Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interconnections between EEG, intermediary and energy metabolism of the brain cortex and CSF potassium level are studied during severe hypercapnia in anaesthetized, artificially ventilated cats. Hypercapnic animals were ventilated with 40 to 50% to CO2 in oxygen. During severe hypercapnia the EEG becomes isoelectric. The CSF potassium concentration is raised and the changes in metabolism suggest an acidosis-induced inhibition of phosphofructokinase and, probably, of hexokinase. The energy charge potential remains unchanged whereas the cortical ATP concentration increases slightly. It is assumed that the changes in P-creatine and creatine levels are related to the pH-dependency of creatine phosphokinase. Recovery animals were ventilated with 40% CO2 in O2 and subsequently with room air. After termination of CO2 inhalation the EEG reappears, the CSF potassium concentration normalizes, and the inhibition of the glycolytic enzymes disappears. The energy charge potential shows a small decrease. It is not possible to trace back the disappearance of the EEG to only one of the recorded parameters. Cortical P-creatine levels, CSF potassium concentration, changes in membrane permeability and cortical amino acid concentrations are considered in this context.
 ...
PMID:Influence of severe hypercapnia upon cerebral cortical metabolism, CSF electrolyte concentrations and EEG in the cat. 13 59

Systemic and cerebral metabolic responses to acute anoxia were studied in term-fetal and neonatal rats in order to account for the greater anoxic tolerance of fetuses. Measurements of blood acid-base balance were correlated with changes in the concentrations of adenine nucleotides, creatine, phosphocreatine, and glycogen in brain, and of glucose, pyruvate, and lactate in brain, blood, and cerebrospinal fluid during 1) exposure (20-40 min) to 100% nitrogen at 37 degrees C, and 2) subsequent recovery in air. Blood PCO2 was higher initially in fetuses and increased more rapidly during anoxia in fetuses than in neonates, exceeding 150 mmHg after 20 min. Brain glycogen, phosphocreatine, and total adenine nucleotides declined more slowly in fetuses than in neonates during anoxia, whereas brain glucose levels declined at similar rates in the two groups. From the changes in these preformed and potential energy stores, it was estimated that total cerebral energy consumption during anoxia was significantly lower in fetuses. The data suggest that the more severe hypercapnia superimposed on anoxia in fetuses decreased cerebral metabolic demands, and thus prolonged survival. An incidental finding was that L-lactate readily enters the immature brain from the blood during anoxia, and in the early recovery phase may constitute the preferred substrate for cerebral oxidative metabolism, sparing glucose.
 ...
PMID:Carbohydrate metabolism in fetal and neonatal rat brain during anoxia and recovery. 127 68

Metabolic tolerance of low intracellular pH (pH(i)) was studied in well-oxygenated, perfused, neonatal, rat cerebrocortical brain slices (350 microns thick) by inducing severe hypercapnia. In each of 17 separate experiments 80 brain slices (approximately 3.2 g wet weight) were suspended in an NMR tube, perfused with artificial CSF (ACSF), and studied at 4.7 T with 31P and 1H NMR spectroscopy. Spectra obtained every 5 min monitored relative concentrations of lactate or high-energy phosphate metabolites, from which pH(i) and extracellular pH were determined. Unperturbed slice preparations were metabolically stable for > 10 h, with no significant changes occurring in pHi, ATP, phosphocreatine (PCr), inorganic phosphate, or lactate. Different levels of hypercapnia were produced by sequentially perfusing slices with the following different ACSF batches, each having previously been equilibrated with a specific mixture of CO2 in oxygen: (a) 10% CO2, 15 min of perfusion; (b) 30% CO2, 15 min of perfusion; (c) 50% CO2, 15 min of perfusion; (d) 70% CO2, 30 min of perfusion; (e) 50% CO2, 15 min of perfusion; (f) 30% CO2, 15 min of perfusion; and (g) 10% CO2, 15 min of perfusion. At the completion of this protocol slices were again perfused with fresh ACSF that was equilibrated with a 95% O2/5% CO2 gas mixture. In each of five separate 1H and 31P experiments, brain slices were recovered within 2 h after termination of exposure to high CO2. The pHi was determined from measurements of the chemical shift difference between phosphoethanolamine and PCr, using a calibration curve obtained for our preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tolerance of low intracellular pH during hypercapnia by rat cortical brain slices: A 31P/1H NMR study. 140 24

Endurance muscle performance is highly dependent on ATP production from mitochondrial oxidative phosphorylation. To study the role of the mitochondrial oxidative enzymes in muscle fatigue, we analyzed the relationship between the concentrations of substrates associated with ATP synthesis and the muscle performance of electrically stimulated rabbit muscle under CO2-induced acidosis. Two different conditions of pacing-induced muscle performance were produced in the gastrocnemius and soleus muscle groups in anesthetized rabbits by stimulating the sciatic nerve submaximally at two frequencies. Phosphorus nuclear magnetic resonance was used to measure ATP, phosphocreatine, and Pi and to provide data for a calculation of intracellular pH and free ADP. To induce acidosis, the animal was ventilated with 20% CO2. The administration of CO2 effectively reduced the intracellular pH from 6.9 to 6.7 and reduced the isometric tension-time integral (TTI) to below half the value measured in normocapnia at the low pacing frequency. A twofold increase in the pacing frequency resulted in a doubling of the TTI in normocapnia and a tripling of TTI in hypercapnia. The increases in TTI corresponded with increases in free ADP and Pi concentrations. Under the various conditions, all free ADP values were near the in vitro Michaelis-Menten constant (Km) of ADP. The Michaelis-Menten relationship of the oxidative phosphorylative enzymes was applied to the change in substrate concentrations with respect to TTI. From this relationship we observed that the in vivo Km of free ADP was 26 microM, which is close to the in nitro Km, and that Km and maximal reaction velocity did not change under hypercapnia and increased pacing frequency.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Substrate regulation of mitochondrial oxidative phosphorylation in hypercapnic rabbit muscle. 155 27

NMR in vivo spectroscopy is one of the few methods available for non-invasive investigations of cerebral metabolism in animals and humans. 31P and 1H spectroscopy are particularly suitable for monitoring the cerebral energy metabolism by determining the cerebral levels of ATP, ADP, phosphocreatine (PCr), inorganic phosphate (Pi), lactate and intracellular pH (pHi). These techniques also seem to be suitable for studying the effects of anesthetics by directly comparing the anesthetized and unanesthetized states in the same subject. The effects of halothane and isoflurane on the changes elicited in the cerebral energy metabolism by experimental hypercapnia were investigated by in vivo NMR spectroscopy. Halothane was found to aggravate the decrease in PCr attributed to the shift in creatine kinase equilibrium induced by the cerebral acidosis associated to hypercapnia, while the level of cerebral ADP was decreased to a lesser extent than in unanesthetized animals. In contrast isoflurane did not modify the changes in cerebral energy metabolism elicited by hypercapnia except that the decrease in PCr was significantly slowed, suggesting a lower creatine kinase activity. These data indicate that isoflurane and halothane act by two different mechanisms to produce a decrease in oxygen consumption. Halothane could interfere with oxidative metabolism by disturbing ATP metabolism, while isoflurane could decrease oxygen consumption by a general sedative action, slowing both cerebral functional activity and cerebral energy homeostasis.
 ...
PMID:[Value of in vivo NMR spectroscopy in the study of cerebral metabolism under inhalation anesthesia]. 184 37

Phosphocreatine (PCr) and intracellular pH changes were monitored by 31P-NMR spectroscopy in isolated, arterially perfused cat biceps and soleus muscles, while the pH of the CO2-bicarbonate buffered perfusate was decreased from 7.1-7.4 to 6.4-6.7 by increasing the CO2 in the equilibrating gas from 5 to up to 70%. In biceps (fast twitch) muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force decreased by 8%, but the rise and relaxation times of tetanic were not significantly changed. In soleus muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force was unchanged, but the rise and relaxation times of tetani were increased by 27 and 112%, respectively. In both muscles greater decreases in tetanic force were observed during repetitive or ischemic stimulation, which resulted in intracellular pH similar to that produced by hypercapnia. Contrary to previous reports, there was no significant decrease in PCr level in either muscle type with decreased intracellular pH. In the soleus at 30 degrees C there was a significant increase in PCr level with decreased pH.
 ...
PMID:Effect of decreased pH on force and phosphocreatine in mammalian skeletal muscle. 190 90

We superimposed extreme hypercapnia (arterial Pco2 400-450 mmHg) immediately before and during incomplete cerebral ischemia to distinguish the role of intracellular pH (pHi) and bicarbonate [( HCO3-]i) in postischemic metabolic and electrophysiological recovery. Incomplete global ischemia was produced in seven anesthetized dogs by 30 min of intracranial hypertension followed by 4 h of reperfusion. ATP, phosphocreatine (PCr), and pHi were measured with 31P magnetic resonance spectroscopy, and [HCO3-]i was calculated from the Henderson-Hasselbalch equation using the measured pHi and sagittal sinus Pco2. Cerebral blood flow was reduced to 7 +/- 1 ml.min-1.100 g-1 (+/- SE) during ischemia with extreme hypercapnia, and pHi decreased to 5.72 +/- 0.09. During normocapnic reperfusion, pHi rapidly returned to near baseline values by 14 min. [HCO3-]i fell from 12.1 +/- 0.9 to 6.0 +/- 1.2 mM by the midpoint of ischemia and recovered by 30 min of reperfusion. ATP, PCr, and O2 consumption also recovered rapidly and completely. Somatosensory-evoked potentials (SEP) recovered to 43 +/- 10% of control amplitude. These results are in marked contrast to the poor metabolic and SEP recovery previously observed in hyperglycemic dogs in which pHi decreased to the same range as with hypercapnic ischemia, but in which [HCO3-]i was much lower (1.1 +/- 0.5 mM). Therefore, [HCO3-]i depletion during hyperglycemic ischemia may be a more important factor in recovery than end-ischemic pHi per se. We speculate that higher [HCO3-]i may improve glial cell buffering capacity or decrease iron availability for hydroxyl radical production.
 ...
PMID:Bicarbonate conservation during incomplete cerebral ischemia with superimposed hypercapnia. 190 5

Peak tetanic tension was measured during acidosis resulting from either hypercapnia or repetitive tetanic stimulation in isolated, arterially perfused cat biceps brachii (predominantly fast twitch) or soleus (slow twitch) muscles. Phosphocreatine (PCr), Pi, intracellular pH (pHi), and extracellular pH (pHo) were monitored by 31P-nuclear magnetic resonance spectroscopy. During repetitive stimulation under normocapnic conditions (5% CO2, pHo 7.4) Pi increased, pHi decreased from 7.1 to 6.3, and there were significant correlations between both pHi and calculated [H2PO4-] vs. peak tetanic force in both muscle types. However, hypercapnic perfusion (70% CO2, pHo, 6.7, pHi 6.4-6.5) had no effect on peak tetanic force, and there was no significant correlation between pHi or [H2PO4-] during hypercapnia in either muscle. The results indicate that decreased peak tetanic force during repetitive stimulation is not directly due to changes in pHi or diprotonated phosphate.
 ...
PMID:Hypercapnic acidosis and increased H2PO4- concentration do not decrease force in cat skeletal muscle. 201 12

The tolerance of low intracellular pH (pHi) was examined in vivo in rats by imposing severe, prolonged respiratory acidosis. Rats were intubated and ventilated for 10 min with 20% CO2, for 75 min with 50% CO2, and for 10 min with 20% CO2. The maximum PaCO2 was 320 mm Hg. Cerebral intracellular lactate, pHi, and high-energy phosphate metabolites were monitored in vivo with 31P and 1H nuclear magnetic resonance (NMR) spectroscopy, using a 4.7-T horizontal instrument. Within 6 min after the administration of 50% CO2, pHi fell by 0.57 +/- 0.03 unit, phosphocreatine decreased by approximately 20%, and Pi increased by approximately 100%. These values were stable throughout the remainder of the hypercapnic period. Cerebral intracellular lactate, visible with 1H NMR spectroscopy in the hyperoxic state, decreased during hypercapnia, suggesting either a favorable change in oxygen availability (decreased lactate production) or an increase in lactate clearance or both. All hypercapnic animals awakened and behaved normally after CO2 was discontinued. Histological examination of cortical and hippocampal areas, prepared using a hematoxylin and eosin stain, showed no areas of necrosis and no glial infiltrates. However, isolated, scattered, dark-staining, shrunken neurons were detected both in control animals (no exposure to hypercapnia) and in animals that had been hypercapnic. This subtle histological change could represent an artifact resulting from imperfect perfusion-fixation, or it could represent subtle neurologic injury during the hypercapnia protocol. In summary, extreme hypercapnia and low pHi (approximately 6.5) are well tolerated in rats for periods up to 75 min if adequate oxygenation is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats. 230 43

The energy metabolism and the brain intracellular pH regulation under arterial CO2 tensions of 25-90 mm Hg were investigated in unanesthetized spontaneously breathing rats by in vivo phosphorus nuclear magnetic resonance spectroscopy (31P NMR). The 31P brain spectra, recorded with a high resolution spectrometer (AM 400 Brucker), allowed repeated non-invasive measurements of cerebral pH (pHi), phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) levels in 15 rats breathing a gas mixture containing 21% O2, N2, and a varied percentage of CO2. The pHi decreased significantly when the paCO2 was increased by hypercapnia. The percentage of pH regulation, estimated from the linear regression analysis of pHi versus the logarithm of the paCO2 was 78%. This result indicates that spontaneously breathing unanesthetized animals have better pHi regulation under hypercapnia investigated than that estimated for higher levels of hypercapnia in previous studies on unanesthetized animals, suggesting that there is a threshold for this highly efficient regulation. Furthermore, there were no significant correlations between the PCr, ATP and Pi levels and the paCO2 levels during hypercapnia. This indicates that physiological variations of the CO2 tension in the blood, and consequently in the brain parenchyma, have little effect on cerebral energy metabolism in unanesthetized spontaneously breathing animals.
 ...
PMID:Cerebral intracellular pH regulation during hypercapnia in unanesthetized rats: a 31P nuclear magnetic resonance spectroscopy study. 236 88


1 2 3 4 Next >>