Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans

Andrew P. Binks, Vincent J. Cunningham, Lewis Adams, Robert B. Banzett
2008 Journal of applied physiology  
Binks AP, Cunningham VJ, Adams L, Banzett RB. Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans. Hypoxia increases cerebral blood flow (CBF), but it is unknown whether this increase is uniform across all brain regions. We used H 2 15 O positron emission tomography imaging to measure absolute blood flow in 50 regions of interest across the human brain (n ϭ 5) during normoxia and moderate hypoxia. PCO 2 was kept constant (ϳ44 Torr) throughout the
more » ... dy to avoid decreases in CBF associated with the hypocapnia that normally occurs with hypoxia. Breathing was controlled by mechanical ventilation. During hypoxia (inspired PO 2 ϭ 70 Torr), mean end-tidal PO 2 fell to 45 Ϯ 6.3 Torr (means Ϯ SD). Mean global CBF increased from normoxic levels of 0.39 Ϯ 0.13 to 0.45 Ϯ 0.13 ml/g during hypoxia. Increases in regional CBF were not uniform and ranged from 9.9 Ϯ 8.6% in the occipital lobe to 28.9 Ϯ 10.3% in the nucleus accumbens. Regions of interest that were better perfused during normoxia generally showed a greater regional CBF response. Phylogenetically older regions of the brain tended to show larger vascular responses to hypoxia than evolutionary younger regions, e.g., the putamen, brain stem, thalamus, caudate nucleus, nucleus accumbens, and pallidum received greater than average increases in blood flow, while cortical regions generally received below average increases. The heterogeneous blood flow distribution during hypoxia may serve to protect regions of the brain with essential homeostatic roles. This may be relevant to conditions such as altitude, breath-hold diving, and obstructive sleep apnea, and may have implications for functional brain imaging studies that involve hypoxia. stroke; altitude; obstructive sleep apnea THE GLOBAL RESPONSE OF THE cerebral vasculature to changes in arterial oxygen tension has previously been described (3, 5, 7, 24) . Cerebral blood flow (CBF) increases as arterial saturation of oxygen (Sa O 2 ) falls (5, 7, 23). While there are numerous papers describing the global response of CBF to hypoxia, there is little information on the regional distribution of CBF during hypoxia; the information that does exist is confounded by simultaneous PCO 2 changes. We hypothesize that there would be significant differences among brain regions in the blood flow response to hypoxia in the absence of changes in PCO 2 . The most common experimental intervention to produce cerebral hypoxia is exposure to low inspired PO 2 without control of other variables. In such experiments, subjects have been allowed to breathe spontaneously during the intervention, and as a consequence the reflex increase in alveolar ventilation also markedly reduced arterial PCO 2 (Pa CO 2 ). Low Pa CO 2 re-duces CBF, thereby opposing the effect of low PO 2 on CBF (10, 38). Outside the laboratory, a similar situation exists at high altitude. In contrast, when cerebral hypoxia is produced by respiratory disease, asphyxia, or ischemia, the PCO 2 is generally normal or elevated. Here we held Pa CO 2 constant during hypoxia and used H 2 15 O positron emission tomography (PET) to image the CBF response. It is not known whether the vascular response to hypoxia is uniform across the brain: some evidence suggests that the response to hypoxia is uniform (33); other evidence using autoradiography (45), video microscopy (17) , MRI (36), and PET (4, 20) suggests that some brain regions receive a greater CBF increase. Nonuniform flow responses could be important in situations such as altitude and breath-hold diving and in clinical situations such as sleep apnea; more responsive regions may be better protected during these hypoxic episodes. The present study used H 2 15 O PET to measure regional cerebral blood flow (rCBF) in five healthy men during hypoxia with constant Pa CO 2 . The concentration of radioactivity in arterial blood was measured continuously throughout the PET scans to provide an input function that allows quantitative estimates of absolute blood flow to be obtained. We measured rCBF during periods of moderate hypoxia (Sa O 2 ϭ 80%) and periods of normoxia (Sa O 2 ϭ 97%). Pa CO 2 was maintained constant throughout the study by controlling ventilation and inspired PCO 2 . Mean regional blood flow responses for 50 functional regions of interest (ROIs) are reported, and the data revealed that there is a nonuniform vascular response to normocapnic hypoxia in humans. Six subjects, all men and all righthanded, gave informed consent. Before the brain imaging study, subjects practiced the protocol in the laboratory so that they were familiar with the procedures, and we could ensure that they were appropriate candidates (i.e., there were no ECG abnormalities during hypoxia). One normal, healthy subject was excluded from the study after cardiac arrhythmias were noted during exposure to hypoxia in a practice session (a normal heart rhythm returned when normoxia was restored). We were unable to replace the excluded subject due to logistical constraints. Physiological measurements. Tidal volume (VT) and respiratory frequency were controlled by mechanical ventilation (Siemens 900B in volume control mode) via a mouthpiece at an initial minute
doi:10.1152/japplphysiol.00069.2007 pmid:17991793 fatcat:2yj55qeuovftpg7zgbusvexrqm