title: Cerebrovascular responses to hypoxia and hypocapnia in high-altitude dwellers.
abstract: Cerebral blood flow is known to increase in response to hypoxia and to decrease with hypocapnia. It is not known, however, whether these responses are altered in high-altitude dwellers who are not only chronically hypoxic and hypocapnic, but also polycythaemic. Here we examined cerebral blood flow responses to hypoxia and hypocapnia, separately and together, in Andean high-altitude dwellers, including some with chronic mountain sickness (CMS), which is characterized by excessive polycythaemia. Studies were carried out at high altitude (Cerro de Pasco (CP), Peru; barometric pressure (P(B)) 450 mmHg) and repeated, following relief of the hypoxia, on the day following arrival at sea level (Lima, Peru; P(B) 755 mmHg). We compared these results with those from eight sea-level residents studied at sea level. In nine high-altitude normal subjects (HA) and nine CMS patients, we recorded middle cerebral artery mean blood flow velocity (MCAVm) using transcranial Doppler ultrasonography, and expressed responses as changes from baseline. MCAVm responses to hypoxia were determined by changing end-tidal partial pressure of oxygen (P(ET,O2)) from 100 to 50 mmHg, with end-tidal partial pressure of carbon dioxide clamped. MCAVm responses to hypocapnia were studied by voluntary hyperventilation with (P(ET,O2)) clamped at 100 and 50 mmHg. There were no significant differences between the cerebrovascular responses of the two groups to any of the interventions at either location. In both groups, the MCAVm responses to hypoxia were significantly greater at Lima than at CP (HA, 12.1 +/- 1.3 and 6.1 +/- 1.0%; CMS, 12.5 +/- 0.8 and 5.6 +/- 1.2%; P < 0.01 both groups). The responses at Lima were similar to those in the sea-level subjects (13.6 +/- 2.3%). The responses to normoxic hypocapnia in the altitude subjects were also similar at both locations and greater than those in sea-level residents. During hypoxia, both high-altitude groups showed responses to hypocapnia that were significantly smaller at Lima than at CP (HA, 2.17 +/- 0.23 and 3.29 +/- 0.34% mmHg(-1), P < 0.05; CMS, 1.87 +/- 0.16 and 3.23 +/- 0.24% mmHg(-1); P < 0.01). The similarity of the results from the two groups of altitude dwellers suggests that haematocrit is unlikely to greatly affect cerebrovascular reactivity to hypoxia and hypocapnia. The smaller vasodilatation to hypoxia and larger vasoconstriction to hypoxic hypocapnia at high altitude suggest that cerebrovascular responses may be impaired at the high altitude, i.e. a maladaptation. The changes in the responses within less than 24 h at sea level indicate that this impairment is rapidly reversible.
authors.affiliation: Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, UK. ugmljn@leeds.ac.uk
authors.forename: L J
authors.initials: LJ
authors.lastname: Norcliffe
authors.forename: M
authors.initials: M
authors.lastname: Rivera-Ch
authors.forename: V E
authors.initials: VE
authors.lastname: Claydon
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
authors.forename: F
authors.initials: F
authors.lastname: Leon-Velarde
authors.forename: O
authors.initials: O
authors.lastname: Appenzeller
authors.forename: R
authors.initials: R
authors.lastname: Hainsworth
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D000328:Adult; D000531:Altitude; D001783:Blood Flow Velocity; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D006801:Humans; D016857:Hypocapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male