Brain Changes to Hypocapnia Using Rapidly Interleaved Phosphorus-Proton Magnetic Resonance Spectroscopy at 4 T

Abstract

Substantial controversy persists in the literature concerning the physiologic consequences hypocapnia, or low partial pressure of carbon dioxide (PaCO2). 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 PaCO2). However, using magnetic resonance spectroscopy, HV studies in awake humans have demonstrated only small pH changes (∼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, β-ATP, and lactate changes with high temporal and signal sensitivity. Five of six subjects had usable data. During 20 mins HV, PaCO2 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 β-ATP were observed. The peak in pH, despite continued decreases in PaCO2, 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.