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...

The cardiovascular system responds to hyperbaric hyperoxia (HBO2) with vasoconstriction, hypertension, bradycardia, and reduced cardiac output (CO). We tested the hypothesis that these responses are linked by a common mechanism-activation of the arterial baroreflex. Baroreflex function in HBO2 was assessed in anesthetized and conscious rats after deafferentation of aortic or carotid baroreceptors or both. Cardiovascular and autonomic responses to HBO2 in these animals were compared with those in intact animals at 2.5 ATA for conscious rats and at 3 ATA for anesthetized rats. During O2 compression, hypertension was greater after aortic or carotid baroreceptor deafferentation and was significantly more severe if these procedures were combined. Similarly, the hyperoxic bradycardia observed in intact animals was diminished after aortic or carotid baroreceptor deafferentation and replaced by a slight tachycardia after complete baroreceptor deafferentation. We found that hypertension, bradycardia, and reduced CO--the initial cardiovascular responses to moderate levels of HBO2--are coordinated through a baroreflex-mediated mechanism initiated by HBO2-induced vasoconstriction. Furthermore, we have shown that baroreceptor activation in HBO2 inhibits sympathetic outflow and can partially reverse an O2-dependent increase in arterial pressure.

The hypothesis that decreases in brain blood flow during respiration of hyperbaric oxygen result from inactivation of nitric oxide (NO) by superoxide anions (O2(-)) is proposed. Changes in brain blood flow were assessed in conscious rats during respiration of atmospheric air or oxygen at a pressure of 4 atm after dismutation of O2(-) with superoxide dismutase or suppression of NO synthesis with the NO synthase inhibitor L-NAME. I.v. administration of superoxide dismutase increased brain blood flow in rats breathing air but was ineffective after previous inhibition of NO synthase. Hyperbaric oxygenation at 4 atm induced decreases in brain blood flow, though prior superoxide dismutase prevented hyperoxic vasoconstriction and increased brain blood flow in rats breathing hyperbaric oxygen. The vasodilatory effect of superoxide dismutase in hyperbaric oxygenation was not seen in animals given prior doses of the NO synthase inhibitor. These results provide evidence that one mechanism for hyperoxic vasoconstriction in the brain consists of inactivation of NO by superoxide anions, decreasing its basal vasorelaxing action.

In hyperbaric oxygen (HBO(2)) at or above 3 atmospheres absolute (ATA), autonomic pathways link central nervous system (CNS) oxygen toxicity to pulmonary damage, possibly through a paradoxical and poorly characterized relationship between central nitric oxide production and sympathetic outflow. To investigate this possibility, we assessed sympathetic discharges, catecholamine release, cardiopulmonary hemodynamics, and lung damage in rats exposed to oxygen at 5 or 6 ATA. Before HBO(2) exposure, either a selective inhibitor of neuronal nitric oxide synthase (NOS) or a nonselective NOS inhibitor was injected directly into the cerebral ventricles to minimize effects on the lung, heart, and peripheral circulation. Experiments were performed on both anesthetized and conscious rats to differentiate responses to HBO(2) from the effects of anesthesia. EEG spikes, markers of CNS toxicity in anesthetized animals, were approximately four times as likely to develop in control rats than in animals with central NOS inhibition. In inhibitor-treated animals, autonomic discharges, cardiovascular pressures, catecholamine release, and cerebral blood flow all remained below baseline throughout exposure to HBO(2). In control animals, however, initial declines in these parameters were followed by significant increases above their baselines. In awake animals, central NOS inhibition significantly decreased the incidence of clonic-tonic convulsions or delayed their onset, compared with controls. The novel findings of this study are that NO produced by nNOS in the periventricular regions of the brain plays a critical role in the events leading to both CNS toxicity in HBO(2) and to the associated sympathetic hyperactivation involved in pulmonary injury.

The physiological role of extracellular superoxide dismutase (SOD3) has received insufficient study. We investigated the hypothesis that SOD3, which neutralizes superoxide anions (O2(-)) in the intercellular space of the brain, prevents the inactivation of nitric oxide (NO) and is thus involved in regulating cerebral vascular tone. Local brain blood flow was measured in the striatum of anesthetized rats during administration of various combinations of a SOD mimetic, a SOD inhibitor, an NO donor, and an NOS inhibitor into the striatum using a Hamilton syringe. In normal conditions, SOD3 was found to minimize O2(-) levels, protecting endogenously produced NO at a sufficient level to maintain cerebral vascular tone and reactivity. SOD3 was found to increase the vasodilatory effect of endogenously produced NO in the brain. SOD3 was found to neutralize superoxide anions produced in the brain during respiration of 100% O2 and to maintain basal NO levels and its vasodilatory potential in normobaric hyperoxia.