title: Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans.
abstract: An important determinant of [H(+)] in the environment of the central chemoreceptors is cerebral blood flow. Accordingly we hypothesized that a reduction of brain perfusion or a reduced cerebrovascular reactivity to CO(2) would lead to hyperventilation and an increased ventilatory responsiveness to CO(2). We used oral indomethacin to reduce the cerebrovascular reactivity to CO(2) and tested the steady-state hypercapnic ventilatory response to CO(2) in nine normal awake human subjects under normoxia and hyperoxia (50% O(2)). Ninety minutes after indomethacin ingestion, cerebral blood flow velocity (CBFV) in the middle cerebral artery decreased to 77 +/- 5% of the initial value and the average slope of CBFV response to hypercapnia was reduced to 31% of control in normoxia (1.92 versus 0.59 cm(-1) s(-1) mmHg(-1), P < 0.05) and 37% of control in hyperoxia (1.58 versus 0.59 cm(-1) s(-1) mmHg(-1), P < 0.05). Concomitantly, indomethacin administration also caused 40-60% increases in the slope of the mean ventilatory response to CO(2) in both normoxia (1.27 +/- 0.31 versus 1.76 +/- 0.37 l min(-1) mmHg(-1), P < 0.05) and hyperoxia (1.08 +/- 0.22 versus 1.79 +/- 0.37 l min(-1) mmHg(-1), P < 0.05). These correlative findings are consistent with the conclusion that cerebrovascular responsiveness to CO(2) is an important determinant of eupnoeic ventilation and of hypercapnic ventilatory responsiveness in humans, primarily via its effects at the level of the central chemoreceptors.
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: Ailiang
authors.initials: A
authors.lastname: Xie
authors.forename: James B
authors.initials: JB
authors.lastname: Skatrud
authors.forename: Barbara
authors.initials: B
authors.lastname: Morgan
authors.forename: Bruno
authors.initials: B
authors.lastname: Chenuel
authors.forename: Rami
authors.initials: R
authors.lastname: Khayat
authors.forename: Kevin
authors.initials: K
authors.lastname: Reichmuth
authors.forename: Jenny
authors.initials: J
authors.lastname: Lin
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Dempsey
mesh_terms: D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D012016:Reference Values; D015656:Respiratory Mechanics; D013990:Tidal Volume
chemical_list: D002245:Carbon Dioxide