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Impact of hypocapnia and cerebral perfusion on orthostatic tolerance.

Publication ,  Journal Article
Lewis, NCS; Bain, AR; MacLeod, DB; Wildfong, KW; Smith, KJ; Willie, CK; Sanders, ML; Numan, T; Morrison, SA; Foster, GE; Stewart, JM; Ainslie, PN
Published in: J Physiol
December 1, 2014

We examined two novel hypotheses: (1) that orthostatic tolerance (OT) would be prolonged when hyperventilatory-induced hypocapnia (and hence cerebral hypoperfusion) was prevented; and (2) that pharmacological reductions in cerebral blood flow (CBF) at baseline would lower the 'CBF reserve', and ultimately reduce OT. In study 1 (n = 24; aged 25 ± 4 years) participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope; end-tidal carbon dioxide (P ET , CO 2) was clamped at baseline levels (isocapnic trial) or uncontrolled. In study 2 (n = 10; aged 25 ± 4 years), CBF was pharmacologically reduced by administration of indomethacin (INDO; 1.2 mg kg(-1)) or unaltered (placebo) followed by LBNP to pre-syncope. Beat-by-beat measurements of middle cerebral artery blood flow velocity (MCAv; transcranial Doppler), heart rate (ECG), blood pressure (BP; Finometer) and end-tidal gases were obtained continuously. In a subset of subjects' arterial-to-jugular venous differences were obtained to examine the independent impact of hypocapnia or cerebral hypoperfusion (following INDO) on cerebral oxygen delivery and extraction. In study 1, during the isocapnic trial, P ET , CO 2 was successfully clamped at baseline levels at pre-syncope (38.3 ± 2.7 vs. 38.5 ± 2.5 mmHg respectively; P = 0.50). In the uncontrolled trial, P ET , CO 2 at pre-syncope was reduced by 10.9 ± 3.9 mmHg (P ≤ 0.001). Compared to the isocapnic trial, the decline in mean MCAv was 15 ± 4 cm s(-1) (35%; P ≤ 0.001) greater in the uncontrolled trial, yet the time to pre-syncope was comparable between trials (544 ± 130 vs. 572 ± 180 s; P = 0.30). In study 2, compared to placebo, INDO reduced resting MCAv by 19 ± 4 cm s(-1) (31%; P ≤ 0.001), but time to pre-syncope remained similar between trials (placebo: 1123 ± 138 s vs. INDO: 1175 ± 212 s; P = 0.53). The brain extracted more oxygen in face of hypocapnia (34% to 53%) or cerebral hypoperfusion (34% to 57%) to compensate for reductions in delivery. In summary, cerebral hypoperfusion either at rest or induced by hypocapnia at pre-syncope does not impact OT, probably due to a compensatory increase in oxygen extraction.

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Published In

J Physiol

DOI

EISSN

1469-7793

Publication Date

December 1, 2014

Volume

592

Issue

23

Start / End Page

5203 / 5219

Location

England

Related Subject Headings

  • Young Adult
  • Syncope, Vasovagal
  • Sex Characteristics
  • Posture
  • Physiology
  • Oxygen
  • Male
  • Lower Body Negative Pressure
  • Indomethacin
  • Hypocapnia
 

Citation

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Lewis, N. C. S., Bain, A. R., MacLeod, D. B., Wildfong, K. W., Smith, K. J., Willie, C. K., … Ainslie, P. N. (2014). Impact of hypocapnia and cerebral perfusion on orthostatic tolerance. J Physiol, 592(23), 5203–5219. https://doi.org/10.1113/jphysiol.2014.280586
Lewis, Nia C. S., Anthony R. Bain, David B. MacLeod, Kevin W. Wildfong, Kurt J. Smith, Christopher K. Willie, Marit L. Sanders, et al. “Impact of hypocapnia and cerebral perfusion on orthostatic tolerance.J Physiol 592, no. 23 (December 1, 2014): 5203–19. https://doi.org/10.1113/jphysiol.2014.280586.
Lewis NCS, Bain AR, MacLeod DB, Wildfong KW, Smith KJ, Willie CK, et al. Impact of hypocapnia and cerebral perfusion on orthostatic tolerance. J Physiol. 2014 Dec 1;592(23):5203–19.
Lewis, Nia C. S., et al. “Impact of hypocapnia and cerebral perfusion on orthostatic tolerance.J Physiol, vol. 592, no. 23, Dec. 2014, pp. 5203–19. Pubmed, doi:10.1113/jphysiol.2014.280586.
Lewis NCS, Bain AR, MacLeod DB, Wildfong KW, Smith KJ, Willie CK, Sanders ML, Numan T, Morrison SA, Foster GE, Stewart JM, Ainslie PN. Impact of hypocapnia and cerebral perfusion on orthostatic tolerance. J Physiol. 2014 Dec 1;592(23):5203–5219.
Journal cover image

Published In

J Physiol

DOI

EISSN

1469-7793

Publication Date

December 1, 2014

Volume

592

Issue

23

Start / End Page

5203 / 5219

Location

England

Related Subject Headings

  • Young Adult
  • Syncope, Vasovagal
  • Sex Characteristics
  • Posture
  • Physiology
  • Oxygen
  • Male
  • Lower Body Negative Pressure
  • Indomethacin
  • Hypocapnia