phosphocreatine and Hypercapnia

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Brain; Brain Edema; Humans; Hypercapnia; Hypoxia, Brain; Ischemic Attack, Transient; Lactates; Phosphocreatine; Pyruvates

To estimate the exchange rate of creatine (Cr) CEST and to evaluate the pH sensitivity of guanidinium (Guan) CEST in the mouse brain.. Polynomial and Lorentzian line-shape fitting (PLOF) were implemented to extract the amine, amide, and Guan CEST signals from the brain Z-spectrum at 11.7T. Wild-type (WT) and knockout mice with the guanidinoacetate N-methyltransferase deficiency (GAMT. Comparison between the Z-spectra of WT and GAMT. The in vivo CrCEST exchange rate is slow, and the acquisition parameters for the CrCEST should be adjusted accordingly. CrCEST is the major contribution to the opposite pH-dependence of GuanCEST signal under different conditions of B

Topics: Animals; Brain; Creatine; Hypercapnia; Magnetic Resonance Imaging; Mice; Phosphocreatine

There is significant controversy over the effects of hypercapnia on the human newborn brain. Previous studies have shown that 1 h of an arterial CO2 pressure (Paco2) of 80 mm Hg alters brain cell membrane Na+K+-ATPase enzyme activity in the cerebral cortex of newborn piglets. The present study tests the hypothesis that hypercapnia (either a Paco2 of 65 or 80 mm Hg) results in decreased energy metabolism and alters neuronal nuclear enzyme activity and protein expression, specifically Ca++/calmodulin-dependent kinase (CaMK) IV activity, phosphorylation of cAMP response element binding protein (CREB), and expression of apoptotic proteins in cortical neuronal nuclei of newborn piglets. Studies were performed in 20 anesthetized normoxic piglets ventilated at either a Paco2 of 65 mm Hg, 80 mm Hg, or 40 mm Hg for 6 h. Energy metabolism was documented by ATP and phosphocreatine (PCr) levels. Results show ATP and PCr levels were significantly lower in the hypercapnic groups than the normocapnic. CaMK IV activity, phosphorylated CREB density, and Bax protein expression were all significantly higher in the hypercapnic groups than the normocapnic group. Bcl-2 protein was similar in all three groups, making the ratio of Bax/Bcl-2 significantly higher in the hypercapnic groups than in the normocapnic group. We conclude that hypercapnia alters neuronal energy metabolism, increases phosphorylation of transcription factors, and increases the expression of apoptotic proteins in the cerebral cortex of newborn piglets and therefore may be deleterious to the newborn brain.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; bcl-2-Associated X Protein; Blotting, Western; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 4; Carbon Dioxide; Carrier Proteins; Cell Nucleus; Cerebral Cortex; Cyclic AMP; Hydrogen-Ion Concentration; Hypercapnia; Neurons; Phosphocreatine; Phosphorylation; Pressure; Protein Kinases; Proto-Oncogene Proteins c-bcl-2; Sodium-Potassium-Exchanging ATPase; Swine; Time Factors

Chemoreceptors in the ventral medulla contribute to the respiratory response to hypercapnia. Do they 'sense' intracellular pH (pHi)? We measured pHi in the ventral medulla or cortex (control) using 31P-NMR obtained via a novel 3 x 5 mm2 surface coil in anesthetized rats breathing air or 7% CO2. During air breathing over 240 min, pHi decreased slightly from 7.13 +/- 0.02 to 7.05 +/- 0.02 (SEM; n = 5; 2 cortex, 3 ventral medulla). During 180 min of hypercapnia, cortical pHi (n = 4) decreased from 7.17 +/- 0.02 to 6.87 +/- 0.01 by 90 min and recovered by 150 min. Ventral medulla pHi showed no such regulation. It decreased from 7.11 +/- 0.02 to 6.88 +/- 0.02 at 90 min and recovered only after cessation of hypercapnia (n = 5), results consistent with pHi being the chemoreceptor stimulus. However, non-chemoreceptor neurons that contribute to our medullary NMR signal also do not appear to regulate pHi in vitro. Regional differences in pHi regulation between cortex and ventral medulla may be due to both chemosensitive and non-chemosensitive neurons.

Topics: Adenosine Triphosphatases; Animals; Blood Gas Analysis; Cerebral Cortex; Hydrogen-Ion Concentration; Hypercapnia; Kinetics; Magnetic Resonance Spectroscopy; Medulla Oblongata; Phosphates; Phosphocreatine; Phosphorus; Rats; Rats, Sprague-Dawley; Time Factors

The relationships between oxygen consumption (Q(O2)) and calculated cytoplasmic ADP concentration ([ADP]) and the free energy of ATP hydrolysis (deltaG(ATP)) were examined in ex vivo arterially perfused cat soleus muscles during repetitive twitch stimulation under normocapnic (5% CO2) and hypercapnic (70% CO2) conditions. Hypercapnia decreased extra- and intracellular pH by over 0.5 but had no significant effect on Q(O2) or phosphocreatine (PCr)/ATP in muscles at rest. The maximum Q(O2) measured during stimulation and the rate constant for PCr recovery after stimulation both decreased during hypercapnic compared with normocapnic perfusion, but the estimated ATP/O2 was unchanged. The change in PCr and deltaG(ATP) with increasing Q(O2) was greater during hypercapnic compared with normocapnic stimulation, as expected from the decrease in maximum Q(O2). However, the relationships between Q(O2) and [ADP] and deltaG(ATP) were both shifted to the left during hypercapnia compared with normocapnia. The results show that changes in cytoplasmic adenine nucleotides and phosphate are not sufficient to explain the control of respiration in skeletal muscle. However, in the context of thermodynamic models of respiratory control, the results can be explained by increased intramitochondrial potential for ATP synthesis at low pH.

Topics: Acidosis; Animals; Cats; Electric Stimulation; Homeostasis; Hydrogen-Ion Concentration; Hypercapnia; Magnetic Resonance Spectroscopy; Muscle, Skeletal; Oxygen Consumption; Phosphocreatine

We studied the effects of graded acidosis (both CO2 and lactic acid) and anoxia on intracellular pH (pHi) regulation, high-energy phosphates, and mechanical function of isolated perfused hearts of the turtle (Chrysemys picta bellii) at 20 degrees C using 31P-nuclear magnetic resonance (NMR) spectroscopy. During CO2 acidosis, anoxia had no effect on apparent nonbicarbonate buffer value (d[HCO3-]/dpHi = 71 and 89 mM/pH in normoxia and anoxia, respectively) or on pHi regulation (dpHi/dpHe = 0.52 and 0.43 in normoxia and anoxia, respectively, where pHe is extracellular pH). During normoxic lactic acidosis, dpHi/dpHe was similar to the values observed in CO2 acidosis and averaged 0.55 overall. During anoxic lactic acidosis, however, similar regulation occurred over only a narrow range of pHe, and then dpHi/dpHe increased to greater than 1.0 at pHe less than 7.1. Creatine phosphate (CP), calculated as the area of the NMR peak, fell more in response to normoxic CO2 acidosis than to normoxic lactic acidosis; in anoxia, the fall in CP was further increased but to similar extreme levels (10-20% of control) in both acid perfusions. Cardiac output and maximum rate of pressure development each fell during acidosis in similar fashion in all protocols, and the responses were similar in normoxic and anoxic hearts. Heart rate, in contrast, decreased during acidosis, but this effect was more pronounced when hearts were anoxic. We conclude that the effect of acidosis on cardiac function can depend on the type of acidosis imposed. Based on the heart's insensitivity to anoxia alone, we suggest that anoxia may normally depress function indirectly via its effect on intracellular acid-base state.

Topics: Acidosis, Lactic; Adenosine Triphosphate; Animals; Carbon Dioxide; Female; Heart; Heart Rate; Hydrogen-Ion Concentration; Hypercapnia; Hypoxia; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Myocardium; Oxygen; Phosphocreatine; Phosphorus; Turtles

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.

Topics: Adenosine Triphosphate; Animals; Bicarbonates; Blood Glucose; Blood Pressure; Brain; Carbon Dioxide; Cerebrovascular Circulation; Dogs; Evoked Potentials, Somatosensory; Hydrogen-Ion Concentration; Hypercapnia; Ischemic Attack, Transient; Magnetic Resonance Spectroscopy; Oxygen Consumption; Partial Pressure; Phosphocreatine; Reperfusion

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.

Topics: Acidosis; Adenosine Triphosphate; Animals; Cats; Female; Hydrogen-Ion Concentration; Hypercapnia; In Vitro Techniques; Kinetics; Magnetic Resonance Spectroscopy; Male; Muscle Contraction; Muscles; Perfusion; Phosphates; Phosphocreatine

We have reported previously that, when exposed to hypercapnia of various intensities, the diaphragm reduces its force of twitch and tetanic contractions in the in vitro rat preparation as well as in the in vivo dog preparation. The experiments reported here with 31P nuclear magnetic resonance (31P-NMR) spectroscopy attempt to examine cellular mechanisms that might be responsible for this deterioration in mechanical performance. Specifically they describe certain characteristics of this preparation and cautions needed to study the resting in vitro rat diaphragm with such techniques. Second, they report the response of intracellular pH (pHi), phosphocreatine (PCr), ATP, and inorganic phosphate (Pi) in the resting in vitro rat diaphragm exposed to long-term normocapnia or to long-term hypercapnia. The results show that 1) to maintain a viable preparation, it was necessary to keep the diaphragm extended to an area approximating that at functional residual capacity, 2) the diaphragm seemed quite capable of maintaining a constant pHi and constant contents of ATP and Pi during normocapnia, but there was a gradual decline in PCr, and 3) during hypercapnia there was a significant decrease in pHi, but the behavior of the phosphate metabolites was exactly as during normocapnia. The results suggest that the decrease in mechanical performance of the diaphragm is probably not due to a decrease in the availability of the high-energy phosphates, although they do not completely exclude this possibility or possibilities related to regional compartmentation.

Topics: Adenosine Triphosphate; Animals; Diaphragm; Hydrogen-Ion Concentration; Hypercapnia; In Vitro Techniques; Magnetic Resonance Spectroscopy; Muscle Relaxation; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains

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.

Topics: Acid-Base Equilibrium; Acute Disease; Adenosine Triphosphate; Aged; Energy Metabolism; Female; Humans; Hypercapnia; Hypoxia; Lactates; Lactic Acid; Lung Diseases, Obstructive; Male; Middle Aged; Muscles; Phosphocreatine; Respiratory Insufficiency

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.

Topics: Adenosine Diphosphate; Anesthesia, General; Animals; Brain; Electroencephalography; Halothane; Hypercapnia; Isoflurane; Magnetic Resonance Spectroscopy; Methyl Ethers; Phosphocreatine; Rats; Rats, Inbred Strains

31P nuclear magnetic resonance (NMR) spectroscopy was used noninvasively to measure in vivo changes in intracellular pH and intracellular phosphate metabolites in the brains of rats during supercarbia (PaCO2 greater than or equal to 400 mm Hg). Five intubated rats were mechanically ventilated with inspired gas mixtures containing 70% CO2 and 30% O2. Supercarbia in the rat was observed to cause a greater reduction in cerebral intracellular pH (pHi) and increase in PCO2 than observed in other experiments with rats after 15 min of global ischemia. Complete neurologic and metabolic recovery was observed in these animals, despite and average decrease in pHi of 0.63 +/- 0.02 pH unit during supercarbia episodes that raised PaCO2 to 490 +/- 80 mm Hg. No change was observed in cerebral intracellular ATP and only a 25% decrease was detected in phosphocreatine. The concentration of free cerebral intracellular ADP, which can be calculated if one assumes that the creatine kinase reaction is in equilibrium, decreased to approximately one-third of its control value. The calculated threefold decrease in the concentration of free ADP and twofold increase in the cytosolic phosphorylation potential suggest that there is increased intracellular oxygenation during supercarbia. Because a more than fourfold increase in intracellular hydrogen ion concentration was tolerated without apparent clinical injury, we conclude that so long as adequate tissue oxygenation and perfusion are maintained, a severe decrease in intracellular pH need not induce or indicate brain injury.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Blood Gas Analysis; Brain; Extracellular Space; Hydrogen-Ion Concentration; Hypercapnia; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus; Rats; Rats, Inbred Strains

Topics: Acute Disease; Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Ammonia; Animals; Bicarbonates; Blood; Body Temperature; Brain; Carbon Dioxide; Citric Acid Cycle; Glucose; Hydrogen-Ion Concentration; Hypercapnia; Ketoglutaric Acids; Lactates; Malates; Male; Nitrous Oxide; Phosphocreatine; Pyruvates; Rats; Temperature; Time Factors

Topics: Adenine Nucleotides; Anesthesia, General; Animals; Brain; Carbon Dioxide; Citric Acid Cycle; Depression, Chemical; Glycolysis; Halothane; Hydrogen-Ion Concentration; Hypercapnia; Hyperventilation; Lactates; Male; Nitrous Oxide; Organophosphorus Compounds; Phenobarbital; Phosphocreatine; Pyruvates; Rats; Stimulation, Chemical

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Body Fluids; Brain; Brain Chemistry; Carbon Dioxide; Creatine; Cytoplasm; Fluorometry; Hydrogen-Ion Concentration; Hypercapnia; Lactates; Male; NAD; Phosphocreatine; Pyruvates; Rats

Topics: Acid-Base Equilibrium; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Bicarbonates; Blood Pressure; Body Temperature; Brain; Brain Chemistry; Carbon Dioxide; Creatine; Creatine Kinase; Hemoglobins; Hydrogen-Ion Concentration; Hypercapnia; Male; Oxygen; Phosphocreatine; Rats

Topics: Acute Disease; Animals; Brain Chemistry; Carbon Dioxide; Chronic Disease; Glutamates; Hydrogen-Ion Concentration; Hypercapnia; Ketoglutaric Acids; Lactates; Male; Phosphocreatine; Pyruvates; Rats; Time Factors

Topics: Acid-Base Equilibrium; Adenine Nucleotides; Animals; Brain Injuries; Humans; Hypercapnia; Hyperventilation; Hypoxia; Intracranial Pressure; Lactates; Phosphocreatine; Pyruvates; Rats; Time Factors

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Bicarbonates; Brain; Brain Chemistry; Carbon Dioxide; Cats; Creatinine; Female; Hypercapnia; Hyperventilation; Hypoxia, Brain; Lactates; Male; Phosphocreatine; Pyruvates

Topics: Adenosine Triphosphate; Animals; Electrocardiography; Guinea Pigs; Hypercapnia; Hypoxia; Male; Myocardium; NADP; Oxidation-Reduction; Phosphocreatine