Cerebral Blood Flow and Brain Oxygenation in Rats Breathing Oxygen under Pressure

Abstract

Hyperbaric oxygen (HBO 2 ) increases oxygen tension (PO 2 ) in blood but reduces blood flow by means of O 2 -induced vasoconstriction. Here we report the first quantitative evaluation of these opposing effects on tissue PO 2 in brain, using anesthetized rats exposed to HBO 2 at 2 to 6 atmospheres absolute (ATA). We assessed the contribution of regional cerebral blood flow (rCBF) to brain PO 2 as inspired PO 2 (PiO 2 ) exceeds 1 ATA. We measured rCBF and local PO 2 simultaneously in striatum using collocated platinum electrodes. Cerebral blood flow was computed from H 2 clearance curves in vivo and PO 2 from electrodes calibrated in vitro, before and after insertion. Arterial PCO 2 was controlled, and body temperature, blood pressure, and EEG were monitored. Scatter plots of rCBF versus PO 2 were nonlinear (R 2 ¼ 0.75) for rats breathing room air but nearly linear (R 2 ¼ 0.88-0.91) for O 2 at 2 to 6 ATA. The contribution of rCBF to brain PO 2 was estimated at constant inspired PO 2 , by increasing rCBF with acetazolamide (AZA) or decreasing it with N-nitro-L-arginine methyl ester (L-NAME). At basal rCBF (78 mL/100 g min), local PO 2 increased 7-to 33-fold at 2 to 6 ATA, compared with room air. A doubling of rCBF increased striatal PO 2 not quite two-fold in rats breathing room air but 13-to 64-fold in those breathing HBO 2 at 2 to 6 ATA. These findings support our hypothesis that HBO 2 increases PO 2 in brain in direct proportion to rCBF. IntroductionThe O 2 content of blood is the mathematical product of hemoglobin concentration and arterial hemoglobin O 2 saturation, the latter being a nonlinear function of arterial oxygen partial pressure (PaO 2 ). The small amount of O 2 dissolved in plasma is usually negligible. However, breathing hyperbaric oxygen (HBO 2 ), that is oxygen at pressures greater than 1 atmosphere absolute (ATA), raises PaO 2 beyond the point at which hemoglobin is fully saturated, so that the dissolved fraction becomes the main source of O 2 available to cells. But this does not assure enhanced O 2 delivery to brain, because tissue PO 2 also depends on regional blood flow.Tissue oxygen tension (PO 2 ) is a dynamic balance between O 2 delivery and consumption. Many authors have reported increased brain PO 2 in HBO 2 (Jamieson and Van Den Brenk, 1962;Bennett, 1965;Bean et al, 1971;Torbati et al, 1978;Hunt et al, 1978), and reviews are available (Jamieson, 1989;Camporesi et al, 1996;Dean et al, 2003). It is also known that total or regional cerebral blood flow (rCBF) decreases in HBO 2 as a function of pressure and time. But the contribution of CBF to brain PO 2 had never been quantified. Cerebral vasoconstriction and decreased total or rCBF have been shown in healthy volunteers and patients breathing O 2 at 3.5 ATA for brief periods (Lambertsen et al, 1953;Visser et al, 1996;Omae et al, 1998). In animals, in which HBO 2 is maintained for longer times and at higher pressures, the rCBF response is biphasic: the initial decrease in rCBF is followed by a secondary rise to www.jcbfm.com control leve...

Neurovascular Coupling in Rat Brain Operates Independent of Hemoglobin Deoxygenation

“…As shown by Demchenko et al (2005), tissue pO 2 values of above 400 mm Hg were reached already at 3 ATA when hyperoxygenation-induced decrease of resting CBF was prevented by acetazolamide application, which slightly elevated the arterial pCO 2 up to 44 mm Hg. In this study, owing to spontaneous breathing in the hyperbaric chamber, arterial pCO 2 and resting CBF were increased to values comparable with those achieved by Demchenko et al, (2005), suggesting an equally elevated tissue pO 2 of > 400 mm Hg. This increase in tissue O 2 leads to a complete oxidation of cytochrome oxidase type aa3 (Hempel et al, 1977) and of mitochondrial NADH (Meirovithz et al, 2007).…”

“…At partial pressures > 3 ATA, brain concentrations of oxygenated hemoglobin and thus microcirculatory hemoglobin saturation reach a maximum (Meirovithz et al, 2007), the amount of physically dissolved oxygen significantly increases up to 7 mL/100 mL blood, and tissue pO 2 in the brain increases to more than 400 mm Hg (Demchenko et al, 2005;Jamieson and Van den Brenk, 1962). As shown by Demchenko et al (2005), tissue pO 2 values of above 400 mm Hg were reached already at 3 ATA when hyperoxygenation-induced decrease of resting CBF was prevented by acetazolamide application, which slightly elevated the arterial pCO 2 up to 44 mm Hg. In this study, owing to spontaneous breathing in the hyperbaric chamber, arterial pCO 2 and resting CBF were increased to values comparable with those achieved by Demchenko et al, (2005), suggesting an equally elevated tissue pO 2 of > 400 mm Hg.…”

Optical coherence tomography for the quantitative study of cerebrovascular physiology

“…A breathing mixture of 20% O 2 and 80% N 2 was used. A platinum electrode for hydrogen clearance with a diameter of 100 mm, sampling from a calculated tissue volume of 0.58 mm 3 , was used (Demchenko et al, 2005). The electrode was inserted to 1 mm depth (Feng et al, 1988) into the cortex.…”

Transient Hypoxia Stimulates Mitochondrial Biogenesis in Brain Subcortex by a Neuronal Nitric Oxide Synthase-Dependent Mechanism

“…Brain PO 2 measurements were conducted in Wt and NOS-deficient strains ventilated with room air, 8% O 2 (balance N 2 ), and room air after hypoxia. The electrodes were used also for regional cerebral blood flow (rCBF) measurements using hydrogen clearance (Demchenko et al, 2005).…”