the mitochondrial uncoupler dinitrophenol (DNP), which rapidly switches mitochondria from net ATP synthesis to net ATP hydrolysis, had little immediate effect on I K,ATP. In contrast, in the presence of pinacidil, exposure to 100 μM DNP rapidly activated I K,ATP with complex kinetics consisting of a quick rise [time constant of I K,ATP increase (τ) = 0.13 ± 0.01 min], an early partial recovery (τ = 0.43 ± 0.04 min), and then a more gradual increase. This DNP-induced activation of I K,ATP was reversible and accompanied by mitochondrial flavoprotein oxidation. The F1F0-ATPase inhibitor oligomycin abolished the DNP-induced activation of I K,ATP. The initial rapid rise in I K,ATP was blunted by atractyloside (an adenine nucleotide translocator inhibitor), leaving only a slow increase (τ = 0.66 ± 0.17 min, P < 0.01). 2,4-Dinitrofluorobenzene (a creatine kinase inhibitor) slowed both the rapid rise (τ = 0.20 ± 0.01 min, P < 0.05) and the subsequent declining phase (τ = 0.88 ± 0.19 min, P < 0.05). From single KATP channel recordings, we excluded a direct effect of DNP on KATP channels. Taken together, these results indicate that rapid changes in F1F0-ATPase function dramatically alter subsarcolemmal energy charge, as reported by pinacidil-primed KATP channel activity, revealing cross-talk between mitochondria and sarcolemma. The effects of mitochondrial ATP hydrolysis on sarcolemmal KATP channels can be rationalized by reversal of F1F0-ATPase and the facilitation of coupling by the creatine kinase system.

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