Hypercapnic cerebral vascular reactivity is decreased, in humans, during sleep compared with wakefulness

2003 ◽  
Vol 94 (6) ◽  
pp. 2197-2202 ◽  
Author(s):  
Guy E. Meadows ◽  
Helen M. A. Dunroy ◽  
Mary J. Morrell ◽  
Douglas R. Corfield
Keyword(s):  
Blood Flow ◽  
Vascular Reactivity ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Stage Iii ◽  
Left Middle Cerebral Artery ◽  
Cortical Blood Flow ◽  
Pulsed Doppler Ultrasound ◽  
End Tidal ◽  
Cerebral Vascular

During wakefulness, increases in the partial pressure of arterial CO2 result in marked rises in cortical blood flow. However, during stage III–IV, non-rapid eye movement (NREM) sleep, and despite a relative state of hypercapnia, cortical blood flow is reduced compared with wakefulness. In the present study, we tested the hypothesis that, in normal subjects, hypercapnic cerebral vascular reactivity is decreased during stage III–IV NREM sleep compared with wakefulness. A 2-MHz pulsed Doppler ultrasound system was used to measure the left middle cerebral artery velocity (MCAV; cm/s) in 12 healthy individuals while awake and during stage III–IV NREM sleep. The end-tidal Pco 2(Pet CO2 ) was elevated during the awake and sleep states by regulating the inspired CO2 load. The cerebral vascular reactivity to CO2 was calculated from the relationship between Pet CO2 and MCAV by using linear regression. From wakefulness to sleep, the Pet CO2 increased by 3.4 Torr ( P < 0.001) and the MCAV fell by 11.7% ( P < 0.001). A marked decrease in cerebral vascular reactivity was noted in all subjects, with an average fall of 70.1% ( P = 0.001). This decrease in hypercapnic cerebral vascular reactivity may, at least in part, explain the stage III–IV NREM sleep-related reduction in cortical blood flow.

Cerebral blood flow response to isocapnic hypoxia during slow-wave sleep and wakefulness

2004 ◽  
Vol 97 (4) ◽  
pp. 1343-1348 ◽  
Author(s):  
Guy E. Meadows ◽  
Denise M. O'Driscoll ◽  
Anita K. Simonds ◽  
Mary J. Morrell ◽  
Douglas R. Corfield
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vascular Reactivity ◽  
Slow Wave Sleep ◽  
Transcranial Doppler Ultrasound ◽  
Nrem Sleep ◽  
Left Middle Cerebral Artery ◽  
Arterial Blood ◽  
State Dependent ◽  
Cerebral Vascular

Nocturnal hypoxia is a major pathological factor associated with cardiorespiratory disease. During wakefulness, a decrease in arterial O2 tension results in a decrease in cerebral vascular tone and a consequent increase in cerebral blood flow; however, the cerebral vascular response to hypoxia during sleep is unknown. In the present study, we determined the cerebral vascular reactivity to isocapnic hypoxia during wakefulness and during stage 3/4 non-rapid eye movement (NREM) sleep. In 13 healthy individuals, left middle cerebral artery velocity (MCAV) was measured with the use of transcranial Doppler ultrasound as an index of cerebral blood flow. During wakefulness, in response to isocapnic hypoxia (arterial O2 saturation −10%), the mean (±SE) MCAV increased by 12.9 ± 2.2% ( P < 0.001); during NREM sleep, isocapnic hypoxia was associated with a −7.4 ± 1.6% reduction in MCAV ( P < 0.001). Mean arterial blood pressure was unaffected by isocapnic hypoxia ( P > 0.05); R-R interval decreased similarly in response to isocapnic hypoxia during wakefulness (−21.9 ± 10.4%; P < 0.001) and sleep (−20.5 ± 8.5%; P < 0.001). The failure of the cerebral vasculature to react to hypoxia during sleep suggests a major state-dependent vulnerability associated with the control of the cerebral circulation and may contribute to the pathophysiologies of stroke and sleep apnea.

Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation

1983 ◽  
Vol 55 (3) ◽  
pp. 813-822 ◽  
Author(s):  
J. B. Skatrud ◽  
J. A. Dempsey
Keyword(s):  
Periodic Breathing ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Positive Pressure ◽  
Sleep State ◽  
Co2 Partial Pressure ◽  
Apnea Duration ◽  
O2 Concentration ◽  
End Tidal ◽  
End Tidal Co2

The effect of sleep state on ventilatory rhythmicity following graded hypocapnia was determined in two normal subjects and one patient with a chronic tracheostomy. Passive positive-pressure hyperventilation (PHV) was performed for 3 min awake and during nonrapid-eye-movement (NREM) sleep with hyperoxia [fractional inspired O2 concentration (FIO2) = 0.50], normoxia and hypoxia (FIO2 = 0.12). During wakefulness, no immediate posthyperventilation apnea was noted following abrupt cessation of PHV in 27 of 28 trials [mean hyperventilation end-tidal CO2 partial pressure (PETCO2) 29 +/- 2 Torr, range 22-35]. During spontaneous breathing in hyperoxia, PETCO2 rose from 40.4 +/- 0.7 Torr awake to 43.2 +/- 1.4 Torr during NREM sleep. PHV during NREM sleep caused apnea when PETCO2 was reduced to 3-6 Torr below NREM sleep levels and 1-2 Torr below the waking level. In hypoxia, PETCO2 increased from 37.1 +/- 0.1 awake to 39.8 +/- 0.1 Torr during NREM sleep. PHV caused apnea when PETCO2 was reduced to levels 1-2 Torr below NREM sleep levels and 1-2 Torr above awake levels. Apnea duration (5-45 s) was significantly correlated to the magnitude of hypocapnia (range 27-41 Torr). PHV caused no apnea when isocapnia was maintained via increased inspired CO2. Prolonged hypoxia caused periodic breathing, and the abrupt transition from short-term hypoxic-induced hyperventilation to acute hyperoxia caused apnea during NREM sleep when PETCO2 was lowered to or below the subject's apneic threshold as predetermined (passively) by PHV. We concluded that effective ventilatory rhythmogenesis in the absence of stimuli associated with wakefulness is critically dependent on chemoreceptor stimulation secondary to PCO2-[H+].

Determinants of poststimulus potentiation in humans during NREM sleep

1992 ◽  
Vol 73 (5) ◽  
pp. 1958-1971 ◽  
Author(s):  
M. S. Badr ◽  
J. B. Skatrud ◽  
J. A. Dempsey
Keyword(s):  
Eye Movement ◽  
Control Period ◽  
Periodic Breathing ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Central Apnea ◽  
Inhibitory Effects ◽  
Arterial Pco2 ◽  
End Tidal ◽  
Sustained Hypoxia

To test whether active hyperventilation activates the “afterdischarge” mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.

scholarly journals Effect of Middle Cerebral Artery Compression on Pial Artery Pressure, Blood Flow, and Electrophysiological Function of Cerebral Cortex of Cat

1984 ◽  
Vol 4 (4) ◽  
pp. 593-598 ◽  
Author(s):  
H. Date ◽  
K.-A. Hossmann ◽  
T. Shima
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Experimental Situation ◽  
Vascular Occlusion ◽  
Left Middle Cerebral Artery ◽  
Cortical Blood Flow ◽  
Artery Pressure ◽  
Pial Artery ◽  
Left Middle

In 20 cats, the left middle cerebral artery was gradually compressed with a microdriven vascular occluder implanted by a transorbital approach. Pial artery pressure, cortical blood flow, segmental vascular resistance, electrocorticogram, and cortical steady potentials were measured in the territory of the left middle cerebral artery and correlated with the degree of vascular stenosis. Pial artery pressure began to decrease when the lumen of the middle cerebral artery was reduced to 200 μm. Cortical blood flow and EEG power declined when pial artery pressure fell below 35–40 mm Hg; cortical steady potential started to shift toward negativity at a pressure below 25–30 mm Hg; and both hemodynamic and electrophysiological changes were maximal at a pressure below 10 mm Hg. When the vascular occlusion was released within 5 min after the onset of ischemia, a pial artery pressure of only 18 mm Hg was necessary to restore normal blood flow. After 1-h occlusion, normalization of flow occurred at a pressure of 30 mm Hg. Since this pressure is still substantially below normal pial artery pressure, no-reflow does not seem to be of significance in this experimental situation.

scholarly journals Comparison of Cerebral Vascular Reactivity Measures Obtained Using Breath-Holding and CO2 Inhalation

2013 ◽  
Vol 33 (7) ◽  
pp. 1066-1074 ◽  
Author(s):  
Felipe B Tancredi ◽  
Richard D Hoge
Keyword(s):  
Arterial Spin Labeling ◽  
Vascular Reactivity ◽  
Automated System ◽  
Breath Holding ◽  
Breath Hold ◽  
Cerebral Vasculature ◽  
Fixed Concentration ◽  
Physiologic Modeling ◽  
End Tidal ◽  
Cerebral Vascular

Stimulation of cerebral vasculature using hypercapnia has been widely used to study cerebral vascular reactivity (CVR), which can be expressed as the quantitative change in cerebral blood flow (CBF) per mm Hg change in end-tidal partial pressure of CO2 (PETCO2). We investigate whether different respiratory manipulations, with arterial spin labeling used to measure CBF, lead to consistent measures of CVR. The approaches included: (1) an automated system delivering variable concentrations of inspired CO2 for prospective targeting of PETCO2, (2) administration of a fixed concentration of CO2 leading to subject-dependent changes in PETCO2, (3) a breath-hold (BH) paradigm with physiologic modeling of CO2 accumulation, and (4) a maneuver combining breath-hold and hyperventilation. When CVR was expressed as the percent change in CBF per mm Hg change in PETCO2, methods 1 to 3 gave consistent results. The CVR values using method 4 were significantly lower. When CVR was expressed in terms of the absolute change in CBF (mL/100g per minute per mm Hg), greater discrepancies became apparent: methods 2 and 3 gave lower absolute CVR values compared with method 1, and the value obtained with method 4 was dramatically lower. Our findings indicate that care must be taken to ensure that CVR is measured over the linear range of the CBF-CO2 dose-response curve, avoiding hypocapnic conditions.

scholarly journals Evaluation of the cerebral hemodynamic response to rhythmic handgrip

2000 ◽  
Vol 88 (6) ◽  
pp. 2205-2213 ◽  
Author(s):  
Cole A. Giller ◽  
Angela M. Giller ◽  
Christopher R. Cooper ◽  
Mustapha R. Hatab
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Transcranial Doppler Ultrasound ◽  
Normal Subjects ◽  
Flow Index ◽  
Luminal Area ◽  
End Tidal ◽  
Exercise Environment ◽  
Artery Flow

The response of the cerebral circulation to exercise has been studied with transcranial Doppler ultrasound (TCD) because this modality provides continuous measurements of blood velocity and is well suited for the exercise environment. The use of TCD as an index of cerebral blood flow, however, requires the assumption that the diameter of the insonated vessel is constant. Here, we examine this assumption for rhythmic handgrip using a spectral index designed to measure trends in vessel flow. Nineteen normal subjects were studied during 5 min of volitional maximum rhythmic right handgrip at 1 Hz. TCD velocities from both middle arteries (left and right), blood pressure, and end-tidal Pco 2 were recorded every 10 s. A spectral weighted sum was also calculated as a flow index (FI). Averages were computed from the last 2 min of handgrip. Relative changes in velocity, FI, and pressure were calculated. The validity of FI was tested by comparing the change in diameter derived from equations relating flow and diameter. Mean blood pressure increased 23.8 ± 17.8% (SD), and velocity increased 13.3 ± 9.8% (left) and 9.6 ± 8.3% (right). Although the mean change in FI was small [2.0 ± 18.2% (left) and 4.7 ± 29.7% (right)], the variation was high: some subjects showed a significant increase in FI and others a significant decrease. Diameter estimates from two equations relating flow and luminal area were not significantly different. Decreases in FI were associated with estimated diameter decreases of 10%. Our data suggest that the cerebral blood flow (CBF) response to rhythmic handgrip is heterogeneous and that middle cerebral artery flow can decrease in some subjects, in agreement with prior studies using the Kety-Schmidt technique. We speculate that the velocity increase is due to sympathetically mediated vasoconstriction rather than a ubiquitous flow increase. Our data suggest that the use of ordinary TCD velocities to interpret the CBF response during exercise may be invalid.

scholarly journals Measuring Cerebrovascular Reactivity: Sixteen Avoidable Pitfalls

2021 ◽  
Vol 12 ◽  
Author(s):  
Olivia Sobczyk ◽  
Jorn Fierstra ◽  
Lakshmikumar Venkatraghavan ◽  
Julien Poublanc ◽  
James Duffin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Reactivity ◽  
Relevant Information ◽  
Blood Oxygen Level Dependent ◽  
Lessons Learned ◽  
Cerebrovascular Reactivity ◽  
Vascular Pathology ◽  
Blood Oxygen Level ◽  
Vasoactive Agent ◽  
Cerebral Vascular

An increase in arterial PCO2 is the most common stressor used to increase cerebral blood flow for assessing cerebral vascular reactivity (CVR). That CO2 is readily obtained, inexpensive, easy to administer, and safe to inhale belies the difficulties in extracting scientifically and clinically relevant information from the resulting flow responses. Over the past two decades, we have studied more than 2,000 individuals, most with cervical and cerebral vascular pathology using CO2 as the vasoactive agent and blood oxygen-level-dependent magnetic resonance imaging signal as the flow surrogate. The ability to deliver different forms of precise hypercapnic stimuli enabled systematic exploration of the blood flow-related signal changes. We learned the effect on CVR of particular aspects of the stimulus such as the arterial partial pressure of oxygen, the baseline PCO2, and the magnitude, rate, and pattern of its change. Similarly, we learned to interpret aspects of the flow response such as its magnitude, and the speed and direction of change. Finally, we were able to test whether the response falls into a normal range. Here, we present a review of our accumulated insight as 16 “lessons learned.” We hope many of these insights are sufficiently general to apply to a range of types of CO2-based vasoactive stimuli and perfusion metrics used for CVR.

scholarly journals Influence of cerebral blood flow on breathing stability

2009 ◽  
Vol 106 (3) ◽  
pp. 850-856 ◽  
Author(s):  
Ailiang Xie ◽  
James B. Skatrud ◽  
Steven R. Barczi ◽  
Kevin Reichmuth ◽  
Barbara J. Morgan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Pressure Support ◽  
Central Sleep Apnea ◽  
Random Order ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Cerebrovascular Reactivity ◽  
The Difference ◽  
Apnea Threshold

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in PaCO2 in congestive heart failure patients with central sleep apnea compared with those without apnea. Since the regulation of CBF serves to minimize oscillations in H+ and Pco2 at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in PaCO2 would narrow the difference between the eupneic PaCO2 and the apneic threshold PaCO2 (ΔPaCO2), known as the CO2 reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO2 by ∼25% below control. The CO2 reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mode to gradually reduce PaCO2 until apnea occurred. results: Indo significantly reduced the CO2 reserve required to produce apnea from 6.3 ± 0.5 to 4.4 ± 0.7 mmHg ( P = 0.01) and increased the slope of the ventilation decrease in response to hypocapnic inhibition below eupnea (control vs. Indo: 1.06 ± 0.10 vs. 1.61 ± 0.27 l·min−1·mmHg−1, P < 0.05). We conclude that reductions in the normal cerebral vascular response to hypocapnia will increase the susceptibility to apneas and breathing instability during sleep.

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