phosphocreatine and Hypocapnia

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.

Topics: Adenosine Triphosphate; Adult; Brain; Female; Humans; Hydrogen-Ion Concentration; Hyperventilation; Hypocapnia; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Phosphorus; Protons

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.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Cell Nucleus; Cerebral Cortex; DNA; DNA Fragmentation; Electrophoresis, Agar Gel; Energy Metabolism; Hypocapnia; Phosphocreatine; Regional Blood Flow

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.

Topics: Adenosine Triphosphate; Anesthesia, Inhalation; Anesthetics; Animals; Blood Pressure; Brain; Carbon Dioxide; Cats; Cerebrovascular Circulation; Energy Metabolism; Ethers; Female; Halothane; Hypocapnia; Magnetic Resonance Spectroscopy; Male; Methyl Ethers; Phosphates; Phosphocreatine; Sevoflurane