Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans.
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.
Xie
Ailiang
A
Department of Medicine, University of Wisconsin, Madison, WI, USA.
Skatrud
James B
JB
Morgan
Barbara
B
Chenuel
Bruno
B
Khayat
Rami
R
Reichmuth
Kevin
K
Lin
Jenny
J
Dempsey
Jerome A
JA
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
D002245:Carbon Dioxide