scholarly journals Cyclooxygenase inhibition abolishes age-related differences in cerebral vasodilator responses to hypercapnia

2012 ◽  
Vol 112 (11) ◽  
pp. 1884-1890 ◽  
Author(s):  
Jill N. Barnes ◽  
John E. Schmidt ◽  
Wayne T. Nicholson ◽  
Michael J. Joyner

Blood flow and vasodilatory responses are altered by age in a number of vascular beds, including the cerebral circulation. To test the role of prostaglandins as regulators of cerebral vascular function, we examined cerebral vasodilator responses to CO2 (cerebrovascular reactivity) in young (26 ± 5 yr; 6 males/6 females) and older (65 ± 6 yr, 5 males/5 females) healthy humans before and after cyclooxygenase inhibition (using indomethacin). Middle cerebral artery velocity (MCAv) responses to stepped hypercapnia were measured before and 90 min after indomethacin. Changes in MCAv during the recovery from hypercapnia (vasoconstrictor responses) were also evaluated before and after indomethacin. Cerebrovascular reactivity was calculated using linear regression between MCAv and end-tidal CO2. Young adults demonstrated greater MCAv (55 ± 6 vs. 39 ± 5 cm/s: P < 0.05) and MCAv reactivity (1.67 ± 0.20 vs. 1.09 ± 0.19 cm·s−1·mmHg−1; P < 0.05) to hypercapnia compared with older adults ( P < 0.05). In both groups MCAv and MCAv reactivity decreased between control and indomethacin. Furthermore, the age-related differences in these cerebrovascular variables were abolished by indomethacin. During the recovery from hypercapnia, there were no age-related differences in MCAv reactivity; however, indomethacin significantly reduced the MCAv reactivity in both groups. Taken together, these results suggest that cerebral blood flow velocity and cerebrovascular reactivity are attenuated in aging humans, and may be due to a loss of prostaglandin-mediated vasodilation.

Pain Medicine ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 3012-3017
Author(s):  
Igor Petrušić ◽  
Ana Podgorac ◽  
Aleksandra Radojičić ◽  
Jasna Zidverc-Trajković

Abstract Background Previous studies suggest that increased cerebrovascular reactivity might be a feature of patients who have migraine with aura (MwA). The correlation between the clinical presentation of migraine with aura and transcranial Doppler parameters remains unclear. Objective The main aim of this study was to explore cerebral blood flow, vascular resistance, and cerebrovascular reactivity in women MwA. Also, the relationships between hemodynamic conditions and aura characteristics are examined. Design Cross-sectional study. Setting Headache Center, Neurology Clinic, Clinical Center of Serbia. Subjects Fifty-four women MwA and 49 healthy controls (HCs). Methods Transcranial Doppler sonography examination was used to determine blood flow mean velocity (MV) and pulsatility index (PI), as well as breath-holding index (BHI), in 15 arterial segments comprising the circle of Willis. Results A total of 54 women MwA and 49 HCs were studied. The PIs of all segments of the left and right middle cerebral arteries and the left and right anterior cerebral arteries were significantly higher in MwA with regards to HCs. Also, both the left and right BHIs were significantly higher in MwA than HCs. In addition, MVs of the right vertebral artery and the first segment of the basilar artery were significantly lower in MwA than HCs. Longer duration of migraine aura showed a weak negative correlation with the PI of the left posterior cerebral artery. Conclusions Our findings suggest increased vessel pulsatility, abnormal cerebrovascular reactivity, and decreased cerebral blood flow velocity in several arterial segments of the Willis circle in women MwA.


2019 ◽  
pp. 185-188
Author(s):  
Peter Novak

This case presents a patient with extreme fatigue and excessive sleepiness. The tilt test provoked decline in cerebral blood flow velocity (CBFv) associated with decline in end tidal CO2, indicative of hypocapnic cerebral hypoperfusion (HYCH). There was also mild small fiber neuropathy affecting predominantly autonomic fibers associated with mild autonomic dysfunction.


2020 ◽  
Vol 9 (12) ◽  
pp. 4088
Author(s):  
Shyan-Lung Lin ◽  
Shoou-Jeng Yeh ◽  
Ching-Kun Chen ◽  
Yu-Liang Hsu ◽  
Chih-En Kuo ◽  
...  

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.


2019 ◽  
Vol 30 (2) ◽  
pp. 525-533 ◽  
Author(s):  
J J Steventon ◽  
C Foster ◽  
H Furby ◽  
D Helme ◽  
R G Wise ◽  
...  

Abstract Long-term exercise interventions have been shown to be a potent trigger for both neurogenesis and vascular plasticity. However, little is known about the underlying temporal dynamics and specifically when exercise-induced vascular adaptations first occur, which is vital for therapeutic applications. In this study, we investigated whether a single session of moderate-intensity exercise was sufficient to induce changes in the cerebral vasculature. We employed arterial spin labeling magnetic resonance imaging to measure global and regional cerebral blood flow (CBF) before and after 20 min of cycling. The blood vessels’ ability to dilate, measured by cerebrovascular reactivity (CVR) to CO2 inhalation, was measured at baseline and 25-min postexercise. Our data showed that CBF was selectively increased by 10–12% in the hippocampus 15, 40, and 60 min after exercise cessation, whereas CVR to CO2 was unchanged in all regions. The absence of a corresponding change in hippocampal CVR suggests that the immediate and transient hippocampal adaptations observed after exercise are not driven by a mechanical vascular change and more likely represents an adaptive metabolic change, providing a framework for exploring the therapeutic potential of exercise-induced plasticity (neural, vascular, or both) in clinical and aged populations.


1993 ◽  
Vol 265 (6) ◽  
pp. H1899-H1908 ◽  
Author(s):  
G. C. Haidet

Aging significantly affects reflex cardiovascular (CV) responses to induced muscular contraction in anesthetized dogs. To further investigate whether age-related changes in alpha-adrenergic-mediated responses to muscular contraction contribute to these previously reported age-related changes in CV responses associated with advanced age, hemodynamic and regional blood flow (BF) responses at baseline and during hindlimb contraction (HLC) were evaluated both before and after alpha-blockade (alpha-AB) in older (8-14 yr old) and in younger (2-3 yr old) beagles during alpha-chloralose anesthesia. alpha-AB with phentolamine resulted in significant (P < 0.05) reductions in mean arterial pressure before and during HLC, regardless of age. However, age-related differences in the systemic vascular resistance, cardiac output, and stroke volume responses to HLC, observed before alpha-AB, were eliminated after phentolamine as the result of an age-related difference in each of these responses to alpha-AB. Baseline BF (microspheres) was unchanged after alpha-AB in seven of eight abdominal organs, regardless of age. However, reductions in BF during HLC were attenuated in seven of eight abdominal organs in the younger dogs after alpha-AB, but in none of these organs in the older dogs, indicative of diminished alpha-mediated vasoconstriction in these organs in the older dogs during HLC. Furthermore, the age-related difference in the combined BF reduction to all eight abdominal organs before alpha-AB was eliminated after alpha-AB. Finally, BF increases to two of four contracting muscles, as well as the combined increase in blood flow to all four contracting muscles, were attenuated after alpha-AB, regardless of age. These results demonstrate that alpha-blockade eliminates many of the age-related differences in CV responses to HLC observed before alpha-AB and suggest that alpha-adrenergic-mediated responses to HLC change with age in beagles.


1996 ◽  
Vol 271 (6) ◽  
pp. R1625-R1631 ◽  
Author(s):  
S. T. Davidge ◽  
C. A. Hubel ◽  
M. K. McLaughlin

We tested the hypothesis that an increase in endogenous lipid peroxidation over time is associated with an impairment of endothelium-dependent vascular function in resistance-sized mesenteric arteries that is due in part to alterations of arachidonate metabolism. Susceptibility to red blood cell hemolysis and sera levels of malondialdehyde were increased (P < 0.05) from 20 wk (n = 12) to 40 wk (n = 12) in female Sprague-Dawley rats. Arteries were studied in a myograph by examining the endothelial modification of phenylephrine vasoconstriction and the relaxation responses of the mesenteric arteries to methacholine. We observed the following. 1) An increase in sensitivity to alpha 1-adrenergic stimulation occurred between 20 and 40 wk of age. Cyclooxygenase inhibition decreased the sensitivity to phenylephrine only in the arteries from the 40-wk-old rats, indicating that a cyclooxygenase-dependent vasoconstrictor was modifying the phenylephrine response. 2) Nitric oxide synthase inhibition caused a greater increase in phenylephrine sensitivity in the arteries from the 20-wk-old rats than those from the 40-wk-old rats, indicating that nitric oxide modification of phenylephrine sensitivity decreased with age. 3) Endothelium-independent relaxations were not affected between 20 and 40 wk of age. 4) At 40 wk, the sensitivity to the methacholine-mediated relaxation response decreased without impairing the maximal relaxation response. This reduced sensitivity was removed with cyclooxygenase inhibition or thromboxane A2/prostaglandin H2 (PGH2) receptor blockade. 5) Aortas from the 40-wk-old rats had an increased expression of PGH synthase. Collectively, these observations indicate that, in the female rat, an increase in lipid peroxidation over time is associated with changes in endothelium-dependent vascular function that were due in part to a cyclooxygenase-dependent vasoconstrictor.


2013 ◽  
Vol 33 (6) ◽  
pp. 963-968 ◽  
Author(s):  
Rishma Vidyasagar ◽  
Arno Greyling ◽  
Richard Draijer ◽  
Douglas R Corfield ◽  
Laura M Parkes

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.


2019 ◽  
Vol 126 (6) ◽  
pp. 1525-1532 ◽  
Author(s):  
Jay R. Hydren ◽  
Ryan M. Broxterman ◽  
Joel D. Trinity ◽  
Jayson R. Gifford ◽  
Oh Sung Kwon ◽  
...  

Continuous passive leg movement (PLM) is a promising clinical assessment of the age-related decline in peripheral vascular function. To further refine PLM, this study evaluated the efficacy of a single PLM (sPLM), a simplified variant of the more established continuous movement approach, to delineate between healthy young and old men based on vascular function. Twelve young (26 ± 5 yr) and 12 old (70 ± 7 yr) subjects underwent sPLM (a single passive flexion and extension of the knee joint through 90°), with leg blood flow (LBF, common femoral artery with Doppler ultrasound), blood pressure (finger photoplethysmography), and leg vascular conductance (LVC) assessed. A receiver operator characteristic curve analysis was used to determine an age-specific cut score, and a factor analysis was performed to assess covariance. Baseline LBF and LVC were not different between groups ( P = 0.6). The high level of covariance and similar predictive value for all PLM-induced LBF and LVC responses indicates LBF, alone, can act as a surrogate variable in this paradigm. The peak sPLM-induced increase in LBF from baseline was attenuated in the old (Young: 717 ± 227, Old: 260 ± 97 ml/min, P < 0.001; cut score: 372 ml/min), as was the total LBF response (Young: 155 ± 67, Old: 26 ± 17 ml, P < 0.001; cut score: 58 ml). sPLM, a simplified version of PLM, exhibits the prerequisite qualities of a valid screening test for peripheral vascular dysfunction, as evidenced by an age-related attenuation in the peripheral hyperemic response and a clearly delineated age-specific cut score. NEW & NOTEWORTHY Single passive leg movement (sPLM) exhibits the prerequisite qualities of a valid screening test for peripheral vascular dysfunction. sPLM displayed an age-related reduction in the peripheral hemodynamic response for amplitude, duration, initial rate of change, and total change with clearly delineated age-specific cut scores. sPLM has a strong candidate variable that is a simple single numeric value, for which to appraise peripheral vascular function, the 45-s hyperemic response (leg blood flow area under the curve: 45 s).


2017 ◽  
Vol 38 (11) ◽  
pp. 2021-2032 ◽  
Author(s):  
Nolan S Hartkamp ◽  
Esben T Petersen ◽  
Michael A Chappell ◽  
Thomas W Okell ◽  
Maarten Uyttenboogaart ◽  
...  

Collateral blood flow plays a pivotal role in steno-occlusive internal carotid artery (ICA) disease to prevent irreversible ischaemic damage. Our aim was to investigate the effect of carotid artery disease upon cerebral perfusion and cerebrovascular reactivity and whether haemodynamic impairment is influenced at brain tissue level by the existence of primary and/or secondary collateral. Eighty-eight patients with steno-occlusive ICA disease and 29 healthy controls underwent MR examination. The presence of collaterals was determined with time-of-flight, two-dimensional phase contrast MRA and territorial arterial spin labeling (ASL) imaging. Cerebral blood flow and cerebrovascular reactivity were assessed with ASL before and after acetazolamide. Cerebral haemodynamics were normal in asymptomatic ICA stenosis patients, as opposed to patients with ICA occlusion, in whom the haemodynamics in both hemispheres were compromised. Haemodynamic impairment in the affected brain region was always present in symptomatic patients. The degree of collateral blood flow was inversely correlated with haemodynamic impairment. Recruitment of secondary collaterals only occurred in symptomatic ICA occlusion patients. In conclusion, both CBF and cerebrovascular reactivity were found to be reduced in symptomatic patients with steno-occlusive ICA disease. The presence of collateral flow is associated with further haemodynamic impairment. Recruitment of secondary collaterals is associated with severe haemodynamic impairment.


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