Disparate Effects Of Biological Sex On Oxygen Delivery And Skeletal Muscle Oxygenation

The cardiac output (Q̇) to oxygen consumption (V̇O2) relationship (Q̇-V̇O2) is the amount of Q̇ required to facilitate an increase in V̇O2 by 1 L/min. Previous work in males found that variability in the Q̇-V̇O2 relationship was independent of arterial oxygen content (CaO2) and did not impact active skeletal muscle oxygen saturation (SmO2). However, the influence of CaO2 on Q̇-V̇O2 variability and the relationship between Q̇-V̇O2 and SmO2 in females remains unknown. PURPOSE: To explore the effect of biological sex on the relationship between CaO2 and SmO2 to Q̇-V̇O2 heterogeneity respectively in males and females. METHODS: Thirty-five healthy, recreationally active individuals (25 ± 5 yr, 57% male) completed semi-upright cycling on a tilt-recline stress echocardiography table ergometer. 5-minutes of semi-upright rest and cycling at 40 W and 80 W was completed alongside assessments of Q̇ (2D echocardiography), V̇O2 (breath-by-breath indirect calorimetry) and SmO2 (near-infrared spectroscopy, right vastus lateralis) during steady state. ΔQ̇-V̇O2 was assessed as the slope between 40-80 W (Δ from rest). A resting venous blood sample was collected to compute CaO2. Blood volume was estimated using the Nadler equation. RESULTS: The ΔQ̇-V̇O2 relationship for the entire cohort ranged between 1.8 to 11.8 L of blood/min per L of O2/min, though males and females did not differ (6.0 ± 2.2 vs. 5.2 ± 2.3 L of blood/min per L of O2/min; p = 0.317) despite males having greater calculated blood volume (5.1 L vs 3.7 L; p < 0.001). ΔQ̇-V̇O2 had a strong positive correlation with ΔSmO2 desaturation at 40 W (r = 0.550, p = 0.042) and 80 W (r = 0.583, p = 0.029) in females, but not males (both r < -0.310, both p > 0.183). ΔQ̇-V̇O2 also had a strong negative correlation with CaO2 (r = -0.619, p = 0.005) in females, but not males (r = -0.087, p = 0.715). CONCLUSION: ΔQ̇-V̇O2 is related to CaO2 and SmO2 in females only suggesting a biological sex difference in mechanisms of matching oxygen delivery to oxygen demand. Females appear dependent upon greater skeletal muscle oxygen extraction to compensate for lower CaO2 and blood volume. Future investigations should assess active leg blood flow to further elucidate how the matching of oxygen delivery to oxygen demand during exercise is influenced by local vascular control between males and females. NSERC Discovery Grant and NSERC CGS M