Challenging dynamic cerebral autoregulation across the physiological CO2 spectrum: Influence of biological sex and cardiac cycle

This study applied alterations in partial pressure of end-tidal carbon dioxide ($P_{\mathrm{ETC}{O}_2}$) to challenge dynamic cerebral autoregulation (dCA) responses across the cardiac cycle in both biological sexes. A total of 20 participants (10 females and 10 males; aged 19–34 years) performed 4-min bouts of repeated squat–stand manoeuvres (SSMs) at 0.05 and 0.10 Hz (randomized orders) with $P_{\mathrm{ETC}{O}_2}$ clamped at ∼40 mmHg. The protocol was repeated for hypercapnic (∼55 mmHg) and hypocapnic (∼20 mmHg) conditions. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) were insonated via transcranial Doppler ultrasound. Dynamic end-tidal forcing clamped $P_{\mathrm{ETC}{O}_2}$, and finger photoplethysmography quantified beat-to-beat changes in blood pressure. Linear regressions were performed for transfer function analysis metrics including power spectrum densities, coherence, phase, gain and normalized gain (nGain) with adjustment for sex. During hypercapnic conditions, phase metrics were reduced from eucapnic levels (all P < 0.009), while phase increased during the hypocapnic stage during both 0.05 and 0.10 Hz SSMs (all P < 0.037). Sex differences were present with females displaying greater gain and nGain systole metrics during 0.10 Hz SSMs (all P < 0.041). Across $P_{\mathrm{ETC}{O}_2}$ stages, females displayed reduced buffering against systolic aspects of the cardiac cycle and augmented gain. Sex-related variances in dCA could explain sex differences in the occurrence of clinical conditions such as orthostatic intolerance and stroke, though the effect of fluctuating sex hormones and contraceptive use on dCA metrics is not yet understood.