Structural and Functional Determinants of Oxygen Transport in Exercise: The Role of Total Hemoglobin Mass

Abstract

Cardiac hemodynamics during exercise depend on both structural and functional adaptations of the oxygen transport system. This narrative review summarizes the knowledge on total hemoglobin mass (tHbmass) as a structural determinant of convective oxygen transport, and cardiac output and hemodynamic responses as key functional determinants, with attention to sex-related differences and clinical translation. We describe carbon monoxide rebreathing as the preferred method for quantifying tHbmass, outline typical values in untrained and endurance-trained men and women, and discuss the contributions of genetics, training, altitude exposure, and blood manipulation to inter-individual variation. The association between tHbmass and maximal oxygen uptake, its sport-specific distribution, and emerging clinical applications in the differential diagnosis of anemia and risk stratification are highlighted. We then review the regulation of cardiac output and arteriovenous oxygen difference during dynamic exercise, compare invasive and noninvasive techniques for their assessment, and summarize consistent sex differences in stroke volume, cardiac output, blood volume, and oxygen-carrying capacity. Across both domains, major gaps remain, particularly in the paucity of data in women and elite athletes studied at or near their physiological limits. Integrative assessments combining tHbmass, blood volume, and exercise hemodynamics may improve the understanding of both normal performance and cardiovascular pathology.