Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans

Xie, Ailiang; Skatrud, James B.; Morgan, Barbara J.; Chenuel, Bruno; Khayat, Rami; Reichmuth, Kevin J.; Lin, Ji; Dempsey, Jerome A.

doi:10.1113/jphysiol.2006.110627

Cited by 139 publications

(196 citation statements)

References 65 publications

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“…Plasma levels of Indo were not taken, and it is possible that absorption times resulted in different plasma levels. However, we used a typical drug wash-in period, similar to a previous study (49). In addition, we did not use a placebo-controlled double-blinded study design; instead, each subject was used as his or her own control, and young adults (where only slight changes were noted) served as a control group for older adults.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Barnes

Casey

Hines

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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The augmentation index and central blood pressure increase with normal aging. Recently, cyclooxygenase (COX) inhibitors, commonly used for the treatment of pain, have been associated with transient increases in the risk of cardiovascular events. We examined the effects of the COX inhibitor indomethacin (Indo) on central arterial hemodynamics and wave reflection characteristics in young and old healthy adults. High-fidelity radial arterial pressure waveforms were measured noninvasively by applanation tonometry before (control) and after Indo treatment in young (25 Ϯ 5 yr, 7 men and 6 women) and old (64 Ϯ 6 yr, 5 men and 6 women) subjects. Aortic systolic (control: 115 Ϯ 3 mmHg vs. Indo: 125 Ϯ 5 mmHg, P Ͻ 0.05) and diastolic (control: 74 Ϯ 2 mmHg vs. Indo: 79 Ϯ 3 mmHg, P Ͻ 0.05) pressures were elevated after Indo treatment in older subjects, whereas only diastolic pressure was elevated in young subjects (control: 71 Ϯ 2 mmHg vs. Indo: 76 Ϯ 1 mmHg, P Ͻ 0.05). Mean arterial pressure increased in both young and old adults after Indo treatment (P Ͻ 0.05). The aortic augmentation index and augmented pressure were elevated after Indo treatment in older subjects (control: 30 Ϯ 5% vs. Indo 36 Ϯ 6% and control 12 Ϯ 1 mmHg vs. Indo: 18 Ϯ 2 mmHg, respectively, P Ͻ 0.05), whereas pulse pressure amplification decreased (change: 8 Ϯ 3%, P Ͻ 0.05). In addition, older subjects had a 61 Ϯ 11% increase in wasted left ventricular energy after Indo treatment (P Ͻ 0.05). In contrast, young subjects showed no significant changes in any of the variables of interest. Taken together, these results demonstrate that COX inhibition with Indo unfavorably increases central wave reflection and augments aortic pressure in old but not young subjects. Our results suggest that aging individuals have a limited ability to compensate for the acute hemodynamic changes caused by systemic COX inhibition.

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Section: Discussionmentioning

confidence: 99%

Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Barnes

Casey

Hines

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…The engineering concept of "loop gain" has been around since the 1980s in the respiratory control literature as a key cause of CSA [ 16 ]. More recently, alterations of cerebral blood fl ow have been proposed as a potential key factor in CSA [ 35 ] (see Fig. 19.1 ).…”

Section: Mechanismsmentioning

confidence: 98%

Central Sleep Apnea at High Altitude

Burgess

Ainslie

2016

Advances in Experimental Medicine and Biology

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The discovery of central sleep apnea (CSA) at high altitude is usually attributed to Angelo Mosso who published in 1898. It can occur in susceptible individuals at altitude above 2000 m, but at very high altitude, say above 5000 m, it will occur in most subjects. Severity is correlated with ventilatory responsiveness, particularly to hypoxia. Theoretically, it should spontaneously improve with time and acclimatization. Although the time course of resolution is not well described, it appears to persist for more than a month at 5000 m.It occurs due to the interaction of hypocapnia with stages 1 and 2 NREM sleep, in the presence of increased loop-gain. The hypocapnia is secondary to hypoxic ventilatory drive. With acclimatization, one might expect that the increase in PaO2 and cerebral blood flow (CBF) would mitigate the CSA. However, over time, both the hypoxic and hypercapnic ventilatory responses increase, causing an increase in loop gain which is a counteracting force.The severity of the CSA can be reduced by descent, supplemental oxygen therapy, oral or intravenous acetazolamide. Recent studies suggest that acute further increases in cerebral blood flow will substantially, but temporarily, reduce central sleep apnea, without altering acid based balance. Very recently, bi-level noninvasive ventilation has also been shown to help (mechanism unknown). Sleep quality can be improved independent of the presence of CSA by the use of benzodiazepine sedation.

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“…This is contrary to what we observed in patients, as the cerebrovascular response was blunted. In healthy individuals, XIE et al [27] showed that decreased cerebrovascular responsiveness to CO 2 stimulates the ventilatory response, suggesting that cerebrovascular sensitivity to CO 2 has great influence on the V9E responsiveness of the central chemoreceptors. It is possible that the mechanisms involved in the control of breathing and cerebrovascular regulation in COPD patients are independently altered (i.e.…”

Section: Physiological Response To Hypercapniamentioning

confidence: 99%

Decreased cerebrovascular response to CO₂in post-menopausal females with COPD: role of oxidative stress

Hartmann¹,

Pialoux²,

Leigh³

et al. 2012

Eur Respir J

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Chronic obstructive pulmonary disease (COPD) is associated with cerebrovascular abnormalities and an overproduction of reactive oxygen species. We hypothesised that COPD patients have oxidant-related cerebrovascular dysfunction. Our main objective was to evaluate cerebrovascular reactivity and its relationship with oxidative stress in females with COPD.We studied eight females with moderate COPD and 10 healthy female control subjects of similar age. Transcranial Doppler ultrasound assessed cerebral blood flow (CBF) velocity during hypercapnia. Plasma was assessed at rest for DNA oxidation, advanced oxidation protein products, lipid peroxidation, nitrotyrosine, antioxidant enzyme activity (glutathione peroxidase and catalase) and end-products of nitric oxide metabolism.Moderate COPD patients showed decreased cerebrovascular sensitivity to carbon dioxide (CO 2 ) (COPD 1.17¡0.54 versus control 2.15¡0.73 cm?s -1 ?mmHg -1 ; p,0.01). COPD patients had higher levels of DNA and lipid oxidation, advanced oxidation protein products and higher glutathione peroxidase activity (p,0.05). Controlling for measures of oxidative stress (DNA and lipid oxidation, and advanced oxidation protein product) eliminates statistically significant differences between the COPD and control groups in the CBF sensitivity to CO 2 . Females with moderate COPD were found to have cerebrovascular dysfunction. Our results suggest that increased levels of systemic oxidative stress may have implications in the cerebrovascular dysfunction observed during hypercapnia in COPD.

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Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans

Cited by 139 publications

References 65 publications

Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Central Sleep Apnea at High Altitude

Decreased cerebrovascular response to CO₂in post-menopausal females with COPD: role of oxidative stress

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Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans

Cited by 139 publications

References 65 publications

Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Cyclooxygenase inhibition augments central blood pressure and aortic wave reflection in aging humans

Central Sleep Apnea at High Altitude

Decreased cerebrovascular response to CO2in post-menopausal females with COPD: role of oxidative stress

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Product

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Decreased cerebrovascular response to CO₂in post-menopausal females with COPD: role of oxidative stress