title: Indomethacin-induced impairment of regional cerebrovascular reactivity: implications for respiratory control.
abstract: Cerebrovascular reactivity impacts CO₂-[H(+)] washout at the central chemoreceptors and hence has marked influence on the control of ventilation. To date, the integration of cerebral blood flow (CBF) and ventilation has been investigated exclusively with measures of anterior CBF, which has a differential reactivity from the vertebrobasilar system and perfuses the brainstem. We hypothesized that: (1) posterior versus anterior CBF would have a stronger relationship to central chemoreflex magnitude during hypercapnia, and (2) that higher posterior reactivity would lead to a greater hypoxic ventilatory decline (HVD). End-tidal forcing was used to induce steady-state hyperoxic (300 mmHg P ET ,O₂) hypercapnia (+3, +6 and +9 mmHg P ET ,CO₂) and isocapnic hypoxia (45 mmHg P ET ,O₂) before and following pharmacological blunting (indomethacin; INDO; 1.45 ± 0.17 mg kg(-1)) of resting CBF and reactivity. In 22 young healthy volunteers, ventilation, intra-cranial arterial blood velocities and extra-cranial blood flows were measured during these challenges. INDO-induced blunting of cerebrovascular flow responsiveness (CVR) to CO₂ was unrelated to variability in ventilatory sensitivity during hyperoxic hypercapnia. Further results in a sub-group of volunteers (n = 9) revealed that elevations of P ET,CO₂ via end-tidal forcing reduce arterial-jugular venous gradients, attenuating the effect of CBF on chemoreflex responses. During isocapnic hypoxia, vertebral artery CVR was related to the magnitude of HVD (R(2) = 0.27; P < 0.04; n = 16), suggesting that CO₂-[H(+)] washout from central chemoreceptors modulates hypoxic ventilatory dynamics. No relationships were apparent with anterior CVR. As higher posterior, but not anterior, CVR was linked to HVD, our study highlights the importance of measuring flow in posterior vessels to investigate CBF and ventilatory integration.
authors: Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Kelowna, British Columbia, Canada.
authors: Ryan L
authors: RL
authors: Hoiland
authors: Philip N
authors: PN
authors: Ainslie
authors: Kevin W
authors: KW
authors: Wildfong
authors: Kurt J
authors: KJ
authors: Smith
authors: Anthony R
authors: AR
authors: Bain
authors: Chris K
authors: CK
authors: Willie
authors: Glen
authors: G
authors: Foster
authors: Brad
authors: B
authors: Monteleone
authors: Trevor A
authors: TA
authors: Day
mesh_terms: D000328:Adult; D002245:Carbon Dioxide / Q000097:blood; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000097:blood; D012018:Reflex; D012119:Respiration
chemical_list: D002317:Cardiovascular Agents; D002245:Carbon Dioxide; D010100:Oxygen; D007213:Indomethacin
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