Journal articles: 'Cardiovascular reactivity (CVR)'

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NASCHITZ, Jochanan E., Michael ROZENBAUM, Madeline FIELDS, Hillel ISSEROFF, Sean ENIS, Jay P. BABICH, Shannon PECK, et al. "Search for disease-specific cardiovascular reactivity patterns: developing the methodology." Clinical Science 108, no. 1 (December 15, 2004): 37–46. http://dx.doi.org/10.1042/cs20040092.

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Aberrations of CVR (cardiovascular reactivity), an expression of autonomic function, lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome has been observed. In the present study, we aimed to develop methodologies for assessing disease-specific CVR patterns. As a prototype, a population of 50 consecutive patients with FMF (familial Mediterranean fever) was studied and compared with control populations. A 10 min supine/30 min head-up tilt test with recording of the heart rate and blood pressure or the pulse transit time was performed. Five studies were conducted applying different methods. In each study, statistical analysis identified independent predictors of CVR in FMF. Based on regression coefficients of these predictors, a linear DS (discriminant score) was computed for every subject. Each study established an equation to assess CVR, calculate DS for FMF and determine the sensitivity and specificity of the DS cut-off. In each of the five studies, abnormal CVR was observed in FMF patients. The best accuracy (88% sensitivity and 90.1% specificity for FMF) was obtained by a method based on beat-to-beat heart rate and pulse transit time recordings. Data was processed by fractal and recurrence quantitative analysis with recordings in FMF patients compared with a mixed control population. Identification of disease-specific CVR patterns was possible with the methodologies described in the present study. In FMF, disease-specific CVR may be explained by the interplay between neuroendocrine loops specific to FMF with cardiovascular homoeostatic mechanisms. Recognition of disease-specific CVR patterns may advance the understanding of homoeostatic mechanisms and have implications in clinical practice.

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Knardahl, S., and E. D. Hendley. "Association between cardiovascular reactivity to stress and hypertension or behavior." American Journal of Physiology-Heart and Circulatory Physiology 259, no. 1 (July 1, 1990): H248—H257. http://dx.doi.org/10.1152/ajpheart.1990.259.1.h248.

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The spontaneously hypertensive rat (SHR) exhibits increased cardiovascular reactivity (CVR) to environmental stress and behavioral hyperactivity relative to the Wistar-Kyoto rat (WKY). This study sought to determine whether enhanced CVR to stress in the SHR is related to hypertension or to behavioral hyperactivity. By breeding SHR with WKY, followed by inbreeding, E. D. Hendley has developed two strains in which the hypertensive trait seems to be separated from the hyperactivity trait: the Wistar-Kyoto hypertensive (WK-HT) and the Wistar-Kyoto hyperactive (WK-HA) strains. Male SHR, WKY, WK-HT, and WK-HA rats were implanted with intravascular catheters and Doppler flow-velocity probes to record arterial pressure, heart rate (HR), and changes in regional vascular resistances. Five days after surgery, the rats were subjected to air-jet stress and pharmacological interventions. The hyperactive strains (SHR and WK-HA) exhibited enhanced pressor, renal, and mesenteric responses to stress, and higher HRs under all conditions, even after autonomic blockade. Both hypertension and hyperactivity were associated with reduced baroreceptor sensitivity. These data indicate that CVR to stress is related to behavioral traits.

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Ripp, T. M., and N. V. Rebrova. "The value of assessing cerebrovascular reactivity in hypertension and comorbid pathology." "Arterial’naya Gipertenziya" ("Arterial Hypertension") 27, no. 1 (April 7, 2021): 51–63. http://dx.doi.org/10.18705/1607-419x-2021-27-1-51-63.

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The review presents the rationale for the importance of studies on the reactivity of cerebral vessels, the classification of cerebrovascular reactivity (CVR) and the threshold values of quantitative indicators of the reserve phase and autoregulation of cerebral blood flow in healthy volunteers. Features of CVR in hypertension are described depending on the clinical course, daily blood pressure profile, the presence of comorbid pathology, the treatment approaches in treatment CVR disorders. We discuss the evidence-based data on the role of CVR assessment in diagnosing latent cerebral circulation insufficiency, prediction of cerebrovascular complications, monitoring the effectiveness and safety of drug and devise-based therapy of hypertension associated with abnormal CVR.

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Kessler, Thorsten, Bernhard Wolf, Niclas Eriksson, Daniel Kofink, Bakhtawar K. Mahmoodi, Himanshu Rai, Vinicius Tragante, et al. "Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention." Cardiovascular Research 115, no. 10 (February 14, 2019): 1512–18. http://dx.doi.org/10.1093/cvr/cvz015.

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AbstractAimA common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention.Methods and resultsThe association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91–209) vs. 134 (85–194) AU⋅min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203 AU⋅min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08–2.68; P = 0.02). Bleeding risk was not altered.ConclusionWe conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.

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Sobczyk, Olivia, Anne Battisti-Charbonney, Julien Poublanc, Adrian P. Crawley, Kevin Sam, Jorn Fierstra, Daniel M. Mandell, David J. Mikulis, James Duffin, and Joseph A. Fisher. "Assessing Cerebrovascular Reactivity Abnormality by Comparison to a Reference Atlas." Journal of Cerebral Blood Flow & Metabolism 35, no. 2 (November 12, 2014): 213–20. http://dx.doi.org/10.1038/jcbfm.2014.184.

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Attribution of vascular pathophysiology to reductions in cerebrovascular reactivity (CVR) is confounded by subjective assessment and the normal variation between anatomic regions. This study aimed to develop an objective scoring assessment of abnormality. CVR was measured as the ratio of the blood-oxygen-level-dependent magnetic resonance signal response divided by an increase in CO2, standardized to eliminate variability. A reference normal atlas was generated by coregistering the CVR maps from 46 healthy subjects into a standard space and calculating the mean and standard deviation (s.d.) of CVR for each voxel. Example CVR studies from 10 patients with cerebral vasculopathy were assessed for abnormality, by normalizing each patient's CVR to the same standard space as the atlas, and assigning a z-score to each voxel relative to the mean and s.d. of the corresponding atlas voxel. Z-scores were color coded and superimposed on their anatomic scans to form CVR z-maps. We found the CVR z-maps provided an objective evaluation of abnormality, enhancing our appreciation of the extent and distribution of pathophysiology compared with CVR maps alone. We concluded that CVR z-maps provide an objective, improved form of evaluation for comparisons of voxel-specific CVR between subjects, and across tests sites.

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Neumann, Serina A., Jessica R. P. Brown, Shari R. Waldstein, and Leslie I. Katzel. "A Walking Program’s Attenuation of Cardiovascular Reactivity in Older Adults with Silent Myocardial Ischemia." Journal of Aging and Physical Activity 14, no. 2 (April 2006): 119–32. http://dx.doi.org/10.1123/japa.14.2.119.

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Silent myocardial ischemia (SI) has been linked to increased risk of future coronary events. Enhanced systolic and diastolic blood pressure (SBP and DBP, respectively) and heart-rate (HR) reactions to stress (cardiovascular reactivity [CVR]) have been associated with greater severity of SI and are related prospectively to coronary-artery-disease endpoints. The authors examined the potential attenuating effects of 6 months of walking (aerobic exercise) versus control on CVR to three laboratory stressors in 25 older adults with exercise-induced SI. Maximal aerobic capacity was significantly improved by 12% for the exercise group and decreased by 8% for controls (p< .001). Groups had similar biomedical profiles pre- and postintervention. Walkers had significantly reduced DBP reactivity (pre, 12 ± 2; post, 4 ± 2 mm Hg) compared with controls (pre, 10 ± 2; post, 11 ± 2 mm Hg;p= .05), but no differences between groups were found for SBP or HR reactivity. These findings are the first to suggest that increased physical activity (via walking) can attenuate BP reactivity to emotional stressors in apparently healthy older adults with SI.

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Intzandt, Brittany, Dalia Sabra, Catherine Foster, Laurence Desjardins-Crépeau, Richard D. Hoge, Christopher J. Steele, Louis Bherer, and Claudine J. Gauthier. "Higher cardiovascular fitness level is associated with lower cerebrovascular reactivity and perfusion in healthy older adults." Journal of Cerebral Blood Flow & Metabolism 40, no. 7 (July 25, 2019): 1468–81. http://dx.doi.org/10.1177/0271678x19862873.

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Aging is accompanied by vascular and structural changes in the brain, which include decreased grey matter volume (GMV), cerebral blood flow (CBF), and cerebrovascular reactivity (CVR). Enhanced fitness in aging has been related to preservation of GMV and CBF, and in some cases CVR, although there are contradictory relationships reported between CVR and fitness. To gain a better understanding of the complex interplay between fitness and GMV, CBF and CVR, the present study assessed these factors concurrently. Data from 50 participants, aged 55 to 72, were used to derive GMV, CBF, CVR and VO2peak. Results revealed that lower CVR was associated with higher VO2peak throughout large areas of the cerebral cortex. Within these regions lower fitness was associated with higher CBF and a faster hemodynamic response to hypercapnia. Overall, our results indicate that the relationships between age, fitness, cerebral health and cerebral hemodynamics are complex, likely involving changes in chemosensitivity and autoregulation in addition to changes in arterial stiffness. Future studies should collect other physiological outcomes in parallel with quantitative imaging, such as measures of chemosensitivity and autoregulation, to further understand the intricate effects of fitness on the aging brain, and how this may bias quantitative measures of cerebral health.

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Schleiffer, R., F. Pernot, and A. Gairard. "Parathyroidectomy, cardiovascular reactivity and calcium distribution in aorta and heart of spontaneously hypertensive rats." Clinical Science 71, no. 5 (November 1, 1986): 505–11. http://dx.doi.org/10.1042/cs0710505.

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1. In order to elucidate the mechanisms by which parathyroidectomy (PTX), performed in young spontaneously hypertensive rats (SHR), delays the development and attenuates the level of hypertension, we studied, in vivo, cardiovascular reactivity (CVR, blood pressure response to bolus noradrenaline administration), aortic calcium distribution and cardiac calcium content in SHR with or without parathyroid glands. 2. PTX was performed in 6-week-old animals and experiments were done in pretreated anaesthetized animals 2 and 22 weeks after surgery. A significantly decreased CVR was observed 22 weeks after PTX in SHR-PTX as compared with controls. 3. These data are not specific for hypertensive animals since similar data are also obtained on nor-motensive Wistar rats treated in an identical fashion. In addition, after PTX in SHR and Wistar rats myocardial (auricle and ventricle) calcium content was more rapidly reduced (after 2 weeks) than aortic membrane-bound and cellular calcium fractions. 4. The present studies established that PTX decreases CVR and alters calcium content and distribution in the cardiovascular systems of rats from hypertensive and normotensive strains. Furthermore, the results confirm a requirement for the parathyroid glands in the pathogenesis of spontaneous hypertension in SHR and for the normal CVR.

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Reed, Joseph T., Tanya Pareek, Srinivas Sriramula, and Mallikarjuna R. Pabbidi. "Aging influences cerebrovascular myogenic reactivity and BK channel function in a sex-specific manner." Cardiovascular Research 116, no. 7 (November 18, 2019): 1372–85. http://dx.doi.org/10.1093/cvr/cvz314.

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Abstract Aims The myogenic reactivity of the middle cerebral arteries (MCA) protects the brain by altering the diameter in response to changes in lumen pressure. Large conductance potassium (BK) channels are known to regulate the myogenic reactivity, yet, it is not clear how aging alters the myogenic reactivity via the BK channel in males and females. Thus, we hypothesize that age-associated changes in BK channel subunits modulate the myogenic reactivity in a sex-specific manner. Methods and results We used vascular reactivity, patch-clamp, and biochemical methods to measure myogenic reactivity, BK channel function, and expression, respectively in cerebral vessels of adult and aged male and female Sprague Dawley rats. Our results suggest that aging and ovariectomy (OVX) exaggerated the myogenic reactivity of MCA in females but attenuated it in males. Aging induced outward eutrophic remodelling in females but inward hypertrophic remodelling in males. Aging decreased total, Kv, BK channel currents, and spontaneous transient outward currents (STOC) in vascular smooth muscle cells isolated from females, but not in males. Aging increased BKα subunit mRNA and protein both in males and females. However, aging decreased BKβ1 subunit protein and mRNA in females only. In males, BKβ1 mRNA is increased, but protein is decreased. Iberiotoxin-induced MCA constriction is lower in aged females but higher in aged males. Activation of BKα (10 µM NS1619) and BKβ1 (10 µM S-Equol) subunits failed to increase STOCs and were unable to decrease the myogenic reactivity of MCA in aged female but not in aged male rats. OVX decreased, but chronic supplementation of oestradiol restored BK channel expression and function. Conclusion Overall our results suggest that aging or OVX-associated downregulation of the BKβ1 expression and function in females results in exaggerated myogenic reactivity of MCA. However, age-associated increase in BK channel function in males attenuated myogenic reactivity of MCA.

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Flück, Daniela, Christoph Siebenmann, Stefanie Keiser, Adrian Cathomen, and Carsten Lundby. "Cerebrovascular Reactivity is Increased with Acclimatization to 3,454 M Altitude." Journal of Cerebral Blood Flow & Metabolism 35, no. 8 (March 25, 2015): 1323–30. http://dx.doi.org/10.1038/jcbfm.2015.51.

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Controversy exists regarding the effect of high-altitude exposure on cerebrovascular CO2 reactivity (CVR). Confounding factors in previous studies include the use of different experimental approaches, ascent profiles, duration and severity of exposure and plausibly environmental factors associated with altitude exposure. One aim of the present study was to determine CVR throughout acclimatization to high altitude when controlling for these. Middle cerebral artery mean velocity (MCAvmean) CVR was assessed during hyperventilation (hypocapnia) and CO2 administration (hypercapnia) with background normoxia (sea level (SL)) and hypoxia (3,454 m) in nine healthy volunteers (26 ± 4 years (mean ± s.d.)) at SL, and after 30 minutes (HA0), 3 (HA3) and 22 (HA22) days of high-altitude (3,454 m) exposure. At altitude, ventilation was increased whereas MCAvmean was not altered. Hypercapnic CVR was decreased at HA0 (1.16% ± 0.16%/mm Hg, mean ± s.e.m.), whereas both hyper- and hypocapnic CVR were increased at HA3 (3.13% ± 0.18% and 2.96% ± 0.10%/mm Hg) and HA22 (3.32% ± 0.12% and 3.24% ± 0.14%/mm Hg) compared with SL (1.98% ± 0.22% and 2.38% ± 0.10%/mm Hg; P < 0.01) regardless of background oxygenation. Cerebrovascular conductance (MCAvmean/mean arterial pressure) CVR was determined to account for blood pressure changes and revealed an attenuated response. Collectively our results show that hypocapnic and hypercapnic CVR are both elevated with acclimatization to high altitude.

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Blair, Gordon W., Fergus N. Doubal, Michael J. Thrippleton, Ian Marshall, and Joanna M. Wardlaw. "Magnetic resonance imaging for assessment of cerebrovascular reactivity in cerebral small vessel disease: A systematic review." Journal of Cerebral Blood Flow & Metabolism 36, no. 5 (February 16, 2016): 833–41. http://dx.doi.org/10.1177/0271678x16631756.

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Cerebral small vessel disease (SVD) pathophysiology is poorly understood. Cerebrovascular reactivity (CVR) impairment may play a role, but evidence to date is mainly indirect. Magnetic resonance imaging (MRI) allows investigation of CVR directly in the tissues affected by SVD. We systematically reviewed the use of MRI to measure CVR in subjects with SVD. Five studies (total n = 155 SVD subjects, 84 controls) provided relevant data. The studies included different types of patients. Each study used blood oxygen level dependent (BOLD) MRI to assess CVR but a different vasoactive stimulus and method of calculating CVR. CVR decreased with increasing white matter hyperintensities in two studies ( n = 17, 11%) and in the presence of microbleeds in another. Three studies ( n = 138, 89%) found no association of CVR with white matter hyperintensities. No studies provided tissue-specific CVR values. CVR decreased with age in three studies, and with female gender and increasing diastolic blood pressure in one study. Safety and tolerability data were limited. Larger studies using CVR appear to be feasible and are needed, preferably with more standardized methods, to determine if specific clinical or radiological features of SVD are more or less associated with impaired CVR.

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Zhao, Moss Y., Amanda Woodward, Audrey P. Fan, Kevin T. Chen, Yannan Yu, David Y. Chen, Michael E. Moseley, and Greg Zaharchuk. "Reproducibility of cerebrovascular reactivity measurements: A systematic review of neuroimaging techniques^*." Journal of Cerebral Blood Flow & Metabolism 42, no. 5 (November 22, 2021): 700–717. http://dx.doi.org/10.1177/0271678x211056702.

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Cerebrovascular reactivity (CVR), the capacity of the brain to increase cerebral blood flow (CBF) to meet changes in physiological demand, is an important biomarker to evaluate brain health. Typically, this brain “stress test” is performed by using a medical imaging modality to measure the CBF change between two states: at baseline and after vasodilation. However, since there are many imaging modalities and many ways to augment CBF, a wide range of CVR values have been reported. An understanding of CVR reproducibility is critical to determine the most reliable methods to measure CVR as a clinical biomarker. This review focuses on CVR reproducibility studies using neuroimaging techniques in 32 articles comprising 427 total subjects. The literature search was performed in PubMed, Embase, and Scopus. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified 5 factors of the experimental subjects (such as sex, blood characteristics, and smoking) and 9 factors of the measuring technique (such as the imaging modality, the type of the vasodilator, and the quantification method) that have strong effects on CVR reproducibility. Based on this review, we recommend several best practices to improve the reproducibility of CVR quantification in neuroimaging studies.

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Poublanc, Julien, Adrian P. Crawley, Olivia Sobczyk, Gaspard Montandon, Kevin Sam, Daniel M. Mandell, Paul Dufort, et al. "Measuring Cerebrovascular Reactivity: The Dynamic Response to a Step Hypercapnic Stimulus." Journal of Cerebral Blood Flow & Metabolism 35, no. 11 (July 1, 2015): 1746–56. http://dx.doi.org/10.1038/jcbfm.2015.114.

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We define cerebral vascular reactivity (CVR) as the ratio of the change in blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal (S) to an increase in blood partial pressure of CO2 (PCO2): % Δ S/Δ PCO2 mm Hg. Our aim was to further characterize CVR into dynamic and static components and then study 46 healthy subjects collated into a reference atlas and 20 patients with unilateral carotid artery stenosis. We applied an abrupt boxcar change in PCO2 and monitored S. We convolved the PCO2 with a set of first-order exponential functions whose time constant τ was increased in 2-second intervals between 2 and 100 seconds. The τ corresponding to the best fit between S and the convolved PCO2 was used to score the speed of response. Additionally, the slope of the regression between S and the convolved PCO2 represents the steady-state CVR (ssCVR). We found that both prolongations of τ and reductions in ssCVR (compared with the reference atlas) were associated with the reductions in CVR on the side of the lesion. τ and ssCVR are respectively the dynamic and static components of measured CVR.

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Wells, Jack A., Holly E. Holmes, James M. O'Callaghan, Niall Colgan, Ozama Ismail, Elizabeth MC Fisher, Bernard Siow, et al. "Increased Cerebral Vascular Reactivity in the Tau Expressing rTg4510 Mouse: Evidence against the Role of Tau Pathology to Impair Vascular Health in Alzheimer's Disease." Journal of Cerebral Blood Flow & Metabolism 35, no. 3 (March 2015): 359–62. http://dx.doi.org/10.1038/jcbfm.2014.224.

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Vascular abnormalities are a key feature of Alzheimer's disease (AD). Imaging of cerebral vascular reactivity (CVR) is a powerful tool to investigate vascular health in clinical populations although the cause of reduced CVR in AD patients is not fully understood. We investigated the specific role of tau pathology in CVR derangement in AD using the rTg4510 mouse model. We observed an increase in CVR in cortical regions with tau pathology. These data suggest that tau pathology alone does not produce the clinically observed decreases in CVR and implicates amyloid pathology as the dominant etiology of impaired CVR in AD patients.

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Tancredi, Felipe B., and Richard D. Hoge. "Comparison of Cerebral Vascular Reactivity Measures Obtained Using Breath-Holding and CO2 Inhalation." Journal of Cerebral Blood Flow & Metabolism 33, no. 7 (April 10, 2013): 1066–74. http://dx.doi.org/10.1038/jcbfm.2013.48.

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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.

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Anjali, Verma, Kumar Manoj, Adhana Ritu, Kumar Jay Ballabh, and Kaur Jaspreet. "Cardiovascular Reactivity (CVR) in Male Young Adults of Hypertensive Parents in North India." International Journal of Physiology 7, no. 4 (2019): 255. http://dx.doi.org/10.5958/2320-608x.2019.00181.1.

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Anjali, Verma, Kumar Manoj, Adhana Ritu, Kumar Jay Ballabh, and Kaur Jaspreet. "Cardiovascular reactivity (CVR) in male young adults of hypertensive parents in North India." MedPulse International Journal of Physiology 11, no. 1 (2019): 11–15. http://dx.doi.org/10.26611/1031114.

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Thomas, Binu P., Peiying Liu, Denise C. Park, Matthias JP van Osch, and Hanzhang Lu. "Cerebrovascular Reactivity in the Brain White Matter: Magnitude, Temporal Characteristics, and Age Effects." Journal of Cerebral Blood Flow & Metabolism 34, no. 2 (November 6, 2013): 242–47. http://dx.doi.org/10.1038/jcbfm.2013.194.

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White matter (WM) comprises about half of the brain and its dysfunction is implicated in many brain disorders. While structural properties in healthy and diseased WM have been extensively studied, relatively little is known about the physiology underlying these structural characteristics. Recent advances in magnetic resonance (MR) technologies provided new opportunities to better understand perfusion and microvasculature in the WM. Here, we aim to evaluate vasodilatory capacity of the WM vasculature, which is thought to be important in tissue ischemia and autoregulation. Fifteen younger and fifteen older subjects performed a CO2 inhalation task while blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging (MRI) images were continuously collected. The cerebrovascular reactivity (CVR) index showed that the value of CVR in the WM (0.03±0.002%/mm Hg) was positive, but was significantly lower than that in the gray matter (GM) (0.22±0.01%/mm Hg). More strikingly, the WM response showed a temporal delay of 19±3 seconds compared with GM, which was attributed to the longer time it takes for extravascular CO2 to change. With age, WM CVR response becomes greater and faster, which is opposite to the changes seen in the GM. These data suggest that characteristics of WM CVR are different from that of GM and caution should be used when interpreting pathologic WM CVR results.

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Smeeing, Diederik P. J., Jeroen Hendrikse, Esben T. Petersen, Manus J. Donahue, and Jill B. de Vis. "Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI Cerebrovascular Reactivity in Cerebrovascular Disease: A Systematic Review and Meta-Analysis." Cerebrovascular Diseases 42, no. 3-4 (2016): 288–307. http://dx.doi.org/10.1159/000446081.

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Background: The cerebrovascular reactivity (CVR) results of blood oxygen level-dependent (BOLD) and arterial spin labeling (ASL) MRI studies performed in patients with cerebrovascular disease (steno-occlusive vascular disease or stroke) were systematically reviewed. Summary: Thirty-one articles were included. Twenty-three (74.2%) studies used BOLD MRI to evaluate the CVR, 4 (12.9%) studies used ASL MRI and 4 (12.9%) studies used both BOLD and ASL MRI. Thirteen studies (3 significant) found a lower BOLD CVR, 2 studies found a similar CVR and 3 studies found a higher CVR in the ipsilateral compared to the contralateral hemisphere. Nine (5 significant) out of 10 studies found a lower BOLD CVR in the ipsilateral hemispheres of patients compared to controls. Six studies (2 significant) found a lower ASL CVR in the ipsilateral compared to the contralateral hemispheres. Three out of 5 studies found a significant lower ASL CVR in the ipsilateral hemispheres of patients compared to controls. Key Messages: This review brings support for a reduced BOLD and ASL CVR in the ipsilateral hemisphere of patients with cerebrovascular disease. We suggest that future studies will be performed in a uniform way so reference values can be established and could be used to guide treatment decisions in patients with cerebrovascular disease.

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Willie, Christopher K., David B. MacLeod, Kurt J. Smith, Nia C. Lewis, Glen E. Foster, Keita Ikeda, Ryan L. Hoiland, and Philip N. Ainslie. "The Contribution of Arterial Blood Gases in Cerebral Blood Flow Regulation and Fuel Utilization in Man at High Altitude." Journal of Cerebral Blood Flow & Metabolism 35, no. 5 (February 18, 2015): 873–81. http://dx.doi.org/10.1038/jcbfm.2015.4.

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The effects of partial acclimatization to high altitude (HA; 5,050 m) on cerebral metabolism and cerebrovascular function have not been characterized. We hypothesized (1) increased cerebrovascular reactivity (CVR) at HA; and (2) that CO2 would affect cerebral metabolism more than hypoxia. PaO2 and PaCO2 were manipulated at sea level (SL) to simulate HA exposure, and at HA, SL blood gases were simulated; CVR was assessed at both altitudes. Arterial–jugular venous differences were measured to calculate cerebral metabolic rates and cerebral blood flow (CBF). We observed that (1) partial acclimatization yields a steeper CO2-H+ relation in both arterial and jugular venous blood; yet (2) CVR did not change, despite (3) mean arterial pressure (MAP)-CO2 reactivity being doubled at HA, thus indicating effective cerebral autoregulation. (4) At SL hypoxia increased CBF, and restoration of oxygen at HA reduced CBF, but neither had any effect on cerebral metabolism. Acclimatization resets the cerebrovasculature to chronic hypocapnia.

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Hare, Hannah V., Michael Germuska, Michael E. Kelly, and Daniel P. Bulte. "Comparison of CO2 in Air Versus Carbogen for the Measurement of Cerebrovascular Reactivity with Magnetic Resonance Imaging." Journal of Cerebral Blood Flow & Metabolism 33, no. 11 (August 7, 2013): 1799–805. http://dx.doi.org/10.1038/jcbfm.2013.131.

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Measurement of cerebrovascular reactivity (CVR) can give valuable information about existing pathology and the risk of adverse events, such as stroke. A common method of obtaining regional CVR values is by measuring the blood flow response to carbon dioxide (CO2)-enriched air using arterial spin labeling (ASL) or blood oxygen level-dependent (BOLD) imaging. Recently, several studies have used carbogen gas (containing only CO2 and oxygen) as an alternative stimulus. A direct comparison was performed between CVR values acquired by ASL and BOLD imaging using stimuli of (1) 5% CO2 in air and (2) 5% CO2 in oxygen (carbogen-5). Although BOLD and ASL CVR values are shown to be correlated for CO2 in air (mean response 0.11 ± 0.03% BOLD, 4.46 ± 1.80% ASL, n = 16 hemispheres), this correlation disappears during a carbogen stimulus (0.36 ± 0.06% BOLD, 4.97 ± 1.30% ASL). It is concluded that BOLD imaging should generally not be used in conjunction with a carbogen stimulus when measuring CVR, and that care must be taken when interpreting CVR as measured by ASL, as values obtained from different stimuli (CO2 in air versus carbogen) are not directly comparable.

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Wu, Pei-Hsin, Ana E. Rodríguez-Soto, Zachary B. Rodgers, Erin K. Englund, Andrew Wiemken, Michael C. Langham, John A. Detre, Richard J. Schwab, Wensheng Guo, and Felix W. Wehrli. "MRI evaluation of cerebrovascular reactivity in obstructive sleep apnea." Journal of Cerebral Blood Flow & Metabolism 40, no. 6 (July 15, 2019): 1328–37. http://dx.doi.org/10.1177/0271678x19862182.

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Obstructive sleep apnea (OSA) is characterized by intermittent obstruction of the airways during sleep. Cerebrovascular reactivity (CVR) is an index of cerebral vessels' ability to respond to a vasoactive stimulus, such as increased CO2. We hypothesized that OSA alters CVR, expressed as a breath-hold index (BHI) defined as the rate of change in CBF or BOLD signal during a controlled breath-hold stimulus mimicking spontaneous apneas by being both hypercapnic and hypoxic. In 37 OSA and 23 matched non sleep apnea (NSA) subjects, we obtained high temporal resolution CBF and BOLD MRI data before, during, and between five consecutive BH stimuli of 24 s, each averaged to yield a single BHI value. Greater BHI was observed in OSA relative to NSA as derived from whole-brain CBF (78.6 ± 29.6 vs. 60.0 ± 20.0 mL/min2/100 g, P = 0.010) as well as from flow velocity in the superior sagittal sinus (0.48 ± 0.18 vs. 0.36 ± 0.10 cm/s2, P = 0.014). Similarly, BOLD-based BHI was greater in OSA in whole brain (0.19 ± 0.08 vs. 0.15 ± 0.03%/s, P = 0.009), gray matter (0.22 ± 0.09 vs. 0.17 ± 0.03%/s, P = 0.011), and white matter (0.14 ± 0.06 vs. 0.10 ± 0.02%/s, P = 0.010). The greater CVR is not currently understood but may represent a compensatory mechanism of the brain to maintain oxygen supply during intermittent apneas.

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Foudi, N., L. Louedec, T. Cachina, C. Brink, and X. Norel. "Selective cyclooxygenase-2 inhibition directly increases human vascular reactivity to norepinephrine during acute inflammation." Cardiovascular Research 81, no. 2 (December 1, 2008): 269–77. http://dx.doi.org/10.1093/cvr/cvn287.

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HELLER, B. A., D. J. PAULSON, S. J. KOPP, D. G. PEACE, and J. P. TOW. "Depressed in vivo myocardial reactivity to dobutamine in streptozotocin diabetic rats: influence of exercise training." Cardiovascular Research 22, no. 6 (June 1, 1988): 417–24. http://dx.doi.org/10.1093/cvr/22.6.417.

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Fisher, Joseph A. "The CO2 stimulus for cerebrovascular reactivity: Fixing inspired concentrations vs. targeting end-tidal partial pressures." Journal of Cerebral Blood Flow & Metabolism 36, no. 6 (March 21, 2016): 1004–11. http://dx.doi.org/10.1177/0271678x16639326.

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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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ARCHER, S., D. NELSON, R. GEBHARD, A. S. LEVINE, W. PRIGGE, and E. K. WEIR. "Effects of dietary fish oil on lung phospholipid fatty acid composition and intrinsic pulmonary vascular reactivity." Cardiovascular Research 21, no. 12 (December 1, 1987): 928–32. http://dx.doi.org/10.1093/cvr/21.12.928.

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Kirkeboen, K. A., G. Aksnes, and A. Ilebekk. "Coronary reactivity in the porcine heart after short lasting myocardial ischaemia: effects of duration of ischaemia and myocardial stunning." Cardiovascular Research 24, no. 12 (December 1, 1990): 998–1007. http://dx.doi.org/10.1093/cvr/24.12.998.

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De Vis, Jill B., Esben T. Petersen, Alex Bhogal, Nolan S. Hartkamp, Catharina JM Klijn, LJ Kappelle, and J. Hendrikse. "Calibrated MRI to Evaluate Cerebral Hemodynamics in Patients with an Internal Carotid Artery Occlusion." Journal of Cerebral Blood Flow & Metabolism 35, no. 6 (February 25, 2015): 1015–23. http://dx.doi.org/10.1038/jcbfm.2015.14.

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The purpose of this study was to assess whether calibrated magnetic resonance imaging (MRI) can identify regional variances in cerebral hemodynamics caused by vascular disease. For this, arterial spin labeling (ASL)/blood oxygen level-dependent (BOLD) MRI was performed in 11 patients (65±7 years) and 14 controls (66±4 years). Cerebral blood flow (CBF), ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were evaluated. The CBF was 34±5 and 36±11 mL/100 g per minute in the ipsilateral middle cerebral artery (MCA) territory of the patients and the controls. Arterial spin labeling CVR was 44±20 and 53±10% per 10 mm Hg ΔEtCO2 in patients and controls. The BOLD CVR was lower in the patients compared with the controls (1.3±0.8 versus 2.2±0.4% per 10 mm Hg ΔEtCO2, P < 0.01). The OEF was 41±8% and 38±6%, and the CMRO2 was 116±39 and 111±40 μmol/100 g per minute in the patients and the controls. The BOLD CVR was lower in the ipsilateral than in the contralateral MCA territory of the patients (1.2±0.6 versus 1.6±0.5% per 10 mmHg ΔEtCO2, P < 0.01). Analysis was hampered in three patients due to delayed arrival time. Thus, regional hemodynamic impairment was identified with calibrated MRI. Delayed arrival artifacts limited the interpretation of the images in some patients.

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Warnert, Esther AH, Ashley D. Harris, Kevin Murphy, Neeraj Saxena, Neeta Tailor, Nigel S. Jenkins, Judith E. Hall, and Richard G. Wise. "In vivo Assessment of Human Brainstem Cerebrovascular Function: A Multi-Inversion Time Pulsed Arterial Spin Labelling Study." Journal of Cerebral Blood Flow & Metabolism 34, no. 6 (March 5, 2014): 956–63. http://dx.doi.org/10.1038/jcbfm.2014.39.

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The brainstem (BS) is involved in critical physiologic processes, including control of cardiovascular and respiratory functions. This study implements a multi-inversion time pulsed arterial spin labelling (MTI PASL) imaging sequence that addresses the challenges of BS imaging and aims to measure normal and elevated BS perfusion in healthy volunteers. An initial experiment was performed to obtain the kinetic curve of the label in the BS and consequently to estimate the label arrival times and tissue perfusion in seven participants. A second experiment estimated the BS cerebral vascular reactivity (CVR) to hypercapnia in 10 participants. Images were acquired with a gradient-echo sequence with two spiral interleaves and short echo time (TE = 2.7 ms). Data were analyzed with a two-compartment model, including a tissue and arterial component. In both experiments, perfusion in the BS was significantly lower than in cortical gray matter (repeated measures analysis of variance (RM-ANOVA), P<0.05), which is as expected since the BS consists of gray and white matter, the latter typically showing lower perfusion. The BS CVR found here is comparable to previous reports obtained with positron emission tomography (PET) imaging. Multi-inversion time pulsed ASL in combination with a two-compartment signal model can be used to assess BS perfusion and CVR.

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Waheed, Nida, Suzette Elias-Smale, Waddah Malas, Angela H. Maas, Tara L. Sedlak, Jennifer Tremmel, and Puja K. Mehta. "Sex differences in non-obstructive coronary artery disease." Cardiovascular Research 116, no. 4 (January 20, 2020): 829–40. http://dx.doi.org/10.1093/cvr/cvaa001.

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Abstract Ischaemic heart disease is a leading cause of morbidity and mortality in both women and men. Compared with men, symptomatic women who are suspected of having myocardial ischaemia are more likely to have no obstructive coronary artery disease (CAD) on coronary angiography. Coronary vasomotor disorders and coronary microvascular dysfunction (CMD) have been increasingly recognized as important contributors to angina and adverse outcomes in patients with no obstructive CAD. CMD from functional and structural abnormalities in the microvasculature is associated with adverse cardiac events and mortality in both sexes. Women may be particularly susceptible to vasomotor disorders and CMD due to unique factors such as inflammation, mental stress, autonomic, and neuroendocrine dysfunction, which predispose to endothelial dysfunction and CMD. CMD can be detected with coronary reactivity testing and non-invasive imaging modalities; however, it remains underdiagnosed. This review focuses on sex differences in presentation, pathophysiologic risk factors, diagnostic testing, and prognosis of CMD.

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Jefferson, Angela L., Dandan Liu, Deepak K. Gupta, Kimberly R. Pechman, Jennifer M. Watchmaker, Elizabeth A. Gordon, Swati Rane, et al. "Lower cardiac index levels relate to lower cerebral blood flow in older adults." Neurology 89, no. 23 (November 8, 2017): 2327–34. http://dx.doi.org/10.1212/wnl.0000000000004707.

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Objective:To assess cross-sectionally whether lower cardiac index relates to lower resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) among older adults.Methods:Vanderbilt Memory & Aging Project participants free of stroke, dementia, and heart failure were studied (n = 314, age 73 ± 7 years, 59% male, 39% with mild cognitive impairment). Cardiac index (liters per minute per meter squared) was quantified from echocardiography. Resting CBF (milliliters per 100 grams per minute) and hypercapnia-induced CVR were quantified from pseudo-continuous arterial spin-labeling MRI. Linear regressions with ordinary least-square estimates related cardiac index to regional CBF, with adjustment for age, education, race/ethnicity, Framingham Stroke Risk Profile score (systolic blood pressure, antihypertensive medication use, diabetes mellitus, current cigarette smoking, left ventricular hypertrophy, prevalent cardiovascular disease [CVD], atrial fibrillation), APOE ε4 status, cognitive diagnosis, and regional tissue volume.Results:Lower cardiac index corresponded to lower resting CBF in the left (β = 2.4, p = 0.001) and right (β = 2.5, p = 0.001) temporal lobes. Results were similar when participants with prevalent CVD and atrial fibrillation were excluded (left temporal lobe β = 2.3, p = 0.003; right temporal lobe β = 2.5, p = 0.003). Cardiac index was unrelated to CBF in other regions assessed (p > 0.25) and CVR in all regions (p > 0.05). In secondary cardiac index × cognitive diagnosis interaction models, cardiac index and CBF associations were present only in cognitively normal participants and affected a majority of regions assessed with effects strongest in the left (p < 0.0001) and right (p < 0.0001) temporal lobes.Conclusions:Among older adults without stroke, dementia, or heart failure, systemic blood flow correlates with cerebral CBF in the temporal lobe, independently of prevalent CVD, but not CVR.

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Vidyasagar, Rishma, Arno Greyling, Richard Draijer, Douglas R. Corfield, and Laura M. Parkes. "The Effect of Black Tea and Caffeine on Regional Cerebral Blood Flow Measured with Arterial Spin Labeling." Journal of Cerebral Blood Flow & Metabolism 33, no. 6 (March 13, 2013): 963–68. http://dx.doi.org/10.1038/jcbfm.2013.40.

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Black tea consumption has been shown to improve peripheral vascular function. Its effect on brain vasculature is unknown, though tea contains small amounts of caffeine, a psychoactive substance known to influence cerebral blood flow (CBF). We investigated the effects on CBF due to the intake of tea components in 20 healthy men in a double-blinded, randomized, placebo-controlled study. On separate days, subjects received a single dose of 184 mg caffeine (equivalent to one strong espresso coffee), 2,820 mg black tea solids containing 184 mg caffeine (equivalent to 6 cups of tea), 2,820 mg decaffeinated black tea solids, or placebo. The CBF and cerebrovascular reactivity (CVR) to hypercapnia were measured with arterial spin labeled magnetic resonance imaging (MRI) before and 2 hours after administration. We found a significant global reduction with caffeine (20%) and tea (21%) in gray matter CBF, with no effect of decaffeinated tea, suggesting that only caffeine influences CBF acutely. Voxelwise analysis revealed the effect of caffeine to be regionally specific. None of the interventions had an effect on CVR. Additional research is required to conclude on the physiologic relevance of these findings and the chronic effects of caffeine and tea intake on CBF.

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Buratti, Laura, Giovanna Viticchi, Lorenzo Falsetti, Clotilde Balucani, Claudia Altamura, Cristina Petrelli, Leandro Provinciali, Fabrizio Vernieri, and Mauro Silvestrini. "Thresholds of impaired cerebral hemodynamics that predict short-term cognitive decline in asymptomatic carotid stenosis." Journal of Cerebral Blood Flow & Metabolism 36, no. 10 (July 22, 2016): 1804–12. http://dx.doi.org/10.1177/0271678x15613526.

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Subjects with asymptomatic carotid stenosis (ACS) may be at risk of cognitive impairment due to cerebral hypoperfusion. In this study, we aimed to detect a threshold of cerebral hemodynamics which is able to identify subjects at risk of cognitive deterioration. In subjects with ACS, cerebral vasomotor reactivity (CVR) was assessed with the breath-holding index (BHI) transcranial Doppler-based method. Cognitive deterioration was defined as a decrease in the MMSE score by ≥2 points after one year. In order to define the threshold of impaired BHI, a ROC curve analysis was performed adopting the binary difference of MMSE score as the outcome and continuous BHI as the testing variable. A total of 548 subjects completed the follow-up. Cognitive deterioration was observed in 119 patients (21.7%). The BHI value ipsilateral to the stenosis was the strongest predictor of cognitive deterioration among the variables tested. The best cut-point to discriminate between normal and abnormal BHI resulted ≤0.89. The post-test probability of cognitive deterioration for an abnormal BHI was 44%, while a normal BHI showed a post-test probability of 9% for the same outcome. The present investigation provides a threshold of reduced CVR that can be useful to identify subjects with ACS at risk of cognitive deterioration.

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Nakagawa, Ichiro, Shohei Yokoyama, Daisuke Wajima, Fumihiko Nishimura, Shuichi Yamada, Hiroshi Yokota, Yasushi Motoyama, et al. "Hyperventilation and breath-holding test with indocyanine green kinetics predicts cerebral hyperperfusion after carotid artery stenting." Journal of Cerebral Blood Flow & Metabolism 39, no. 5 (November 17, 2017): 901–12. http://dx.doi.org/10.1177/0271678x17743878.

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Cerebral hyperperfusion syndrome (CHS) is a serious complication following carotid artery stenting (CAS), but definitive early prediction of CHS has not been established. Here, we evaluated whether indocyanine green kinetics and near-infrared spectroscopy (ICG-NIRS) with hyperventilation (HV) and the breath-holding (BH) test can predict hyperperfusion phenomenon after CAS. The blood flow index (BFI) ratio during HV and BH was prospectively monitored using ICG-NIRS in 66 patients scheduled to undergo CAS. Preoperative cerebrovascular reactivity (CVR) and the postoperative asymmetry index (AI) were also assessed with single-photon emission computed tomography before and after CAS and the correlation with the BFI HV/rest ratio, BFI BH/rest ratio was evaluated. Twelve cases (18%) showed hyperperfusion phenomenon, and one (1.5%) showed CHS after CAS. A significant linear correlation was observed between the BFI HV/rest ratio, BFI BH/rest ratio, and preoperative CVR. A significant linear correlation was observed between the BFI HV/rest ratio and postoperative AI (r = 0.674, P < 0.0001). A BFI HV/rest ratio of 0.88 or more was the optimal cut-off point to predict hyperperfusion phenomenon according to receiver operating characteristic curve analyses. HV and BH test under ICG-NIRS is a useful tool for detection of hyperperfusion phenomenon in patients who underwent CAS.

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Furby, Hannah V., Esther AH Warnert, Christopher J. Marley, Damian M. Bailey, and Richard G. Wise. "Cardiorespiratory fitness is associated with increased middle cerebral arterial compliance and decreased cerebral blood flow in young healthy adults: A pulsed ASL MRI study." Journal of Cerebral Blood Flow & Metabolism 40, no. 9 (September 30, 2019): 1879–89. http://dx.doi.org/10.1177/0271678x19865449.

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Cardiorespiratory fitness is thought to have beneficial effects on systemic vascular health, in part, by decreasing arterial stiffness. However, in the absence of non-invasive methods, it remains unknown whether this effect extends to the cerebrovasculature. The present study uses a novel pulsed arterial spin labelling (pASL) technique to explore the relationship between cardiorespiratory fitness and arterial compliance of the middle cerebral arteries (MCAC). Other markers of cerebrovascular health, including resting cerebral blood flow (CBF) and cerebrovascular reactivity to CO2 (CVRCO2) were also investigated. Eleven healthy males aged 21 ± 2 years with varying levels of cardiorespiratory fitness (maximal oxygen uptake ([Formula: see text]O2MAX) 38–76 ml/min/kg) underwent MRI scanning at 3 Tesla. Higher [Formula: see text]O2MAX was associated with greater MCAC (R2 = 0.64, p < 0.01) and lower resting grey matter CBF (R2 = 0.75, p < 0.01). However, [Formula: see text]O2MAX was not predictive of global grey matter BOLD-based CVR (R2 = 0.47, p = 0.17) or CBF-based CVR (R2 = 0.19, p = 0.21). The current experiment builds upon the established benefits of exercise on arterial compliance in the systemic vasculature, by showing that increased cardiorespiratory fitness is associated with greater cerebral arterial compliance in early adulthood.

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Jain, Varsha, Michael C. Langham, Thomas F. Floyd, Gaurav Jain, Jeremy F. Magland, and Felix W. Wehrli. "Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia." Journal of Cerebral Blood Flow & Metabolism 31, no. 7 (April 20, 2011): 1504–12. http://dx.doi.org/10.1038/jcbfm.2011.34.

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The effect of hypercapnia on cerebral metabolic rate of oxygen consumption ( CMRO2) has been a subject of intensive investigation and debate. Most applications of hypercapnia are based on the assumption that a mild increase in partial pressure of carbon dioxide has negligible effect on cerebral metabolism. In this study, we sought to further investigate the vascular and metabolic effects of hypercapnia by simultaneously measuring global venous oxygen saturation ( Sv O2) and total cerebral blood flow ( tCBF), with a temporal resolution of 30 seconds using magnetic resonance susceptometry and phase-contrast techniques in 10 healthy awake adults. While significant increases in Sv O2 and tCBF were observed during hypercapnia ( P < 0.005), no change in CMRO2 was noted ( P > 0.05). Additionally, fractional changes in tCBF and end-tidal carbon dioxide ( R2 = 0.72, P < 0.005), as well as baseline Sv O2 and tCBF ( R2 = 0.72, P < 0.005), were found to be correlated. The data also suggested a correlation between cerebral vascular reactivity ( CVR) and baseline tCBF ( R2 = 0.44, P = 0.052). A CVR value of 6.1% ± 1.6%/mm Hg was determined using a linear-fit model. Additionally, an average undershoot of 6.7% ± 4% and 17.1% ± 7% was observed in Sv O2 and tCBF upon recovery from hypercapnia in six subjects.

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Yoneda, Hiroshi, Satoshi Shirao, Hiroyasu Koizumi, Fumiaki Oka, Hideyuki Ishihara, Kunitsugu Ichiro, Tetsuhiro Kitahara, Hidehiro Iida, and Michiyasu Suzuki. "Reproducibility of Cerebral Blood Flow Assessment using a Quantitative SPECT Reconstruction Program and Split-Dose 123I-Iodoamphetamine in Institutions with Different γ-Cameras and Collimators." Journal of Cerebral Blood Flow & Metabolism 32, no. 9 (May 23, 2012): 1757–64. http://dx.doi.org/10.1038/jcbfm.2012.67.

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Single photon emission computed tomography (SPECT) is used widely in clinical studies. However, the technique requires image reconstruction and the methods for correcting scattered radiation and absorption are not standardized among SPECT procedures. Therefore, quantitation of cerebral blood flow (CBF) may not be constant across SPECT models. The quantitative SPECT (QSPECT) software package has been developed for standardization of CBF. Using the QSPECT/dual-table autoradiographic (DTARG) method, CBF and cerebral vascular reactivity (CVR) at rest and after acetazolamide challenge can be evaluated using 123I-iodoamphetamine in a single SPECT session. In this study, we examined the reproducibility of quantitative regional CBF and CVR in QSPECT/DTARG using different SPECT models at two facilities. The subjects were nine patients with chronic cerebral ischemic disease who underwent QSPECT/DTARG at both facilities with use of different γ-cameras and collimators. There were significant correlations for CBF at rest and after acetazolamide challenge measured at the two facilities. The consistency of the CBFs of the patients measured at the two facilities were good in all cases. Our results show that CBF measured by QSPECT/DTARG in the same patients is reproducible in different SPECT models. This indicates that standardized evaluation of CBF can be performed in large multicenter studies.

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Watchmaker, Jennifer M., Meher R. Juttukonda, Larry T. Davis, Allison O. Scott, Carlos C. Faraco, Melissa C. Gindville, Lori C. Jordan, et al. "Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients." Journal of Cerebral Blood Flow & Metabolism 38, no. 9 (December 28, 2016): 1618–30. http://dx.doi.org/10.1177/0271678x16682509.

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Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38–0.45) compared to controls (interquartile range = 0.29–0.38), similar to participants with SCA (interquartile range = 0.37–0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.

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Waddle, Spencer L., Meher R. Juttukonda, Sarah K. Lants, Larry T. Davis, Rohan Chitale, Matthew R. Fusco, Lori C. Jordan, and Manus J. Donahue. "Classifying intracranial stenosis disease severity from functional MRI data using machine learning." Journal of Cerebral Blood Flow & Metabolism 40, no. 4 (May 8, 2019): 705–19. http://dx.doi.org/10.1177/0271678x19848098.

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Translation of many non-invasive hemodynamic MRI methods to cerebrovascular disease patients has been hampered by well-known artifacts associated with delayed blood arrival times and reduced microvascular compliance. Using machine learning and support vector machine (SVM) algorithms, we investigated whether arrival time-related artifacts in these methods could be exploited as novel contrast sources to discriminate angiographically confirmed stenotic flow territories. Intracranial steno-occlusive moyamoya patients ( n = 53; age = 45 ± 14.2 years; sex = 43 F) underwent (i) catheter angiography, (ii) anatomical MRI, (iii) cerebral blood flow (CBF)-weighted arterial spin labeling, and (iv) cerebrovascular reactivity (CVR)-weighted hypercapnic blood-oxygenation-level-dependent MRI. Mean, standard deviation (std), and 99th percentile of CBF, CVR, CVRDelay, and CVRMax were calculated in major anterior and posterior flow territories perfused by vessels with vs. without stenosis (≥70%) confirmed by catheter angiography. These and demographic variables were input into SVMs to evaluate discriminatory capacity for stenotic flow territories using k-fold cross-validation and receiver-operating-characteristic-area-under-the-curve to quantify variable combination relevance. Anterior circulation CBF-std, attributable to heterogeneous endovascular signal and prolonged arterial transit times, was the best performing single variable and CVRDelay-mean and CBF-std, both reflective of delayed vascular compliance, were a high-performing two-variable combination (specificity = 0.67; sensitivity = 0.75). Findings highlight the relevance of hemodynamic imaging and machine learning for identifying cerebrovascular impairment.

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Faraco, Carlos C., Megan K. Strother, Jeroen CW Siero, Daniel F. Arteaga, Allison O. Scott, Lori C. Jordan, and Manus J. Donahue. "The Cumulative Influence of Hyperoxia and Hypercapnia on Blood Oxygenation and R2*." Journal of Cerebral Blood Flow & Metabolism 35, no. 12 (July 15, 2015): 2032–42. http://dx.doi.org/10.1038/jcbfm.2015.168.

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Cerebrovascular reactivity (CVR)-weighted blood-oxygenation-level-dependent magnetic resonance imaging (BOLD-MRI) experiments are frequently used in conjunction with hyperoxia. Owing to complex interactions between hyperoxia and hypercapnia, quantitative effects of these gas mixtures on BOLD responses, blood and tissue R2∗, and blood oxygenation are incompletely understood. Here we performed BOLD imaging (3T; TE/TR = 35/2,000 ms; spatial resolution = 3×3×3.5 mm3) in healthy volunteers ( n = 12; age = 29±4.1 years) breathing (i) room air (RA), (ii) normocapnic-hyperoxia (95% O2/5% N2, HO), (iii) hypercapnic-normoxia (5% CO2/21% O2/74% N2, HC-NO), and (iv) hypercapnic-hyperoxia (5% CO2/95% O2, HC-HO). For HC-HO, experiments were performed with separate RA and HO baselines to control for changes in O2. T2-relaxation-under-spin-tagging MRI was used to calculate basal venous oxygenation. Signal changes were quantified and established hemodynamic models were applied to quantify vasoactive blood oxygenation, blood–water R∗2, and tissue-water R∗2. In the cortex, fractional BOLD changes (stimulus/baseline) were HO/RA = 0.011 ± 0.007; HC-NO/RA = 0.014±0.004; HC-HO/HO = 0.020±0.008; and HC-HO/RA = 0.035 ±0.010; for the measured basal venous oxygenation level of 0.632, this led to venous blood oxygenation levels of 0.660 (HO), 0.665 (HC-NO), and 0.712 (HC-HO). Interleaving a HC-HO stimulus with HO baseline provided a smaller but significantly elevated BOLD response compared with a HC-NO stimulus. Results provide an outline for how blood oxygenation differs for several gas stimuli and provides quantitative information on how hypercapnic BOLD CVR and R∗2 are altered during hyperoxia.

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Maxwell, Joseph D., Madeleine France, Lucy E. M. Finnigan, Howard H. Carter, Dick H. J. Thijssen, and Helen Jones. "Can exercise training enhance the repeated remote ischaemic preconditioning stimulus on peripheral and cerebrovascular function in high-risk individuals?" European Journal of Applied Physiology 121, no. 4 (January 28, 2021): 1167–78. http://dx.doi.org/10.1007/s00421-020-04580-6.

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Abstract Background Repeated exposure to remote ischaemic preconditioning (rIPC; short bouts of non-lethal ischaemia) enhances peripheral vascular function within 1 week; whereas, longer periods of rIPC (~ 1 year) may improve cerebral perfusion. Increasing the ‘dose’ of rIPC may lead to superior effects. Given the similarities between exercise and rIPC, we examined whether adding exercise to the rIPC stimulus leads to greater adaptation in systemic vascular function. Methods Nineteen individuals with increased risk for cardiovascular disease (CVD) were randomly allocated to either 8 weeks of rIPC (n = 9) or 8 weeks of rIPC + exercise (rIPC + Ex) (n = 10). rIPC was applied three times per week in both conditions, and exercise consisted of 50 min (70% heart rate max) of cycling 3 times per week. Peripheral endothelial function was assessed using flow-mediated dilation (FMD) before and after ischaemia–reperfusion (IR). Cerebrovascular function was assessed by dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVR), and cardio-respiratory fitness (VO2peak) using a maximal aerobic capacity test. Results FMD% increased by 1.6% (95% CI, 0.4, 2.8) following rIPC + Ex and by 0.3% (− 1.1, 1.5) in the only rIPC but this did not reach statistical significance (P = 0.65). Neither intervention evoked a change in dCA or in CVR (P > 0.05). VO2peak increased by 2.8 ml/kg/min (1.7, 3.9) following the rIPC + Ex and by 0.1 ml/kg/min (− 1.0, 1.4) following the rIPC only intervention (P = 0.69). Conclusion Combining exercise with rIPC across an 8-week intervention does not lead to superior effects in cerebrovascular and peripheral vascular function compared to a repeated rIPC intervention in individuals at risk of CVD.

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Deckers, Pieter T., Alex A. Bhogal, Mathijs BJ Dijsselhof, Carlos C. Faraco, Peiying Liu, Hanzhang Lu, Manus J. Donahue, and Jeroen CW Siero. "Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults." Journal of Cerebral Blood Flow & Metabolism 42, no. 5 (December 1, 2021): 861–75. http://dx.doi.org/10.1177/0271678x211064572.

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Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO2 or O2 does not affect CMRO2. We evaluated the null hypothesis that two common hypercapnic stimuli, ‘CO2 in air’ and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO2 were calculated for room-air, ‘CO2 in air’ and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for ‘CO2 in air’ and carbogen, respectively). CMRO2 decreased for ‘CO2 in air’ (−13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO2 during carbogen did not significantly change. Our findings indicate that ‘CO2 in air’ is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.

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Turner, J. Rick, Frank A. Treiber, Harry Davis, Joseph Rectanwald, Walter Pipkin, and William B. Strong. "Use of a virtual reality car-driving stressor in cardiovascular reactivity research." Behavior Research Methods, Instruments, & Computers 29, no. 3 (September 1997): 386–89. http://dx.doi.org/10.3758/bf03200591.

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Machado, Marcus Vinicius, Thais de Paola Chequer Barbosa, Thais Camasmine Chrispino, Fabricia Junqueira das Neves, Gabriel Dias Rodrigues, Pedro Paulo da Silva Soares, and Antonio Claudio Lucas da Nóbrega. "Cardiovascular and Autonomic Responses after a Single Bout of Resistance Exercise in Men with Untreated Stage 2 Hypertension." International Journal of Hypertension 2021 (March 29, 2021): 1–10. http://dx.doi.org/10.1155/2021/6687948.

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The aim of this paper is to assess the integrated responses of ambulatory blood pressure (BP), cardiac autonomic modulation, spontaneous baroreflex sensitivity (BRS), and vascular reactivity after a single bout of resistance exercise (RE) in men with stage 2 hypertension who have never been treated before. Ten hypertensive men were subjected to a RE session of three sets of 20 repetitions and an intensity of 40% of the 1-repetition maximum (RM) test in seven different exercises. For the control (CTR) session, the volunteers were positioned on the exercise machines but did not perform any exercise. Forearm blood flow was measured by venous occlusion plethysmography. We also analyzed the heart rate variability (HRV), ambulatory BP, blood pressure variability (BPV), and BRS. All measurements were performed at different timepoints: baseline, 20 min, 80 min, and 24 h after both RE and CTR sessions. There were no differences in ambulatory BP over the 24 h between the RE and CTR sessions. However, the area under the curve of diastolic BP decreased after the RE session. Heart rate (HR) and cardiac output increased for up to 80 and 20 min after RE, respectively. Similarly, forearm blood flow, conductance, and vascular reactivity increased 20 min after RE ( p < 0.05 ). In contrast, HRV and BRS decreased immediately after exercise and remained lower for 20 min after RE. We conclude that a single bout of RE induced an increase in vascular reactivity and reduced the pressure load by attenuating AUC of DBP in hypertensive individuals who had never been treated with antihypertensive medications.

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Kabbani, Samer S., Matthew W. Watkins, Taka Ashikaga, Edward F. Terrien, Peter A. Holoch, Burton E. Sobel, and David J. Schneider. "Platelet Reactivity Characterized Prospectively." Circulation 104, no. 2 (July 10, 2001): 181–86. http://dx.doi.org/10.1161/01.cir.104.2.181.

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Liu, Selina L., Saskia Schmuck, Jozef Z. Chorazcyzewski, Robert Gros, and Ross D. Feldman. "Aldosterone Regulates Vascular Reactivity." Circulation 108, no. 19 (November 11, 2003): 2400–2406. http://dx.doi.org/10.1161/01.cir.0000093188.53554.44.

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Suarez, Jose, and Osama O. Zaidat. "Cerebral vasomotor reactivity in brain dead patients." Stroke 32, suppl_1 (January 2001): 350. http://dx.doi.org/10.1161/str.32.suppl_1.350-a.

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P61 Background: Cerebral vasomotor reactivity (CVMR) is a measure of the changes in arteriolar resistance in response to changes in arterial C0 2 concentration. CMVR is easily performed at the bedside using transcranial Doppler ultrasound (TCD). CVMR has not been studied in brain death. Methods: Patients with a clinical diagnosis of brain death, confirmed by a neurointensivist, were studied. CVMR was determined at the time of the apnea test. An experienced sonographer used a Pioneer TC 2020 (Nicolette) with a 2 MHz probe to insonate a middle cerebral artery of these patients. Continuous middle cerebral artery blood flow velocity (MCAV), systolic blood pressure (SBP), heart rate (HR), body temperature, oxygen saturation, and end-tidal C0 2 was performed during the procedure.A confirmatory arterial blood gas was obtained at baseline, five and ten minutes into the apnea test, and three minutes after hyperventilation. CMVR was calculated as follows: (MCAV at hypercapnia/MCAV at baseline)x100 - (MCAV at hypocapnia/MCAV at baseline)x100.(Normal in adults: 86±16%) CMVR was then divided by the absolute change in C0 2 to yield the percentage change (%Δ) in MCAV per mmHg C0 2 (Normal in adults: 2–4%). Results: Ten patients were studied (8 men) with a mean age 47±16 years.Their underlying disease varied: 3 ischemic strokes, 3 ICH, 2 SAH and 2 anoxic encephalopathy. Values of parameters monitored during the apnea test for this population: SBP:140±25 mmHg, HR:90.6±31/min, temperature: 35.8±2, PC0 2 at baseline: 40.6±9, at end of test: 74.6±13, at hyperventilation: 33.3±5. CMVR was 43.5±20% and %Δ was 1.3±0.4. All these patients had MCAV patterns compatible with brain death. Conclusion: CMVR is severely reduced or exhausted in brain dead patients. This test should be considered when TCD is used as a confirmatory tool in clinically brain dead patients.

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da Cunha, Natalia Veronez, Phileno Pinge-Filho, Carolina Panis, Bruno Rodrigues Silva, Laena Pernomian, Marcella Daruge Grando, Rubens Cecchini, Lusiane Maria Bendhack, and Marli Cardoso Martins-Pinge. "Decreased endothelial nitric oxide, systemic oxidative stress, and increased sympathetic modulation contribute to hypertension in obese rats." American Journal of Physiology-Heart and Circulatory Physiology 306, no. 10 (May 15, 2014): H1472—H1480. http://dx.doi.org/10.1152/ajpheart.00520.2013.

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We investigated the involvement of nitric oxide (NO) and reactive oxygen species (ROS) on autonomic cardiovascular parameters, vascular reactivity, and endothelial cells isolated from aorta of monosodium glutamate (MSG) obese rats. Obesity was induced by administration of 4 mg/g body wt of MSG or equimolar saline [control (CTR)] to newborn rats. At the 60th day, the treatment was started with NG-nitro-l-arginine methyl ester (l-NAME, 20 mg/kg) or 0.9% saline. At the 90th day, after artery catheterization, mean arterial pressure (MAP) and heart rate were recorded. Plasma was collected to assess lipid peroxidation. Endothelial cells isolated from aorta were evaluated by flow cytometry and fluorescence intensity (FI) emitted by NO-sensitive dye [4,5-diaminofluoresceindiacetate (DAF-2DA)] and by ROS-sensitive dye [dihydroethidium (DHE)]. Vascular reactivity was made by concentration-response curves of acetylcholine. MSG showed hypertension compared with CTR. Treatment with l-NAME increased MAP only in CTR. The MSG induced an increase in the low-frequency (LF) band and a decrease in the high-frequency band of pulse interval. l-NAME treatment increased the LF band of systolic arterial pressure only in CTR without changes in MSG. Lipid peroxidation levels were higher in MSG and were attenuated after l-NAME. In endothelial cells, basal FI to DAF was higher in CTR than in MSG. In both groups, acetylcholine increased FI for DAF from basal. The FI baseline to DHE was higher in MSG than in CTR. Acetylcholine increased FI to DHE in the CTR group, but decreased in MSG animals. We suggest that reduced NO production and increased production of ROS may contribute to hypertension in obese MSG animals.

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Santos, M. Teresa, Juana Valles, Justo Aznar, Aaron J. Marcus, M. Johan Broekman, and Lenore B. Safier. "Prothrombotic Effects of Erythrocytes on Platelet Reactivity." Circulation 95, no. 1 (January 7, 1997): 63–68. http://dx.doi.org/10.1161/01.cir.95.1.63.

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Alhadid, Kenda, Amanda Robertson, Kirsten Walker, Andrea Kassner, Manohar Shroff, Gabrielle A. Deveber, William Logan, and Nomazulu Dlamini. "Abstract TP168: Quantitative Cerebrovascular Reactivity Atlas In Children." Stroke 53, Suppl_1 (February 2022). http://dx.doi.org/10.1161/str.53.suppl_1.tp168.

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Introduction: Cerebrovascular reactivity (CVR) can be measured by inducing carbon dioxide (CO 2 ) changes in the circulation and measuring subsequent changes in blood flow with functional MRI blood oxygen level dependent sequences (BOLD). In clinical practice, abnormalities in CVR imaging can serve as a biomarker of ischemic risk. To characterize pathological aberrations in CVR, it is essential to have quantitative reference data as to what constitutes normal CVR across brain regions at various stages of development. Methods: Prospective enrollment of healthy children ages 6 to 18. Target N of 40. Two datasets are being generated within the atlas using two different methods of administering the vasoactive stimulus (CO 2 ): a breath-hold CVR dataset (endogenous stimulus) and a RespirAct TM CVR dataset (exogenous). A test of normality is performed on CVR values for each voxel across subjects, with mean and standard deviation calculations. This will allow for generation of a Z-score for each CVR value per voxel in any clinical CVR study. Voxel-wide validation of breath-hold CVR values against the gold standard RespirAct TM CVR values will be performed using within subject t-test and between group comparisons. Subgroup analysis based on gender and age will also be performed. Results: Preliminary CVR data for 8 healthy right-handed children is presented (4 female, median age 13, range 9 -14 years). All participants tolerated CVR studies well and no side effects were reported. Group datasets acquired to date passed tests of normality with no significant differences in CVR values between the two methods found. Conclusions: This study will generate the first atlas of quantitative CVR-fMRI data in healthy children. Normative physiological data on CVR changes throughout childhood, and associations between CVR, blood pressure, age, and gender will be obtained. CVR imaging is performed clinically in patients with a risk of recurrent arterial ischemic stroke such as those with intracranial arteriopathies, sickle cell disease and other genetic and metabolic disorders. Our atlas can provide clinicians with objective measures regarding extent and distribution of CVR abnormalities, allow for stroke risk stratification, and aid in determining the optimal time for intervention.

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Journal articles on the topic 'Cardiovascular reactivity (CVR)'

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