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 metabolic effects of 60-min exposure to 250-2000 mg gamma-hydroxybutyrate (GHB) per kilogram or 150-1200 mg gamma-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, alpha-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivation of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.
 ...
PMID:A comparison of the effects of gamma-hydroxybutyrate and gamma-butyrolactone on cerebral carbohydrate metabolism. 4 Jun 77

1. The concentration of metabolites in intercostal and quadriceps muscle, and pulmonary function, were studied in twelve patients with chronic obstructive lung disease and acute respiratory failure before, during and after standardized treatment at an intensive care unit. The findings were compared with those obtained in hospitalized patients of comparable age with non-pulmonary diseases. 2. On admission, when the patients had marked hypoxaemia, hypercapnia and acidosis, the concentrations of ATP and creatine phosphate were low in both intercostal and quadriceps muscle, particularly the latter. The lactate concentration was increased in relation to control values but glycogen did not differ significantly. 3. In response to therapy, the Pa,CO2 and the patient's acidosis decreased, the vital capacity increased and lung mechanics improved along with the clinical condition. At the same time there were significant increases in the concentrations of ATP, creatine phosphate and glycogen in intercostal and quadriceps muscles, to values similar to, and for glycogen in excess of, those found in control subjects. Lactate concentration fell significantly during treatment. 4. In view of the low initial muscle concentrations of ATP and creatine phosphate in the patients, it is suggested that dysfunction of the respiratory muscles may be an important component of respiratory failure. Moreover, the concentration of energy-rich compounds in muscle rose significantly as the patients responded to treatment, which emphasizes the importance of adequate nutritional therapy in this disorder.
 ...
PMID:Muscle metabolism in patients with chronic obstructive lung disease and acute respiratory failure. 86 35

Ten mongrel dogs (mean weight: 27 kg) awake and with an implanted femoral catheter have been maintained for three days in a controlled chamber (10% CO2 and 21% O2). Arterial blood samples, taken before admission and after one, two, four, six, 24, 48 and 72 hours of exposure, allowed to study blood gases and acid-base equilibrium. Glycemia, phosphatemia, erythrocyte concentration of glucose-6-phosphate (G-6-P), fructose-6-phosphate (F-6-P), fructose-1,6-diphosphate (F-1,6-DP), 2,3-diphosphoglycerate (2,3-DPG), pyruvate, lactate and ATP were also titrated by various enzymatic methods. In addition, nine reference subjects were studied in air (without CO2). During the hypercapnia, [H+] rapidly increases to 70 nmol/1, then progressively decreases after 24 hours, while [HCO3-] slowly rises. The glycemia stays high during the whole exposure. There is also an increase in inorganic phosphate, G-6-P and F-6-P, but during the first 24 hours only. F-1,6-DP, pyruvate and lactate remain lowered during the whole exposure. The 2,3-DPG diminishes after the sixth hour. These phenomena, related to the acidosis and probably to the phosphofructokinase inhibition don't arise in the reference subjects. However the latter present after a two and four hour-stay in the chamber a small decrease in pyruvicemia and lactacidemia.
 ...
PMID:[Intermediates of erythrocyte glycolysis during three days hypercapnia in the dog (author's transl)]. 101 72

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

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

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

The ability of brain cells to regulate intracellular pH (pHi) and several phosphate metabolites was evaluated during 1 h of hypercapnia (inspiratory CO2 fraction of 0.10 and 0.05) in anesthetized rats by 31P high-field (145.6 MHz) nuclear magnetic resonance spectroscopy. Body temperature was maintained at 37 +/- 0.5 degrees C. Fully relaxed spectra were obtained for controls and 30-50 min after CO2 loading and CO2 withdrawal. Spectra were taken serially every 2.5 min after gas mixtures were changed. Brain pHi decreased 0.10 +/- 0.02 units [7.06 +/- 0.01 (SE)] to 6.96 +/- 0.01 (P less than 0.001) after 30-50 min of 10% CO2 breathing, and arterial pH decreased 0.24 +/- 0.01 units. Brain pHi decreased by 0.045 +/- 0.01 units (7.05 +/- 0.01 to 7.01 +/- 0.01, P less than 0.05) during 5% CO2 breathing. Brain pHi returned to control values after 30-50 min of CO2 washout in both groups. In three of six animals breathing 10% CO2, there was an undershoot in brain pHi by 0.07-0.09 units between 2.5 and 20 min of hypercapnia. Three animals exhibited an overshoot in pHi by 0.06-0.11 units between 7.5 and 17.5 min during CO2 washout. Phosphocreatine-to-Pi and Pi-to-beta-ATP ratios changed during hypercapnia and returned to base line after withdrawal of CO2. The findings of a smaller brain pHi change than arterial pH change and undershoots and overshoots in pHi support the view that pHi regulation involves active processes such as transmembrane ion transport.
 ...
PMID:Effects of hypercapnia on brain pHi and phosphate metabolite regulation by 31P-NMR. 250 Dec 77

The effects of respiratory acidosis on renal inorganic phosphate (Pi) handling are controversial. Clearance experiments, therefore, were performed in fasted, chronically parathyroidectomized (PTX), dietary Pi-deprived rats. The objectives were twofold: to study the effects of compensated and uncompensated hypercapnia per se on renal Pi excretion and to examine the interaction between acute hypercapnia, dietary Pi, and parathyroid hormone (PTH) on the renal handling of Pi. Acute hypercapnia increased the plasma Pi (delta 2.82 +/- 0.65 mg/dl, P less than 0.05) without altering the glomerular filtration rate (GFR). The FEPi increased (delta 7.26 +/- 0.48%, P less than 0.001) but the TRPi/GFR also increased. PTH (3 U X kg-1 X h-1) superimposed on hypercapnia resulted in a plasma Pi comparable to hypercapnia alone. The FEPi (7.56 +/- 0.78 vs. 24.43 +/- 2.20%; P less than 0.001) was higher and the TRPi/GFR (117 +/- 4 vs. 80 +/- 2 micrograms/min, P less than 0.01) lower, in the former group. PTH infusion during normocapnia resulted in a lower FEPi (0.20 +/- 0.10 vs. 24.43 +/- 2.20%, P less than 0.001) and a higher TRPi/GFR (106 +/- 2 vs. 80 +/- 2 micrograms/min, P less than 0.01) compared with PTH infusion during hypercapnia. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion was similar between the groups. During hypercapnia, when the extracellular acidemia was neutralized, the phosphaturic action of PTH persisted. These studies offer direct evidence that in chronically PTX, dietary Pi-deprived rats, the phosphaturic action of PTH is restored by hypercapnia per se. This effect appears to be independent of extracellular acidemia, changes in the plasma Pi and calcium, urinary pH and Na and cAMP excretion.
 ...
PMID:Effect of acute hypercapnia on PTH-stimulated phosphaturia in dietary Pi-deprived rat. 303 23


1 2 3 4 Next >>