Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex

Abstract

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO₂) is an important mechanism that maintains CO₂ or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇_E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (V_mean) responses to acute hypercapnia (5% CO₂) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO₂-response delay (t ₀)] and time constant (τ). Onset response of V̇_E and PCA V_mean to changes in CO₂ was unchanged during 50° HUT compared with supine (τ: V̇_E, p = 0.707; PCA V_mean, p = 0.071 vs. supine) but the MCA V_mean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

Keywords: anterior cerebral blood flow; head-up tilt; hypercapnia; posterior cerebral blood flow; respiratory chemoreflex.

Figure 1

Single-exponential regression model, t₀; the response time latency from induction of carbon dioxide administration to change [CO₂-response delay], y₀, baseline value; and G, gain term, and τ; time constant of the fitted curve of exponential regression during CO₂ administration. Time 0 (t₀ = 0) refers to the start of CO₂ administration. The τ is the time (unit: second) from t₀ to reach 63.2% of the steady-state value.

Figure 2

Panel A: Continuous recording of predicted partial pressure of arterial CO₂ (PaCO₂) responses to CO₂ administration (5% CO₂) during supine (gray line) and 50° head-up tilt (HUT; black line) in one representative participant. The dash-dotted and smooth curve represent the exponential lines at supine and 50° HUT, respectively. Panel B: Group-averaged gain (G) of predicted PaCO₂ exponential fitting curves during supine and 50° HUT. Panel C: Grouped sum of CO₂-response delay (t₀) and time constant (τ) of predicted PaCO₂ exponential fitting curves during supine and 50° HUT. The predicted PaCO₂ was derived from P_ETCO₂ and V_t using the following equation (Jones et al., 1979); Predicted PaCO₂ = 5.5 + 0.9*P_ETCO₂–0.0021*V_t. Grouped data are shown as median and interquartile range with individual data points.

Figure 3

Dynamic cerebrovascular carbon dioxide (CO₂) reactivity and central respiratory chemoreflex were characterized using a single-exponential regression model. Panels A–C: Continuous recordings of middle and posterior cerebral artery mean blood velocities (MCA V_mean, A and PCA V_mean, B) and pulmonary ventilation (V̇_E, C) response to CO₂ administration (5% CO₂) during hypercapnia during supine (gray line) and 50° head-up tilt (HUT; black line) in one representative participant. The dash-dotted and smooth curve represent the exponential lines at supine and 50° HUT, respectively. Panels D–F: Grouped gain (G, D), CO₂-response delay (t₀, E), and time constant (τ, F) of MCA V_mean, PCA V_mean, and V̇_E exponential fitting curves during supine and 50° HUT. Grouped data are shown as median and interquartile range with individual data points.