The impact of biological sex and stroke volume constituents on heterogeneity in the Q–VO2 relationship and skeletal muscle saturation during cycling

Abstract Interindividual variability in the cardiac output () to the rate of oxygen consumption () slope (–) in healthy males is related to stroke volume (SV); however, the impact of differences in left ventricular (LV) structure and function as well as biological sex on this slope is unclear. The – slope, LV function, convective oxygen delivery and vastus lateralis skeletal muscle oxygen saturation were assessed in 42 untrained, healthy individuals (25 ± 5 years, 50% female) during submaximal semi‐upright cycling up to 120 W, followed by progressive exercise to exhaustion. There was considerable variability in the submaximal – slope (∆40–∆80 W; 1.8–11.8 L of blood/min per L of O 2 /min), though males and females did not differ (6.0 ± 2.2 vs. 4.9 ± 2.2 L of blood/min per L of O 2 /min; P = 0.140) despite males having a greater calculated blood volume ( P < 0.0001). The – slope was correlated positively to skeletal muscle desaturation (all r > 0.550, all P < 0.029) and negatively to arterial oxygen content ( r = −0.619, P = 0.005) in females only. Accounting for differences in filling time, SV heterogeneity was explained by preload, contractility, and biological sex ( F = 36.11; P < 0.0001, r 2 = 0.800). These findings suggest that the – slope in females is influenced by arterial oxygen content and impacts skeletal muscle oxygenation. This highlights potential biological sex differences in the underlying mechanisms matching oxygen delivery to oxygen demand, with females appearing more dependent upon skeletal muscle oxygen extraction to compensate for lower arterial oxygen content and blood volume. Further, SV heterogeneity in the – slope is explained by preload and contractility, but not afterload.