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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationships between pHi (intracellular pH) and phosphate compounds were evaluated by nuclear magnetic resonance (NMR) in normo-, hypo-, and hypercapnia, obtained by changing fractional inspired concentration of CO2 in dogs anesthetized with 0.75% isoflurane and 66% N2O. Phosphocreatine (PCr) fell by 2.02 mM and Pi (inorganic phosphate) rose by 1.92 mM due to pHi shift from 7.10 to 6.83 during hypercapnia. The stoichiometric coefficient was 1.05 (r2 = 0.78) on log PCr/Cr against pHi, showing minimum change of ADP/ATP and equilibrium of creatine kinase in the pH range of 6.7 to 7.25. [ADP] varied from 21.6 +/- 4.1 microM in control (pHi = 7.10) to 26.8 +/- 6.3 microM in hypercapnia (pHi = 6.83) and 24.0 +/- 6.8 microM in hypocapnia (pHi = 7.17). ATP/ADP X Pi decreased from 66.4 +/- 17.1 mM-1 during normocapnia to 25.8 +/- 6.3 mM-1 in hypercapnia. The ADP values are near the in vitro Km; thus ADP is the main controller. The velocity of oxidative metabolism (V) in relation to its maximum (Vmax) as calculated by a steady-state Michaelis-Menten formulation is approximately 50% in normocapnia. In acidosis (pH 6.7) and alkalosis (pH 7.25), V/Vmax is 10% higher than the normocapnic brain. This increase of V/Vmax is required to maintain cellular homeostasis of energy metabolism in the face of either inhibition at extremes of pH or higher ATPase activity.
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PMID:Relationship between intracellular pH and energy metabolism in dog brain as measured by 31P-NMR. 359 78

Quadriceps femoris muscle needle biopsies were performed in ten patients with chronic obstructive pulmonary disease and acute respiratory failure and in ten age- and sex-matched healthy control subjects. The main indices of skeletal muscle cell energy metabolism, intracellular acid-base equilibrium and lactate metabolism were evaluated. Reduced ATP and phosphocreatine content, intracellular acidosis related to hypercapnia, increased muscle lactate without alterations of the muscle lactate concentration gradient were observed in the skeletal muscle of the hypercapnic-hypoxemic COPD patients studied, in which group no correlation was found between hypoxia and energy or lactate metabolism parameters. These results suggest that an overall derangement of cell energy metabolism and acid-base equilibrium is present in severely hypercapnic-hypoxemic chronic obstructive pulmonary disease and that in this condition skeletal muscle seems to metabolize anaerobically-even though, in addition to hypoxia, other factors interfering with both cell energy and lactate metabolism are likely to be present.
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PMID:Skeletal muscle energetics, acid-base equilibrium and lactate metabolism in patients with severe hypercapnia and hypoxemia. 366 4

Qualitatively different responses of ADP levels have previously been observed in the brain during hypercarbia. One investigation has found that cerebral ADP stayed constant during hypercarbia in rats that were anesthetized with halothane, while another observed that ADP decreased during supercarbia in rats that received no supplemental anesthesia. This article reports an in vivo 31P nuclear magnetic resonance study to test the hypothesis that halothane anesthesia accounts for the discrepant observations. Isoflurane anesthesia was also studied in a second group of rats to see if a different general anesthetic agent would cause the same effects that halothane causes. The two groups of five rats underwent dual episodes of hypercarbia that were separated by a 45-min recovery period. General anesthesia, either 0.5% halothane or 1.0% isoflurane, was administered during the first episode but not during the second. Hypercarbia during halothane anesthesia caused the measured phosphocreatine (PCr) to decrease by 40%, while the calculated change in ADP was 10%, in agreement with the former investigation. In contrast, hypercarbia during either isoflurane anesthesia or no anesthesia caused a decrease of only 10% in PCr, which meant that the calculated decrease in ADP was 60%, in agreement with the results of the second investigation. We conclude that during hypercarbia, clinical concentrations of halothane, unlike clinical concentrations of isoflurane, interfere with the regulation of ATP metabolism.
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PMID:Cerebral intracellular ADP concentrations during hypercarbia: an in vivo 31P nuclear magnetic resonance study in rats. 371 Nov 64

To examine the possible contribution of active H+ secretion mediated by brush border enzymes to proximal tubule HCO-3 absorption, paired reperfusions of surface proximal convoluted tubules were performed with the inhibitor dicyclohexylcarbodiimide (DCCD). In control studies using a solution devoid of HCO-3 but containing 5.5 mM glucose, 1 mM DCCD had no effect on glucose or fluid (Na+) absorption, suggesting that this inhibitor did not interfere with sodium entry at the brush border or mitochondrial energy production (ATP synthesis). In experiments using a perfusion solution containing 18-25 mM HCO-3, DCCD caused a fall in absolute CO2 absorption of approximately 15% under eucapneic conditions and 30% during acute hypercapnia. One millimole per liter amiloride (an inhibitor of the passive Na+-H+ exchanger) caused a 15% inhibition of CO2 absorption during acute hypercapnia and a disproportionately large reduction in fluid (Na+) absorption. The latter was not due to cell poisoning, since 1 mM amiloride had no inhibitory effect on fluid or glucose absorption when a HCO-3-free perfusion solution was used. Addition of 1 mM DCCD to a perfusion solution containing either 10(-3) M amiloride or 10(-4) M acetazolamide caused a significant inhibition of CO2 absorption compared with amiloride or acetazolamide alone. The observations are consistent with the view that in addition to passive Na+-H+ exchange, active transport mediated by either a H+-ATPase or a redox-driven H+ pump in the brush border contributes significantly to HCO-3 absorption in the proximal tubule.
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PMID:Evidence for a DCCD-sensitive component of proximal bicarbonate reabsorption. 406 52

Blood flow and high energy phosphate (HEP) content were determined simultaneously in multiple microregions of the left ventricular subendocardium in 49 anaesthetized open-chest rabbits, to determine the relationship between the parameters during high O2 supply with hypercapnia and chromonar treatment. ATP and CP content were quantitated in quick-frozen hearts by fluorometry in 1-2 mg sites where perfusion was measured by H2 clearance employing bare-tipped platinum electrodes. Both hypercapnia and chromonar elevated subendocardial tissue perfusion approximately 30% and O2 supply 45% above control. Blood flow was normally distributed with either treatment, but was more homogeneous with hypercapnia. Neither treatment altered absolute levels of either HEP, but the variance of ATP was less than control. CP distribution was normal in both treatments. There was no significant linear correlation between blood flow and HEP under hypercapnia or chromonar treatment. We conclude that tissue HEP content is a variable not only dependent on O2 supply and blood flow, but also on the size of the ATP and CP pool and the energy demand of the local microregion. The variability of ATP in microregions of the rabbit subendocardium is reduced under conditions of high O2 supply.
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PMID:Microregional blood flow and high energy phosphates under conditions of high O2 supply in left ventricular subendocardium. 619 84

Intramuscular (m. quadriceps) contents of electrolytes, free amino acids and energy-rich phosphagens were determined in 12 patients (51--81 years of age) with moderate chronic obstructive lung disease. At the time of the study the patients were in their habitual condition. After an overnight rest, 8 patients showed hypoxia and five of these also hypercapnia. Compared to apparently healthy controls of similar age and studied under identical conditions, the patients had increased intramuscular concentrations of sodium, chloride and extracellular water, whereas magnesium was slightly reduced. ATP and phosphocreatine, as well as the ATP/ADP and phosphocreatine/total creatine ratios, were reduced. The ATP/ADP ratio correlated significantly to intracellular magnesium. Plasma amino acids were essentially similar in controls and patients but the intramuscular contents of essential amino acids and of the three branched-chain amino acids were slightly enhanced in the patients.
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PMID:Energy-rich phosphagens, electrolytes and free amino acids in leg skeletal muscle of patients with chronic obstructive lung disease. 708 Aug 63

Hypoxia impairs brain function by incompletely defined mechanisms. Mild hypoxia, which impairs memory and judgment, decreases acetylcholine (ACh) synthesis, but not the levels of ATP or the adenylate energy charge. However, the effects of mild hypoxia on the synthesis of the glucose-derived amino acids [alanine, aspartate, gamma-amino butyric acid (GABA), glutamate, glutamine, and serine] have not been characterized. Thus, we examined the incorporation of [U-14C]glucose into these amino acids and ACh during anemic hypoxia (injection of NaNO2), hypoxic hypoxia (15 or 10% O2), and hypoxic hypoxia plus hypercarbia (15 or 10% O2 with 5% CO2). In general, the synthesis of the amino acids and of ACh declined in parallel with each type of hypoxia we studied. For example, anemic hypoxia (75 mg/kg of NaNO2) decreased the incorporation of [U-14C]glucose into the amino acids and into ACh similarly. [Percent inhibition: ACh (57.4), alanine (34.4), aspartate (49.2), GABA (61.9), glutamine (59.2), glutamate (51.0), and serine (36.7)]. A comparison of several levels (37.5, 75, 150, 225 mg/kg of NaNO2) of anemic hypoxia showed a parallel decreased in the flux of glucose into ACh and into the amino acids whose synthesis depends on mitochondrial oxidation: GABA (r = 0.98), glutamate (r = 0.99), aspartate (r = 0.96), and glutamine (r = 0.97). The synthesis of the amino acids not dependent on mitochondrial oxidation did not correlate as well with changes in ACh metabolism: serine (r = 0.68) and alanine (r = 0.76). The decreases in glucose incorporation into ACh and into the amino acids with hypoxic hypoxia (15% or 10% O2) or hypoxic hypoxia with 5% CO2 were very similar to those with the two lowest levels of anemic hypoxic. Thus, and explanation of the brain's sensitivity to a decrease in oxygen availability must include the alterations in the metabolism of the amino acid neurotransmitters as well as ACh.
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PMID:Decreases in amino acids and acetylcholine metabolism during hypoxia. 725 4

This study explores the influence of severe lactic acidosis in the ischemic rat brain on postischemic recovery of the tissue energy state and neurophysiological parameters. Severe incomplete brain ischemia (cerebral blood flow below 5% of normal) was induced by bilateral carotid artery clamping combined with hypovolemic hypotension. We varied the production of lactate in the tissue by manipulating the blood glucose concentrations. A 30-min period of incomplete ischemia induced in food-deprived animals caused lactate to accumulate to 15-16 mumol g-1 in cortical tissue. Upon recirculation these animals showed: (1) a considerable recovery of the cortical energy state as evaluated from the tissue concentrations of phosphocreatine, ATP, ADP, and AMP; and (2) return of spontaneous electrocortical activity as well as of somatosensory evoked response (SER). In contrast, administration of glucose to food-deprived animals prior to ischemia caused an increase in tissue lactate concentration to about 35 mumol g-1. These animals did not recover energy balance in the tissue and neurophysiological functions did not return. In other experiments the production of lactate during 30 min of complete compression ischemia was increased from about 12 mumol g-1 (normoglycemic animals) to 20-30 mumol g-1 by preischemic hyperglycemia and, in separate animals, combined hypercapnia. The recovery of the cortical energy state upon recirculation was significantly poorer in hyperglycemic animals. It is concluded that a high degree of tissue lactic acidosis during brain ischemia impairs postischemic recovery and that different degrees of tissue lactic acidosis may explain why severe incomplete ischemia, in certain experimental models, is more deleterious than complete brain ischemia.
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PMID:Brain lactic acidosis and ischemic cell damage: 1. Biochemistry and neurophysiology. 732 45

Previously we have shown that hypercarbia produces a larger decrease in agonal glycolytic rate in 1-month-old swine than in newborns. In an effort to understand the mechanism responsible for this difference, we tested the hypothesis that hypercarbia produces age-related changes in the concentration of one or more effectors of phosphofructokinase activity. Specifically, in vivo 31P and 1H NMR spectroscopy was used to compare changes in lactate levels, intracellular pH, free magnesium concentration, and content of phosphorylated metabolites for these two age groups at three intervals during the first 1.5 min of complete ischemia in the presence or absence of hypercarbia (PaCO2 = 102-106 mm Hg). Hypercarbia produced the same drop in intracellular brain pH for both age groups, but the decrease in phosphocreatine level and increase in inorganic phosphate content were greater in 1-month-olds compared with newborns. During ischemia there was no difference between the magnitude of change in intracellular pH and levels of phosphocreatine and inorganic phosphate in hypercarbic 1-month-olds versus newborns. Under control conditions, i.e., normocarbia and normoxia, the free Mg2+ concentration was lower and the fraction of magnesium-free ATP was higher for newborns than 1-month-olds. However, there was no change in these variables for either age group during hypercarbia and early during ischemia. Thus, age-related differences in the relative decrease in agonal glycolytic rate during hypercarbia could not be explained by differences in intracellular pH, inorganic phosphate content, or free magnesium concentration. The [ADP]free at control was higher in newborns compared with 1-month-olds, and there was no age-related difference in [AMP]free. These variables did not change for newborns when exposed to hypercarbia, but for 1-month-olds [ADP]free and [AMP]free increased during hypercarbia relative to control values. High-energy phosphate utilization during ischemia for hypercarbic 1-month-olds was reduced by 74% compared with normocarbic 1-month-olds during ischemia, whereas the reduction in energy utilization (14%) was not significant for hypercarbic versus normocarbic newborns during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evaluation of potential effectors of agonal glycolytic rate in developing brain measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy. 779 28

The effect of hypercapnia on brain cell membrane structure and function was studied in anesthetized newborn piglets. Lipid peroxidation products (conjugated dienes and fluorescent compounds), Na+,K(+)-ATPase activity and enzyme affinity to ATP (substrate), K+ and Na+ ions (activators), and strophanthidin (inhibitor) were measured in three groups of animals: controls, those exposed to 90 minutes of PaCO2 > 80 mmHg (hypercapnia) and those exposed the same way, following restoration of normal PaCO2 (recovery). Enzyme activity was unchanged by hypercapnia, but enzyme affinity was altered as indicated by an increase in ATP affinity. Affinities to Na+, K+, and strophanthidin were unchanged. Restoration of normal PaCO2 resulted in an increase in conjugated dienes. The data demonstrate that hypercapnia followed by restoration of normal PaCO2 in healthy term newborn piglets is associated with mild modification of brain cell membrane Na+,K(+)-ATPase, possibly due to lipid peroxidation.
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PMID:Brain cell membrane modification following hypercapnia and recovery in newborn piglets. 797 Sep 23


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