The effects of acute incremental hypocapnia on the magnitude of neurovascular coupling in healthy participants

Abstract

The high metabolic demand of cerebral tissue requires that local perfusion is tightly coupled with local metabolic rate (neurovascular coupling; NVC). During chronic altitude exposure, where individuals are exposed to the antagonistic cerebrovascular effects of hypoxia and hypocapnia, pH is maintained through renal compensation and NVC remains stable. However, the potential independent effect of acute hypocapnia and respiratory alkalosis on NVC remains to be determined. We hypothesized that acute steady-state hypocapnia via voluntary hyperventilation would attenuate the magnitude of NVC. We recruited 17 healthy participants and insonated the posterior cerebral artery (PCA) with transcranial Doppler ultrasound. NVC was elicited using a standardized strobe light stimulus (6 Hz; 5 × 30 s on/off) where absolute delta responses from baseline (BL) in peak, mean, and total area under the curve (tAUC) were quantified. From a BL end-tidal (P_ET )CO₂ level of 36.7 ± 3.2 Torr, participants were coached to hyperventilate to reach steady-state hypocapnic steps of Δ-5 Torr (31.6 ± 3.9) and Δ-10 Torr (26.0 ± 4.0; p < 0.001), which were maintained during the presentation of the visual stimuli. We observed a small but significant reduction in NVC peak (ΔPCAv) from BL during controlled hypocapnia at both Δ-5 (-1.58 cm/s) and Δ-10 (-1.37 cm/s), but no significant decrease in mean or tAUC NVC response was observed. These data demonstrate that acute respiratory alkalosis attenuates peak NVC magnitude at Δ-5 and Δ-10 Torr P_ET CO₂ , equally. Although peak NVC magnitude was mildly attenuated, our data illustrate that mean and tAUC NVC are remarkably stable during acute respiratory alkalosis, suggesting multiple mechanisms underlying NVC.

Keywords: hypocapnia; neurovascular coupling; respiratory alkalosis.

FIGURE 1

Protocol schematic and sample tracing. (a) Protocol schematic. There was a total of five 30‐s strobe light trials at resting P_ETCO₂ and both hypocapnic conditions. Breathing was coached during each intervention to reach targeted P_ETCO₂ (‐5 and ‐10 Torr). The order of hyperventilation and heavy hyperventilation trials was randomized between participants. (b) Raw tracing during one set of five light stimuli trials in a single participant. Visual stimulation was elicited with a 6 Hz strobe light, six inches from their eyes. Grey shaded regions denote periods of baseline and rest between VS trials with eyes closed

FIGURE 2

PCAv at baseline (BL) and during visual stimuli (strobe) in all three conditions (Δ0, Δ‐5, Δ‐10). (a–c) Absolute PCAv at BL compared with peak PCAv during visual stimulation across each condition. (d–f) Absolute mean PCAv at BL compared with mean PCAv during visual stimulation across each condition. (g–i) Absolute PCAv tAUC during BL compared with PCAv tAUC during visual stimulation. PCAv peak represents visually identified peak within each of the five strobe light stimulation. PCAv mean was collected from a total average of strobe light sections. Values are presented as mean ± SD. (*) indicates values significantly different from baseline (p < 0.001). These data confirm the presence of an NVC response under each condition, for each NVC analysis metric

FIGURE 3

A comparison of NVC response magnitude for each metric during normal P_ETCO₂ (Δ0) and both P_ETCO₂ conditions (Δ‐5, Δ‐10). (a) The magnitude (Δ) of the peak change in PCAv from baseline during visual stimulation compared across all three conditions. (b) The magnitude (Δ) of the mean change in PCAv from baseline during visual stimulation compared across all three (c). The magnitude (Δ) of the tAUC in PCAv from baseline during visual stimulation compared across all three conditions. (*) indicates values significantly different from baseline (p < 0.05)