Cerebral homeostasis and orthostatic responses in residents of the highest city in the world

Abstract Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. 15/13/17 healthy participants living at sea-level (LL), 3,800m (HL 3800m ) and 5,100m (HL 5100m ), respectively, and 31 additional highlanders with CMS living at 5,100m were recruited. Middle cerebral artery mean blood velocity (MCAv-transcranial Doppler ultrasound), cerebral oxygen delivery (CDO 2 ), mean blood pressure (MAP-finger plethysmography), heart rate variability (low/high frequency – LF/HF, respectively) and baroreflex sensitivity (BRS) were assessed during 3 phases of a tilt test; while sitting, during standing-up and while standing for 3min. Cerebral autoregulation index (ARI) was estimated (ΔMCAv %baseline )/ΔMAP %baseline ) in response to standing-up. Altitude and CMS were associated with hypoxemia and elevated hemoglobin concentration. While sitting, MAP increased, MCAv and LF power decreased with altitude but were not further affected by CMS and CDO 2 was preserved. BRS was comparable across all altitudes, but reduced with CMS. With standing-up, altitude and CMS were associated with a lesser reduction in MAP; ARI was unaffected by either altitude or CMS. Compared to sitting in lowlanders, standing was associated with preserved MCAv, CDO 2 and BRS across all altitudes. The LF/HF ratio increased in HL 5100m compared to LL and HL 3800m from sitting to standing. Likewise, in CMS while standing, MCAv was reduced but CDO 2 remained unaffected; however, CMS showed blunted LF power , HF power and LF/HF ratio responses to standing compared to sitting. Despite altitude- and CMS-associated hypoxemia, erythrocytosis and impaired blood pressure regulation (CMS only), cerebral homeostasis while sitting, standing-up and standing was overall preserved. The origin of CMS-related neurological symptoms remains to be established.