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 (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) 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 (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean 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.

Can Alterations in Cerebrovascular CO2 Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?

“…As in previous studies [ 31 , 39 ], the magnitude response and time response of CVR ( τ ) determined by CO 2 inhalation, the traditional index of CVR, were attenuated during 50° HUT ( p < 0.001, Figure 1 and p = 0.001, Figure 2 , respectively). The physiological mechanism explaining the orthostatic stress-induced attenuation in CVR remains unknown, but it has been speculated that the attenuated CVR may reflect a progressively reduced cerebrovascular reserve to compensate for the increasingly unstable systemic circulation during orthostatic stress, which could ultimately lead to cerebral hypoperfusion and syncope [ 31 , 39 ]. In addition, orthostatic stress could influence the cerebrovasculature, including ventilation-perfusion matching that is distributed across the zones of the lung during these posture changes and affects PaCO 2 .…”

“…Given this background, the aim of the present study was to examine the validity of the method (TFA) under spontaneous respiration without CO 2 inhalation for assessing CVR. In our recent study [ 31 ], we observed that orthostatic stress (50° head-up tilt, HUT) attenuated CVR determined by traditional methods (i.e., magnitude response or time response, τ ). In the present study, the change in CVR during 50° HUT from supine was assessed using the TFA between middle cerebral artery blood velocity (MCA V) and predicted PaCO 2 during spontaneous respiration (at the operating point) to compare with CVR indices determined using the traditional methods with a CO 2 inhalation challenge.…”