Cerebrovascular and ventilatory responses to acute normobaric hypoxia in girls and women

Abstract

Physiological responses to hypoxia in children are incompletely understood. We aimed to characterize cerebrovascular and ventilatory responses to normobaric hypoxia in girls and women. Ten healthy girls (9.9 ± 1.7 years; mean ± SD; Tanner stage 1 and 2) and their mothers (43.9 ± 3.5 years) participated. Internal carotid (ICA) and vertebral artery (VA) velocity, diameter and flow (Duplex ultrasound) was recorded pre‐ and post‐1 h of hypoxic exposure (FIO 2 = 0.126;~4000 m) in a normobaric chamber. Ventilation (V˙E) and respiratory drive (VT/TI) expressed as delta change from baseline (∆%), and end‐tidal carbon‐dioxide (PETCO 2) were collected at baseline (BL) and 5, 30 and 60 min of hypoxia (5/30/60 HYP). Heart rate (HR) and oxygen saturation (SpO2) were also collected at these time‐points. SpO2 declined similarly in girls (BL‐97%; 60HYP‐80%, P < 0.05) and women (BL‐97%; 60HYP‐83%, P < 0.05). Global cerebral blood flow (gCBF) increased in both girls (BL‐687; 60HYP‐912 mL·min−1, P < 0.05) and women (BL‐472; 60HYP‐651 mL·min−1, P < 0.01), though the ratio of ICA:VA (%) contribution to gCBF differed significantly (girls, 75:25%; women, 61:39%). The relative increase in V˙E peaked at 30HYP in both girls (27%, P < 0.05) and women (19%, P < 0.05), as did ∆%VT/TI (girls, 41%; women, 27%, P's < 0.05). Tidal volume (VT) increased in both girls and women at 5HYP, remaining elevated above baseline in girls at 30 and 60 HYP, but declined back toward baseline in women. Girls elicit similar increases in gCBF and ventilatory parameters in response to acute hypoxia as women, though the pattern and contributions mediating these responses appear developmentally divergent.

Bilateral regional extracranial blood flow regulation to hypoxia and unilateral duplex ultrasound measurement error

“…When assessed bilaterally, acute poikilocapnic hypoxia caused the same vasodilatation (ICAs 6.9 (3.7) vs. VAs 7.0 (3.8)%; P = 0.87) and comparable relative increases in blood flow and blood flow reactivity in the ICAs and VAs (Figure 2f,h). These regional blood flow responses to acute hypoxia are similar to those previously reported from studies employing the typical method of doubling unilateral measurements (Lewis et al., 2014; Morris et al., 2017; Willie et al., 2012). There are as many studies reporting that the increase in blood flow to hypoxia is mediated by vasodilatation in both ICAs and VAs to extreme (<80% ) poikilocapnic hypoxia (Lewis et al., 2014; Morris et al., 2017) or isocapnic hypoxia (Fernandes et al., 2018; Hoiland et al., 2017) as there are reporting no vasodilatation (Lafave et al., 2019; Ogoh et al., 2013; Willie et al., 2012; Willie, Smith, et al., 2014), with others suggesting regionally specific vasodilatation (Kellawan et al., 2017; Subudhi et al., 2014).…”

“…When assessed bilaterally, acute poikilocapnic hypoxia caused the same vasodilatation (ICAs 6.9 (3.7) vs. VAs 7.0 (3.8)%; P = 0.87) and comparable relative increases in blood flow and blood flow reactivity in the ICAs and VAs (Figure 2f,h). These regional blood flow responses to acute hypoxia are similar to those previously reported from studies employing the typical method of doubling unilateral measurements (Lewis et al, 2014;Morris et al, 2017;Willie et al, 2012). There are as many studies reporting that the increase in blood flow to hypoxia is mediated by vasodilatation in both ICAs and VAs to extreme (<80%…”

“…The secondary aim of this study was to investigate the measurement error in unilateral compared to bilateral calculations of extracranial blood flow. Although other stimuli might be used (e.g., carbon dioxide, exercise), we chose to examine the extracranial measurement error to acute poikilocapnic hypoxia as it has previously been shown to increase cerebral blood flow by approximately 30% for a 1–2 h period (Lewis et al., 2014; Morris et al., 2017). Based on the previously identified ratio‐scaling problem with FMD, we hypothesised that a negative relationship would exist between extracranial artery resting normoxic blood flow and the relative blood flow response to hypoxia.…”

Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy

“…3c-d). Unlike the lateral resolution, the axial resolution of the UFF-PAM system is determined by the detected ultrasound bandwidth [32], which is ~33 µm across the scanning range. For in vivo experiments, we usually reduce the volumetric frame rate to 0.3 Hz, with a PRR of 800 kHz, a 2D frame rate of 1 kHz, and a scanning step size of 15-19 μm.…”

The influence of sex and maturation on carotid and vertebral artery hemodynamics and associations with free-living (in)activity in 6–17-year-olds

“…A substantial increase in the ICA diameter with age has been reported in children, with larger ICA diameter in 10-19 year old youth compared to 4-9 year old children (33). In contrast, Morris et al (34) found girls (9.9  1.7 years) and women (43.9  3.5 years) had similar sized ICA diameter and vertebral artery (VA) diameter. Global CBF also increases with age up until about 8-10 years, then decreases through adolescence to adult values (35).…”