Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers

Abstract

Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted "functional hyperemia." Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used -30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia.

Keywords: functional hyperemia; lower body negative pressure; neurovascular coupling.

Fig. 1.

A schematic diagram of the study designed employed in these determinations. CBFv, cerebral blood flow velocity; ET_CO2, end-tidal CO₂; AF, arm flexion; LBNP, lower body negative pressure; HR, heart rate; BP, blood pressure.

Fig. 2.

Baseline data obtained in the absence of AF and LBNP. Depicted are mean arterial pressure (MAP; top) and mean CBFv (mCBFv; bottom) power spectral densities [periodograms, oscillations in MAP (OAP) and oscillatory cerebral blood flow (OCBF), respectively] averaged over subjects and smoothed.

Fig. 3.

Paired power spectral densities of MAP (OAP) and CBFv (OCBF) during AF without oscillations in LBNP (OLBNP; A) and during OLBNP without AF [0.03 (B), 0.05 (C), and 0.10 Hz (D)] at each of the LBNP box oscillatory frequencies. The figure illustrates the spectral structure of individual signals at the different frequencies employed. Spectral estimates were obtained using an autoregressive method. AF had little effect on MAP spectrum with a small “bump” near 0.0083 Hz. However, AF marked increased OCBFv power centered at 0.0083 Hz. OLBNP produced large changes in both BP and CBFv at the LBNP box frequency.

Fig. 4.

The effects of OLBNP imposed at the frequencies shown, and AF on CBFv for a representative subject. The top panel (Baseline) shows CBFv in the absence of either AF or OLBNP. Note the diminution of CBFv oscillations with increasing OLBNP frequency.

Fig. 5.

The effects of OLBNP at 0.03, 0.05, and 0.10 Hz on functional hyperemia measured by the OCBF power near 0.0083 Hz due to AF. Data are averaged over all subjects. A: AF is compared with the absence of flexion (baseline, solid bars) and is shown as a log₁₀ of OCBF power during flexion − log₁₀ of OCBF power at baseline, or equivalently 10 × log₁₀(flexion/baseline) in decibels. Similarly, OLBNP with AF is compared with AF alone (open bars) = 10 × log₁₀(OLBNP + flexion/flexion), which is a negative quantity (OLBNP reduces flexion power). The net effect of first flexion and then OLBNP + flexion is equal to the sum of the logarithmic effects = log₁₀(flexion/baseline) + log₁₀(OLBNP + flexion/flexion) = log₁₀(OLBNP + flexion/baseline) and is close to zero. Therefore, oscillatory power is reduced nearly to baseline by 0.05 Hz (P < 0.01) and 0.10 Hz (P < 0.001) LBNP oscillations. B: the effect on OCBF power near 0.0083 Hz of adding AF (open bars) after first applying and maintaining OLBNP at 0.03, 0.05, and 0.10 Hz (shaded bars). There is no significant direct effect of OLBNP oscillations alone on OCBF power at 0.0083 Hz, and no significant effect of AF on OCBF power at 0.0083 Hz in the presence of OLBNP. Values are means ± SE. *Significant difference of the comparison.

Fig. 6.

The effects of OLBNP at 0.03, 0.05, and 0.10 Hz on OAP power at 0.0083 Hz due to AF. Data are averaged over all subjects and are logarithmic as in Fig. 5, with results expressed as decibels. A: AF alone compared with baseline (solid bars) has no effect on OAP power at OLBNP frequencies. AF is followed by OLBNP (open bars), while flexion continues. B: OLBNP is first applied (open bars) and maintained during subsequent AF. Logarithmic OAP power at 0.0083 Hz is increased at 0.03 (P < 0.025) and 0.05 Hz (P < 0.05). Increased power is reversed by the addition of AF to LBNP (shaded bars). Values are means ± SE. *Significant difference of the comparison.

Fig. 7.

The effect of AF (at 0.0083 Hz) on logarithmic OCBF velocity (OCBFv) power at 0.03, 0.05, and 0.10 Hz. A: AF alone compared with baseline (solid bars) has no effect on logarithmic power at OLBNP frequencies. AF is followed by OLBNP (open bars) while flexion continues. B: the effect of OLBNP compared with baseline (open bars) on OCBFv power when it is applied first. The addition of AF follows (shaded bars). Comparing OCBFv power in A and B suggests that it is reduced by AF at each frequency of OLBNP. Values are means ± SE. *Significant difference of the comparison.