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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of halothane and sevoflurane on cat brain energy metabolism and regional cerebral blood flow (rCBF) were evaluated during normo- and hypocapnia. Brain energy status was evaluated with phosphorous nuclear magnetic resonance spectroscopy (31P-MRS) and rCBF was measured by the hydrogen clearance method. A high concentration of halothane (3 MAC) impaired brain energy metabolism, while even a higher concentration of sevoflurane (4 MAC) had no untoward effect on brain energy metabolism. At 3 MAC of halothane, there were measurable decreases in brain phosphocreatine (69% of the control) and increases in brain inorganic phosphate (about 250% of control Pi), even though CBF was about 70% of the control value. During hypocapnia, the phosphocreatine levels began to decrease at a Paco2 of 2.7 kPa with 2 MAC of sevoflurane (90% of the control), and at a Paco2 of 4.0 kPa with 2 MAC of halothane (92% of the control). rCBF had decreased to less than 50% of the control value when Paco2 was < or = 2.7 kPa with 2 MAC of sevoflurane and < or = 4.0 kPa with 2 MAC of halothane. Abnormal brain energy metabolism was only observed when rCBF was decreased to less than half of the control (non-anesthetized and normocapnic) value. Following administration of a vasopressor, metaraminol, the abnormal brain energy metabolism induced by 2 MAC of halothane at a Paco2 of 1.33 kPa was normalized in parallel with the improved rCBF values. We conclude that hyperventilation and fluctuating blood pressure contribute to the occurrence of abnormal brain energy metabolism during halothane and sevoflurane anesthesia. This is more pronounced with halothane than with sevoflurane. The hypocapnia-induced abnormality during exposure to 2 MAC of either agent was due to decreased CBF associated with low perfusion pressure, indicating that there was no direct effect of these anesthetics on cerebral energy metabolism.
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PMID:Brain energy metabolism and blood flow during sevoflurane and halothane anesthesia: effects of hypocapnia and blood pressure fluctuations. 827 58

The effects of halothane and sevoflurane on cat brain energy metabolism and regional cerebral blood flow (rCBF) were evaluated during normo- and hypocapnia. Brain energy status was evaluated with phosphorous nuclear magnetic resonance spectroscopy (31P-MRS) and rCBF was measured by the hydrogen clearance method. A high concentration of halothane (3 MAC) impaired brain energy metabolism, while even a higher concentration of sevoflurane (4 MAC) had no untoward effect on brain energy metabolism. At 3 MAC of halothane, there were measurable decreases in brain phosphocreatine (69% of the control) and increases in brain inorganic phosphate (about 250% of control Pi), even though CBF was about 70% of the control value. During hypocapnia, the phosphocreatine levels began to decrease at a PaCO2 of 2.7 kPa with 2 MAC of sevoflurane (90% of the control), and at a PaCO2 of 4.0 kPa with 2 MAC of halothane (92% of the control). rCBF had decreased to less than 50% of the control value when PaCO2 was < or = 2.7 kPa with 2 MAC of sevoflurane and < or = 4.0 kPa with 2 MAC of halothane. Abnormal brain energy metabolism was only observed when rCBF was decreased to less than half of the control (non-anesthetized and normocapnic) value. Following administration of a vasopressor, metaraminol, the abnormal brain energy metabolism induced by 2 MAC of halothane at a PaCO2 of 1.33 kPa was normalized in parallel with the improved rCBF values. We conclude that hyperventilation and fluctuating blood pressure contribute to the occurrence of abnormal brain energy metabolism during halothane and sevoflurane anesthesia. This is more pronounced with halothane than with sevoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain energy metabolism and blood flow during sevoflurane and halothane anesthesia: effects of hypocapnia and blood pressure fluctuations. 806 34

The present study tests the hypothesis that cerebral ischemia induced by severe hypocapnia modifies the N-methyl-D-aspartate (NMDA) receptor/ion channel complex in the cerebral cortical cell membranes of newborn piglets. Studies were performed in six newborn piglets subjected to ischemic hypoxia induced by hyperventilation (PaCO2, 9-11 mmHg) for 1 h. Comparisons were made to a normoxic group on room air (n = 6). Following hyperventilation, phosphocreatine decreased 80%, but ATP remained unchanged. NMDA receptor activation was determined by measuring [3H]MK-801 binding at concentrations varying from 2.5 to 50 nM. Following hyperventilation, Bmax decreased 52% to 0.50 +/- 0.04 pmol/mg protein (P = 0.001); however, the Kd value was unchanged at 7.45 +/- 0.79 nM. Spermine and magnesium dependent activation of the NMDA receptor was determined in the hyperventilated and control groups. With spermine concentrations increasing from 2.5 to 50 microM the maximal spermine dependent activation in the normoxic group was 13.7 +/- 7.93% which occurred at a concentration of 3.75 +/- 1.37 microM. In the hyperventilated group maximal activation was 32.4 +/- 23.5% (P = 0.095) at 4.58 +/- 2.46 microM (P = ns). With magnesium concentrations increasing from 2.5 to 100 microM the maximal magnesium dependent activation in the normoxic group was 17.0 +/- 13.6% which occurred at a concentration of 22.5 +/- 6.12 microM. In the hyperventilated group maximal activation was 26.3 +/- 14.9% (P = ns) at 4.58 +/- 2.92 microM (P < 0.0001). These data show that with less severe tissue hypoxia, as evidenced by conservation of ATP, there is less modification of the NMDA receptors. Ischemia induced by hyperventilation leads to an increase in spermine activation of the NMDA receptor, and the NMDA receptor is much more sensitive to magnesium as evidenced by the maximal activation occurring at a significantly lower magnesium concentration. Ischemia induced by hyperventilation modifies the spermine, magnesium, and MK-801 binding sites of the NMDA receptor and may result in increased NMDA receptor mediated neurotoxicity in the newborn brain.
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PMID:Modification of the N-methyl-D-aspartate (NMDA) receptor in the brain of newborn piglets following hyperventilation induced ischemia. 893 73

We previously have demonstrated that hypocapnia aggravates and hypercapnia protects the immature rat from hypoxic-ischemic brain damage. To ascertain cerebral blood flow (CBF) and metabolic correlates, 7-d postnatal rats were subjected to hypoxia-ischemia during which they were rendered either hypo-(3.5 kPa), normo- (5.1 kPa), or hypercapnic (7.3 kPa) by the inhalation of either 0, 3, or 6% CO2, 8% O2, balance N2. CBF during hypoxia-ischemia was better preserved in the normo- and hypercapnic rat pups; these animals also exhibited a stimulation of cerebral glucose utilization. Brain glucose concentrations were higher and lactate lower in the normo- and hypercapnic animals, indicating that glucose was consumed oxidatively in these groups rather than by anaerobic glycolysis, as apparently occurred in the hypocapnic animals. ATP and phosphocreatine were better preserved in the normo- and hypercapnic rats compared with the hypocapnic animals. Cerebrospinal fluid glutamate, as a reflection of the brain extracellular fluid concentration, was lowest in the hypercapnic rats at 2 h of hypoxia-ischemia. The data indicate that during hypoxia-ischemia in the immature rat, CBF is better preserved during normo- and hypercapnia; the greater oxygen delivery promotes cerebral glucose utilization and oxidative metabolism for optimal maintenance of tissue high energy phosphate reserves. An inhibition of glutamate secretion into the synaptic cleft and its attenuation of N-methyl-D-aspartate receptor activation would further protect the hypercapnic animal from hypoxic-ischemic brain damage.
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PMID:Effect of carbon dioxide on cerebral metabolism during hypoxia-ischemia in the immature rat. 921 33

A unique method for simultaneously measuring interstitial (pHe) as well as intracellular (pHi) pH in the brains of lightly anesthetized rats is described. A 4-mm microdialysis probe was inserted acutely into the right frontal lobe in the center of the area sampled by a surface coil tuned for the collection of 31P-NMR spectra. 2-Deoxyglucose 6-phosphate (2-DG-6-P) was microdialyzed into the rat until a single NMR peak was detected in the phosphomonoester region of the 31P spectrum. pHe and pHi values were calculated from the chemical shift of 2-DG-6-P and inorganic phosphate, respectively, relative to the phosphocreatine peak. The average in vivo pHe was 7.24+/-0.01, whereas the average pHi was 7.05+/-0.01 (n = 7). The average pHe value and the average CSF bicarbonate value (23.5+/-0.1 mEq/L) were used to calculate an interstitial Pco2 of 55 mm Hg. Rats were then subjected to a 15-min period of either hypercapnia, by addition of CO2 (2.5, 5, or 10%) to the ventilator gases, or hypocapnia (PCO2 < 30 mm Hg), by increasing the ventilation rate and volume. pHe responded inversely to arterial Pco2 and was well described (r2 = 0.91) by the Henderson-Hasselbalch equation, assuming a pKa for the bicarbonate buffer system of 6.1 and a solubility coefficient for CO2 of 0.031. This confirms the view that the bicarbonate buffer system is dominant in the interstitial space. pHi responded inversely and linearly to arterial PCO2. The intracellular effect was muted as compared with pHe (slope = -0.0025, r2 = 0.60). pHe and pHi values were also monitored during the first 12 min of ischemia produced by cardiac arrest. pHe decreases more rapidly than pHi during the first 5 min of ischemia. After 12 min of ischemia, pHe and pHi values were not significantly different (6.44+/-0.02 and 6.44+/-0.03, respectively). The limitations, advantages, and future uses of the combined microdialysis/31P-NMR method for measurement of pHe and pHi are discussed.
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PMID:In vivo microdialysis of 2-deoxyglucose 6-phosphate into brain: a novel method for the measurement of interstitial pH using 31P-NMR. 988 94

Previous studies have shown that severe hypocapnic ventilation [arterial carbon dioxide partial pressure (PaCO(2)) 7-10 mm Hg] in newborn animals results in decreased cerebral blood flow and decreased tissue oxidative metabolism. The present study tests the hypothesis that moderate hypocapnic ventilation (PaCO(2) 20 mm Hg) will result in decreased cerebral oxidative metabolism and nuclear DNA fragmentation in the cerebral cortex of normoxemic newborn piglets. Studies were performed in 10 anesthetized newborn piglets. The animals were ventilated for 1 h to achieve a PaCO(2) of 20 mm Hg in the hypocapnic (H) group (n = 5) and a PaCO(2) of 40 mm Hg in the normocapnic, control (C) group (n = 5). Tissue oxidative metabolism, reflecting tissue oxygenation, was documented biochemically by measuring tissue ATP and phosphocreatine (PCr) levels. Cerebral cortical nuclei were purified, nuclear DNA was isolated, and DNA content was determined. DNA samples were separated, stained, and compared with a standard DNA ladder. Tissue PCr levels were significantly lower in the H group than the C group (2.32 +/- 0.66 versus 3.73 +/- 0.32 micromol/g brain, p < 0.05), but ATP levels were preserved. Unlike C samples, H samples displayed a smear pattern of small molecular weight fragments between 100 and 12,000 bp. The density of DNA fragments was eight times higher in the H group than the C group, and DNA fragmentation varied inversely with levels of PCr (r = 0.93). These data demonstrate that moderate hypocapnia of 1 h duration results in decreased oxidative metabolism that is associated with DNA fragmentation in the cerebral cortex of newborn piglets. We speculate that hypocapnia-induced hypoxia results in increased intranuclear Ca(2+) flux, which causes protease and endonuclease activation, DNA fragmentation, and periventricular leukomalacia in newborn infants.
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PMID:Effect of moderate hypocapnic ventilation on nuclear DNA fragmentation and energy metabolism in the cerebral cortex of newborn piglets. 1164 52

The present study tests the hypothesis that a PaCO(2) of 27 mmHg for 1 hr results in increased neuronal nuclear Ca(++)/calmodulin-dependent protein kinase IV (CaM kinase IV) activity, pro-apoptotic protein expression and DNA fragmentation in the cerebral cortex of newborn piglets. Hypocapnic (HC) and normocapnic newborn piglets were studied. Tissue levels of ATP and phosphocreatine (PCr) were lower in the HC group. CaM kinase IV activity and Bax protein density were higher in the HC group. Bcl-2 protein density was the same in both groups, resulting in an increased ratio of Bax/Bcl-2 in the HC group. Density of nuclear DNA fragments was greater in the HC group and varied inversely with ATP and PCr levels. We conclude that hypocapnia (PaCO(2) 27 mmHg) results in increased expression of pro-apoptotic proteins and fragmentation of nuclear DNA in newborn piglets.
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PMID:The effect of hypocapnia (PaCO2 27 mmHg) on CaM kinase IV activity, Bax/Bcl-2 protein expression and DNA fragmentation in the cerebral cortex of newborn piglets. 1462 22

Previous studies have shown that hypocapnia results in fragmentation of nuclear DNA in the cerebral cortex of newborn piglets. We tested the hypothesis that hypocapnia results in decreased ATP and phosphocreatine (PCr) levels and increased nuclear high-affinity Ca++-ATPase activity, intranuclear Ca++ flux, and CaM kinase IV activity in neuronal nuclei of piglets. Three groups of piglets were ventilated as either hypocapnic (a PaCO2 of 20 mm Hg), normocapnic (a PaCO2 of 40 mm Hg), or corrected hypocapnic (ventilated as hypocapnic but with CO2 added to maintain normocapnia) for 1 h. Tissue ATP levels were lower in the hypocapnic than in the normocapnic group. PCr levels were lower and 45Ca++-influx, Ca++-ATPase activity and CaM kinase IV activity were higher in hypocapnic than in normocapnic or corrected hypocapnic piglets. We conclude that hypocapnia alters nuclear membrane Ca++ flux mechanisms and may alter neuronal phosphorylation mechanisms in the cerebral cortex of piglets.
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PMID:The effect of moderate hypocapnic ventilation on nuclear Ca2+-ATPase activity, nuclear Ca2+ flux, and Ca2+/calmodulin kinase IV activity in the cerebral cortex of newborn piglets. 1509 43

Substantial controversy persists in the literature concerning the physiologic consequences hypocapnia, or low partial pressure of carbon dioxide (PaCO(2)). Invasive animal studies have demonstrated large pH increases (>0.25 U), phosphocreatine (PCr) decreases (>30%), and adenosine triphosphate (ATP) decreases (>10%) after hyperventilation (HV) (20 mm Hg PaCO(2)). However, using magnetic resonance spectroscopy, HV studies in awake humans have demonstrated only small pH changes ( approximately 0.05 U) and no changes in PCr or ATP. It remains important to ascertain whether this failure to detect PCr changes in human studies reflects a true absence of changes, or a limitation in data fidelity. The present study used a rapidly interleaved phosphorus-proton spectroscopy acquisition from large samples at high magnetic field (4 T), to measure pH, PCr, inorganic phosphate, beta-ATP, and lactate changes with high temporal and signal sensitivity. Five of six subjects had usable data. During 20 mins HV, PaCO(2) reached a minimum at 16 mins (17 mm Hg); however, the maximum pH change (+0.047) peaked earlier (14 mins). Maximal lactate increases were measured at 15 mins. By 10 mins, maximum changes were observed for PCr (-3.4%) and inorganic phosphate (+6.4%). No changes in beta-ATP were observed. The peak in pH, despite continued decreases in PaCO(2), suggests active buffering during HV. These data, and the small magnitude of early PCr and inorganic phosphate changes, do not support substantial energy compromise during HV. Other mitigating factors, such as anesthesia-induced deregulation of the cerebrovasculature, might have contributed to the exaggerated metabolic changes observed in previous animal investigations.
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PMID:Brain changes to hypocapnia using rapidly interleaved phosphorus-proton magnetic resonance spectroscopy at 4 T. 1689 47

The effects of controlled voluntary hyperventilation (Hyp) on phosphocreatine (PCr) kinetics and muscle deoxygenation were examined during moderate-intensity plantar flexion exercise. Male subjects (n = 7) performed trials consisting of 20-min rest, 6-min exercise, and 10-min recovery in control [Con; end-tidal Pco(2) (Pet(CO(2))) approximately 33 mmHg] and Hyp (Pet(CO(2)) approximately 17 mmHg) conditions. Phosphorus-31 magnetic resonance and near-infrared spectroscopy were used simultaneously to monitor intramuscular acid-base status, high-energy phosphates, and muscle oxygenation. Resting intracellular hydrogen ion concentration ([H(+)](i)) was lower (P < 0.05) in Hyp [90 nM (SD 3)] than Con [96 nM (SD 4)]; however, at end exercise, [H(+)](i) was greater (P < 0.05) in Hyp [128 nM (SD 19)] than Con [120 nM (SD 17)]. At rest, [PCr] was not different between Con [36 mM (SD 2)] and Hyp [36 mM (SD 1)]. The time constant (tau) of PCr breakdown during transition from rest to exercise was greater (P < 0.05) in Hyp [39 s (SD 22)] than Con [32 s (SD 22)], and the PCr amplitude was greater (P < 0.05) in Hyp [26% (SD 4)] than Con [22% (SD 6)]. The deoxyhemoglobin and/or deoxymyoglobin (HHb) tau was similar between Hyp [13 s (SD 8)] and Con [10 s (SD 3)]; however, the amplitude was increased (P < 0.05) in Hyp [40 arbitrary units (au) (SD 23)] compared with Con [26 au (SD 17)]. In conclusion, our results indicate that Hyp-induced hypocapnia enhanced substrate-level phosphorylation during moderate-intensity exercise. In addition, the increased amplitude of the HHb response suggests a reduced local muscle perfusion in Hyp compared with Con.
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PMID:Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise. 1721 29


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