Cerebral Blood Flow Reactivity to Changes in Carbon Dioxide Calculated Using End-Tidal versus Arterial Tensions

We retrospectively examined arterial and endtidal estimations of CO2 tension used to calculate cerebrovascular reactivity in 68 anesthetized patients. CBF was measured using the intravenous 133Xe technique at mean ± SD Paco2 values of 28.2 ± 5.2 and 38.8 ± 4.8 mm Hg. The correlation between all Paco2 and end-tidal Pco2 (Petco2) values was y = 0.85 x −0.49 ( r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between Paco2 and Petco2 ( y = 0.11 x + 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g−1 min−1 mm Hg−1) was similar (p = 0.358) when calculated by using either Paco2 (1.9 ± 0.8) or Petco2 (1.8 ± 0.8) and highly correlated ( y = 0.86 x + 0.23; r = 0.91, p = 0.0001). The CBF response to changes in CO2 tension can be reliably estimated from noninvasive measurement of Petco2.

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Comparisons of the Nonlinear Relationship of Cerebral Blood Flow Response and Cerebral Vasomotor Reactivity to Carbon Dioxide under Hyperventilation between Postural Orthostatic Tachycardia Syndrome Patients and Healthy Subjects

Journal of Clinical Medicine ◽

10.3390/jcm9124088 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4088

Author(s):

Shyan-Lung Lin ◽

Shoou-Jeng Yeh ◽

Ching-Kun Chen ◽

Yu-Liang Hsu ◽

Chih-En Kuo ◽

...

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Blood Flow Velocity ◽

Cerebral Blood Flow Velocity ◽

Postural Orthostatic Tachycardia Syndrome ◽

Significant Difference ◽

Cerebral Vasomotor Reactivity ◽

End Tidal ◽

Fitting Model

Postural orthostatic tachycardia syndrome (POTS) typically occurs in youths, and early accurate POTS diagnosis is challenging. A recent hypothesis suggests that upright cognitive impairment in POTS occurs because reduced cerebral blood flow velocity (CBFV) and cerebrovascular response to carbon dioxide (CO2) are nonlinear during transient changes in end-tidal CO2 (PETCO2). This novel study aimed to reveal the interaction between cerebral autoregulation and ventilatory control in POTS patients by using tilt table and hyperventilation to alter the CO2 tension between 10 and 30 mmHg. The cerebral blood flow velocity (CBFV), partial pressure of end-tidal carbon dioxide (PETCO2), and other cardiopulmonary signals were recorded for POTS patients and two healthy groups including those aged >45 years (Healthy-Elder) and aged <45 years (Healthy-Youth) throughout the experiment. Two nonlinear regression functions, Models I and II, were applied to evaluate their CBFV-PETCO2 relationship and cerebral vasomotor reactivity (CVMR). Among the estimated parameters, the curve-fitting Model I for CBFV and CVMR responses to CO2 for POTS patients demonstrated an observable dissimilarity in CBFVmax (p = 0.011), mid-PETCO2 (p = 0.013), and PETCO2 range (p = 0.023) compared with those of Healthy-Youth and in CBFVmax (p = 0.015) and CVMRmax compared with those of Healthy-Elder. With curve-fitting Model II for POTS patients, the fit parameters of curvilinear (p = 0.036) and PETCO2 level (p = 0.033) displayed significant difference in comparison with Healthy-Youth parameters; range of change (p = 0.042), PETCO2 level, and CBFVmax also displayed a significant difference in comparison with Healthy-Elder parameters. The results of this study contribute toward developing an early accurate diagnosis of impaired CBFV responses to CO2 for POTS patients.

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The Clamping of End-Tidal Carbon Dioxide Does Not Influence Cognitive Function Performance During Moderate Hyperthermia With or Without Skin Temperature Manipulation

Frontiers in Psychology ◽

10.3389/fpsyg.2021.788027 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ricardo Schultz Martins ◽

Phillip J. Wallace ◽

Scott W. Steele ◽

Jake S. Scott ◽

Michael J. Taber ◽

...

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Cognitive Function ◽

Skin Temperature ◽

Core Temperature ◽

Cognitive Testing ◽

Cognitive Test ◽

End Tidal Carbon Dioxide ◽

End Tidal

Increases in body temperature from heat stress (i.e., hyperthermia) generally impairs cognitive function across a range of domains and complexities, but the relative contribution from skin versus core temperature changes remains unclear. Hyperthermia also elicits a hyperventilatory response that decreases the partial pressure of end-tidal carbon dioxide (PetCO2) and subsequently cerebral blood flow that may influence cognitive function. We studied the role of skin and core temperature along with PetCO2 on cognitive function across a range of domains. Eleven males completed a randomized, single-blinded protocol consisting of poikilocapnia (POIKI, no PetCO2 control) or isocapnia (ISO, PetCO2 maintained at baseline levels) during passive heating using a water-perfused suit (water temperature ~ 49°C) while middle cerebral artery velocity (MCAv) was measured continuously as an index of cerebral blood flow. Cognitive testing was completed at baseline, neutral core-hot skin (37.0 ± 0.2°C-37.4 ± 0.3°C), hot core-hot skin (38.6 ± 0.3°C-38.7 ± 0.2°C), and hot core-cooled skin (38.5 ± 0.3°C-34.7 ± 0.6°C). The cognitive test battery consisted of a detection task (psychomotor processing), 2-back task (working memory), set-shifting and Groton Maze Learning Task (executive function). At hot core-hot skin, poikilocapnia led to significant (both p < 0.05) decreases in PetCO2 (∆−21%) and MCAv (∆−26%) from baseline, while isocapnia clamped PetCO2 (∆ + 4% from baseline) leading to a significantly (p = 0.023) higher MCAv (∆−18% from baseline) compared to poikilocapnia. There were no significant differences in errors made on any task (all p > 0.05) irrespective of skin temperature or PetCO2 manipulation. We conclude that neither skin temperature nor PetCO2 maintenance significantly alter cognitive function during passive hyperthermia.

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The CO2 stimulus for cerebrovascular reactivity: Fixing inspired concentrations vs. targeting end-tidal partial pressures

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16639326 ◽

2016 ◽

Vol 36 (6) ◽

pp. 1004-1011 ◽

Cited By ~ 25

Author(s):

Joseph A Fisher

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Stimulus Change ◽

Cerebrovascular Reactivity ◽

Main Concern ◽

Precise Control ◽

Trade Offs ◽

Partial Pressures ◽

Response Change ◽

End Tidal

Cerebrovascular reactivity (CVR) studies have elucidated the physiology and pathophysiology of cerebral blood flow regulation. A non-invasive, high spatial resolution approach uses carbon dioxide (CO2) as the vasoactive stimulus and magnetic resonance techniques to estimate the cerebral blood flow response. CVR is assessed as the ratio response change to stimulus change. Precise control of the stimulus is sought to minimize CVR variability between tests, and show functional differences. Computerized methods targeting end-tidal CO2 partial pressures are precise, but expensive. Simpler, improvised methods that fix the inspired CO2 concentrations have been recommended as less expensive, and so more widely accessible. However, these methods have drawbacks that have not been previously presented by those that advocate their use, or those that employ them in their studies. As one of the developers of a computerized method, I provide my perspective on the trade-offs between these two methods. The main concern is that declaring the precision of fixed inspired concentration of CO2 is misleading: it does not, as implied, translate to precise control of the actual vasoactive stimulus – the arterial partial pressure of CO2. The inherent test-to-test, and therefore subject-to-subject variability, precludes clinical application of findings. Moreover, improvised methods imply widespread duplication of development, assembly time and costs, yet lack uniformity and quality control. A tabular comparison between approaches is provided.

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Cerebral blood flow modulation insufficiency in brain networks in multiple sclerosis: A hypercapnia MRI study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16654922 ◽

2016 ◽

Vol 36 (12) ◽

pp. 2087-2095 ◽

Cited By ~ 16

Author(s):

Olga Marshall ◽

Sanjeev Chawla ◽

Hanzhang Lu ◽

Louise Pape ◽

Yulin Ge

Keyword(s):

Multiple Sclerosis ◽

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Brain Networks ◽

Cerebrovascular Reactivity ◽

Functional Networks ◽

Attention Networks ◽

Default Mode ◽

Multiple Sclerosis Patients

Cerebrovascular reactivity measures vascular regulation of cerebral blood flow and is responsible for maintaining healthy neurovascular coupling. Multiple sclerosis exhibits progressive neurodegeneration and global cerebrovascular reactivity deficits. This study investigates varied degrees of cerebrovascular reactivity impairment in different brain networks, which may be an underlying cause for functional changes in the brain, affecting long-distance projection integrity and cognitive function; 28 multiple sclerosis and 28 control subjects underwent pseudocontinuous arterial spin labeling perfusion MRI to measure cerebral blood flow under normocapnia (room air) and hypercapnia (5% carbon dioxide gas mixture) breathing. Cerebrovascular reactivity, measured as normocapnic to hypercapnic cerebral blood flow percent increase normalized by end-tidal carbon dioxide change, was determined from seven functional networks (default mode, frontoparietal, somatomotor, visual, limbic, dorsal, and ventral attention networks). Group analysis showed significantly decreased cerebrovascular reactivity in patients compared to controls within the default mode, frontoparietal, somatomotor, and ventral attention networks after multiple comparison correction. Regression analysis showed a significant correlation of cerebrovascular reactivity with lesion load in the default mode and ventral attention networks and with gray matter atrophy in the default mode network. Functional networks in multiple sclerosis patients exhibit varied amounts of cerebrovascular reactivity deficits. Such blood flow regulation abnormalities may contribute to functional communication disruption in multiple sclerosis.

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Cerebral blood flow regulation in women across menstrual phase: differential contribution of cyclooxygenase to basal, hypoxic, and hypercapnic vascular tone

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00106.2016 ◽

2016 ◽

Vol 311 (2) ◽

pp. R222-R231 ◽

Cited By ~ 21

Author(s):

Garrett L. Peltonen ◽

John W. Harrell ◽

Benjamin P. Aleckson ◽

Kaylie M. LaPlante ◽

Meghan K. Crain ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Menstrual Cycle ◽

Transcranial Doppler Ultrasound ◽

Follicular Phase ◽

Cerebrovascular Reactivity ◽

Menstrual Phase ◽

Arterial Blood ◽

End Tidal ◽

Late Follicular Phase

In healthy young women, basal cerebral blood flow (CBF) and cerebrovascular reactivity may change across the menstrual cycle, but mechanisms remain untested. When compared with the early follicular phase of the menstrual cycle, we hypothesized women in late follicular phase would exhibit: 1) greater basal CBF, 2) greater hypercapnic increases in CBF, 3) greater hypoxic increases in CBF, and 4) increased cyclooxygenase (COX) signaling. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 11 healthy women (23 ± 1 yr) during rest, hypoxia, and hypercapnia. Subjects completed four visits: two during the early follicular (∼ day 3) and two during the late follicular (∼ day 14) phases of the menstrual cycle, with and without COX inhibition (oral indomethacin). Isocapnic hypoxia elicited an SPO2 = 90% and SPO2 = 80% for 5 min each. Separately, hypercapnia increased end-tidal CO2 10 mmHg above baseline. Cerebral vascular conductance index (CVCi = MCAv/MABP·100, where MABP is mean arterial blood pressure) was calculated and a positive change reflected vasodilation (ΔCVCi). Basal CVCi was greater in the late follicular phase ( P < 0.001). Indomethacin decreased basal CVCi (∼37%) and abolished the phase difference ( P < 0.001). Hypoxic ΔCVCi was similar between phases and unaffected by indomethacin. Hypercapnic ΔCVCi was similar between phases, and indomethacin decreased hypercapnic ΔCVCi (∼68%; P < 0.001) similarly between phases. In summary, while neither hypercapnic nor hypoxic vasodilation is altered by menstrual phase, increased basal CBF in the late follicular phase is fully explained by a greater contribution of COX. These data provide new mechanistic insight into anterior CBF regulation across menstrual phases and contribute to our understanding of CBF regulation in women.

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Cerebral blood flow response to hypercapnia in immature fetal sheep

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.261.5.h1366 ◽

1991 ◽

Vol 261 (5) ◽

pp. H1366-H1370 ◽

Cited By ~ 2

Author(s):

S. M. Helou ◽

M. L. Hudak ◽

M. D. Jones

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Axillary Artery ◽

Vena Cava ◽

In Utero ◽

Carbon Dioxide Tension ◽

Fetal Sheep ◽

Sagittal Sinus ◽

The Difference

We have reported recently that the cerebral blood flow (CBF) response to isocapnic hypoxic hypoxia is blunted in fetal sheep in utero at 93 days of gestation (term = 145-150 days), a time of rapid brain differentiation in this species. Cerebral O2 transport fell rather than being maintained, as it is in more mature fetuses. The reason for the blunted response was not clear. We hypothesized that the CBF response to hypercapnia also might be blunted. We studied 10 immature fetal sheep in utero at a mean gestational age of 92 days 24 h after catheters were placed into the superior sagittal sinus, axillary artery, and inferior vena cava. We raised the fetal arterial carbon dioxide tension (PaCO2) by changing the mother's inspired PCO2. CBF was measured before and during hypercapnia by the microsphere method. The overall increase in CBF in response to hypercapnia in immature fetuses was lower than in near-term fetuses. However, the difference was eliminated after correcting for differences in cerebral O2 consumption. This study failed to show any defect in the ability of cerebral vessels in immature fetal sheep to respond to carbon dioxide.

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Caffeine and Cerebral Blood Flow

The British Journal of Psychiatry ◽

10.1192/bjp.143.6.604 ◽

1983 ◽

Vol 143 (6) ◽

pp. 604-608 ◽

Cited By ~ 49

Author(s):

Roy J. Mathew ◽

Deborah L. Barr ◽

Maxine L. Weinman

Keyword(s):

Carbon Dioxide ◽

Blood Pressure ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Respiratory Rate ◽

Regional Cerebral Blood Flow ◽

Inhalation Technique ◽

Regional Cerebral Blood ◽

End Tidal Carbon Dioxide ◽

End Tidal

SummaryTwo groups of normal volunteers had regional cerebral blood flow (rCBF) measured, by the 133Xenon inhalation technique, before and 30 minutes after 250 mg or 500 mg caffeine given orally. rCBF was measured in a third group of subjects, twice, at a similar interval under identical laboratory conditions. Subjects who received caffeine showed significant decreases in rCBF while the others showed no rCBF change from the first to the second measurement. However, the two caffeine groups did not differ in degrees of rCBF reduction. There were no regional variations in the post-caffeine decrease in cerebral blood flow. The three groups did not show significant changes in end-tidal carbon dioxide, pulse rate, blood pressure, forehead skin temperature and respiratory rate.

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Influence of cerebral blood flow on breathing stability

Journal of Applied Physiology ◽

10.1152/japplphysiol.90914.2008 ◽

2009 ◽

Vol 106 (3) ◽

pp. 850-856 ◽

Cited By ~ 46

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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