Influence of sympathoexcitation at high altitude on cerebrovascular function and ventilatory control in humans

J Appl Physiol (1985). 2012 Oct;113(7):1058-67. doi: 10.1152/japplphysiol.00463.2012. Epub 2012 Jul 26.

Abstract

We sought to determine the influence of sympathoexcitation on dynamic cerebral autoregulation (CA), cerebrovascular reactivity, and ventilatory control in humans at high altitude (HA). At sea level (SL) and following 3-10 days at HA (5,050 m), we measured arterial blood gases, ventilation, arterial pressure, and middle cerebral blood velocity (MCAv) before and after combined α- and β-adrenergic blockade. Dynamic CA was quantified using transfer function analysis. Cerebrovascular reactivity was assessed using hypocapnia and hyperoxic hypercapnia. Ventilatory control was assessed from the hypercapnia and during isocapnic hypoxia. Arterial Pco(2) and ventilation and its control were unaltered following blockade at both SL and HA. At HA, mean arterial pressure (MAP) was elevated (P < 0.01 vs. SL), but MCAv remained unchanged. Blockade reduced MAP more at HA than at SL (26 vs. 15%, P = 0.048). At HA, gain and coherence in the very-low-frequency (VLF) range (0.02-0.07 Hz) increased, and phase lead was reduced (all P < 0.05 vs. SL). Following blockade at SL, coherence was unchanged, whereas VLF phase lead was reduced (-40 ± 23%; P < 0.01). In contrast, blockade at HA reduced low-frequency coherence (-26 ± 20%; P = 0.01 vs. baseline) and elevated VLF phase lead (by 177 ± 238%; P < 0.01 vs. baseline), fully restoring these parameters back to SL values. Irrespective of this elevation in VLF gain at HA (P < 0.01), blockade increased it comparably at SL and HA (∼43-68%; P < 0.01). Despite elevations in MCAv reactivity to hypercapnia at HA, blockade reduced (P < 0.05) it comparably at SL and HA, effects we attributed to the hypotension and/or abolition of the hypercapnic-induced increase in MAP. With the exception of dynamic CA, we provide evidence of a redundant role of sympathetic nerve activity as a direct mechanism underlying changes in cerebrovascular reactivity and ventilatory control following partial acclimatization to HA. These findings have implications for our understanding of CBF function in the context of pathologies associated with sympathoexcitation and hypoxemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Altitude*
  • Arterial Pressure / physiology
  • Blood Flow Velocity / physiology
  • Carbon Dioxide / metabolism
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • Cerebrovascular Circulation / physiology*
  • Female
  • Homeostasis / physiology*
  • Humans
  • Hypercapnia / metabolism
  • Hypercapnia / physiopathology
  • Hypocapnia / metabolism
  • Hypocapnia / physiopathology
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Male
  • Middle Cerebral Artery / metabolism
  • Middle Cerebral Artery / physiopathology
  • Pulmonary Ventilation / physiology*
  • Respiration
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiology*

Substances

  • Carbon Dioxide