We assessed the validity of recording blood flow in the superior sagittal sinus (Qss) as a measure of cerebral blood flow (CBF). While anesthetized, 10 lambs were instrumented with a transit-time ultrasonic flow probe around the superior sagittal sinus to measure Qss, electrodes to assess sleep state, catheters to measure cerebral perfusion pressure (Pcp), and an occlusive cuff around the common brachiocephalic artery to vary blood pressure. After 72 h recovery, lambs were studied during spontaneous sleep-wake cycles to establish 1) the normal range of Qss and 2) the response rate of Qss to rapid alterations of Pcp. Subsequently, the lambs were reanesthetized, and the measurement of Qss was calibrated and validated. Qss was linearly related to the arterial inflow of 35% of the brain mass (y = 0.5 x + 1.6, r = 0.93, n = 4). Qss was greater in active sleep (154.1 +/- 45.7 ml.min-1 x 100 g-1, mean +/- SD, n = 5) than in quiet sleep (97.1 +/- 40.8 ml.min-1 x 100 g-1) and quiet wakefulness (107 +/- 44.3 ml.min-1 x 100 g-1, P < 0.05). Qss responded rapidly (within one beat) to spontaneous and to induced transient changes in Pcp. We conclude that recording blood flow in the superior sagittal sinus provides a simple, continuous, and quantitative measure of CBF from a defined area of the brain and is appropriate for studying transient changes in the cerebral circulation.

Little is known of the factors that regulate CBF in sleep. We therefore studied 10 lambs to assess the vasodilatory processes that underlie cerebral autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP), were rapidly made hypotensive by inflating a cuff around the brachiocephalic artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3, mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The time (seconds) required for maximal cerebral vasodilation to occur was longer in active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the changes in CPP induced with brachiocephalic occlusion were equal in each state. In conclusion, our studies provide the first evidence that the vasoactive mechanisms that underlie autoregulation of the cerebral circulation function during sleep. Moreover, our data reveal that the speed and the magnitude of the vasodilatory reserves available for autoregulation are significantly less in active sleep than in quiet sleep.

Nitric oxide (NO), being produced by active neurones and also being a cerebral vasodilator, may couple brain activity and blood flow in sleep, particularly during active sleep (AS), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (CBF) compared with quiet wakefulness (QW) and quiet sleep (QS). This study examined CBF and cerebral vascular resistance (CVR) in lambs (n = 6) during spontaneous sleep-wake cycles before and after infusion of N(omega)-nitro-L-arginine (L-NNA), an inhibitor of NO synthase. L-NNA infusion produced increases in CVR and decreases in CBF during all sleep-wake stages, with the greatest changes occurring in AS (DeltaCVR, 88 +/- 19%; DeltaCBF -24 +/- 8%). The characteristic CVR and CBF differences among AS, QS, and QW disappeared within 1-3 h of L-NNA infusion, but had reappeared by 24 h despite persisting cerebral vasoconstriction. These experiments show that NO promotes cerebral vasodilatation during sleep as well as wakefulness, particularly during AS. Additionally, NO is the major, although not sole, determinant of the CBF differences that exist between sleep-wake states.

As nitric oxide (NO) may be a particularly important vasodilator in early life, we investigated its role in the regulation of the gastrointestinal (GI) circulation at mid-gestation. Cardiac output and GI blood flow were measured by the radioactive microsphere technique in eight chronically instrumented and unanesthetized mid-gestation fetal sheep. Mean arterial pressure (MAP), heart rate, blood flow, oxygen delivery, and vascular resistance were determined before and after infusion of the specific NO synthase inhibitor, Nomega-nitro-L-arginine (L-NNA) at doses of 10 and 25 mg/kg. In response to L-NNA infusion, MAP increased (p < 0.01) and combined ventricular output decreased (p < 0.001). GI blood flow and oxygen delivery decreased and vascular resistance increased in the stomach and all segments of the small and large intestine (all p < 0.001). The greatest reduction in blood flow was in the small intestine (p < 0.01) and the basal differential pattern of small intestinal blood flow exceeding large intestinal flow was completely abolished. These changes were much greater than those previously described in late-gestation fetuses. Our results suggest that, at mid-gestation, NO plays a major role in the regulation of blood flow and vascular tone across all segments of the fetal GI tract, with its effects being more pronounced than later in development.