Cerebral Autoregulation in Subjects Adapted and Not Adapted to High Altitude

Abstract

Background and Purpose-Impaired cerebral autoregulation (CA) from high-altitude hypoxia may cause high-altitude cerebral edema in newcomers to a higher altitude. Furthermore, it is assumed that high-altitude natives have preserved CA. However, cerebral autoregulation has not been studied at altitude. Methods-We studied CA in 10 subjects at sea level and in 9 Sherpas and 10 newcomers at an altitude of 4243 m by evaluating the effect of an increase of mean arterial blood pressure (MABP) with phenylephrine infusion on the blood flow velocity in the middle cerebral artery (Vmca), using transcranial Doppler. Theoretically, no change of Vmca in response to an increase in MABP would imply perfect autoregulation. Complete loss of autoregulation is present if Vmca changes proportionally with changes of MABP. Results-In the sea-level group, at a relative MABP increase of 23Ϯ4% during phenylephrine infusion, relative Vmca did not change essentially from baseline Vmca (2Ϯ7%, Pϭ0.36), which indicated intact autoregulation. In the Sherpa group, at a relative MABP increase of 29Ϯ7%, there was a uniform and significant increase of Vmca of 24Ϯ9% (PϽ0.0001) from baseline Vmca, which indicated loss of autoregulation. The newcomers showed large variations of Vmca in response to a relative MABP increase of 21Ϯ6%. Five subjects showed increases of Vmca of 22% to 35%, and 2 subjects showed decreases of Vmca of 21% and 23%. Conclusions-All Sherpas and the majority of the newcomers showed impaired CA. It indicates that an intact autoregulatory response to changes in blood pressure is probably not a hallmark of the normal human cerebral vasculature at altitude and that impaired CA does not play a major role in the occurrence of cerebral edema in newcomers to the altitude.

Cerebral Pressure–Flow Relationship in Lowlanders and Natives at High Altitude

“…The 22% lower MCAv in the HA natives compared with lowlanders in the present study is also different than this previous report, 15 where comparable MCAv was reported (Sherpa: 61 ± 11; lowlanders: 63±12 cm/second). Early studies have established that natives with chronic mountain sickness and related polycythemia have reductions in CBF compared with chronic mountain sickness-free natives and lowlanders (e.g.…”

“…Findings showed that HA Sherpa, and most lowlanders arriving to HA, had impaired cerebral pressure-flow responses at 4,243 m, as reflected in a more pressure-passive response to acute hypertension compared with a sea-level (SL) group in their cross-sectional study. 15 In their follow-up study, 16 it was reported that Sherpa who resided below 4,000 m had an intact pressure-flow response; however, in those residing above 4,000 m, the chronic exposure to hypoxia led to more pressure-passive responses, indicative of impaired cerebral autoregulation. 16 In addition, the impairment in steady-state (i.e.…”

“…14 In contrast to lowlanders at HA, we know of only two studies that have examined the cerebral pressure-flow relationship in natives to HA. 15,16 In their first study, Jansen et al 15 assessed the pressure-flow relationship during steady-state hypertensive changes in BP (i.e. 0 Hz), induced by pharmacological (i.e.…”

“…16 To date, however, there has not been a comprehensive examination of the dynamic pressure-flow relationship (using TFA) under spontaneous and driven conditions upon initial arrival and after acclimatization within the same subject population, or comparisons made with HA natives (e.g., Sherpa). As mentioned, Jansen et al 15 has applied supplemental oxygen (100%) to Sherpa, whereas another study has applied supplemental O 2 (100%) to lowlanders after initial arrival to HA. 9 Such hyperoxia, however, is known to have a direct vasoconstrictive influence on the cerebrovasculature, 17 and it is unknown how normalizing endtidal PO 2 (P ET O 2 ) in partially acclimatized lowlanders affects the cerebral pressure-flow response.…”

“…While this remodeling is occurring, there is a period of uncompensated hypoxia, which could influence the cerebral pressure-flow relationship. 18 Answering these questions would provide insight into whether observed changes in pressure-flow relationships are caused simply by the hypoxia 5,[9][10][11][12]15,16 or some additional influence of possible vascular remodeling 18 associated with HA exposure. We therefore attempted to address the following main questions: (1) Is the dynamic cerebral pressure-flow relationship impaired at HA (5,050 m) during spontaneous and nonpharmacological-induced elevations in BP variability?…”