Differential effects of central blood volume loading and unloading on pulmonary diffusing capacity in humans

Central blood volume (CBV) is a key haemodynamic determinant of pulmonary diffusing capacity for carbon monoxide (DL_CO) and its components, capillary blood volume (V_c) and membrane diffusing capacity (D_m,CO). However the contribution of CBV to DL_CO regulation remains poorly defined. We tested the hypothesis that graded increases and decreases in CBV would elicit differential changes in DL_CO, primarily driven by V_c. Eighteen healthy young adults (6 women; age: 25 [3] years; ${\dot{V}}_{O_2\mathrm{peak}}$ : 44.5 [8.5] mL/kg/min) completed supine graded lower body positive (LBPP) and negative pressure (LBNP). DL_CO, V_c and D_m,CO were assessed using the combined DL_CO,NO approach at baseline and throughout LBPP and LBNP. Impedance cardiography-derived thoracic fluid content (TFC) was used as a proxy of CBV. LBPP induced a progressive increase in TFC (P < 0.001); however DL_CO did not change (P = 0.589) due to a reciprocal increase in V_c (P = 0.009) and a decrease in D_m,CO (P < 0.001). In contrast LBNP elicited graded reductions in TFC (P < 0.001), DL_CO (P < 0.001) and V_c (P < 0.001), with no change in D_m,CO (P = 0.610). Across LBPP and LBNP changes in TFC were associated with the corresponding changes in DL_CO (P < 0.001) and V_c (P < 0.001), and D_m,CO (P < 0.044). Collectively these findings demonstrate that, in the supine position, pulmonary gas transfer is dynamically influenced by relatively small perturbations in CBV, primarily via alterations in V_c. KEY POINTS: Central blood volume (CBV) and pulmonary artery pressure are key determinants of pulmonary diffusing capacity for carbon monoxide (DL_CO) and its components, capillary blood volume (V_c) and membrane diffusing capacity (D_m,CO); however the role of CBV in DL_CO and its components has not yet been elucidated. During lower body positive pressure (increased CBV), DL_CO did not change due to reciprocal increases in V_c and decreases in D_m,CO. During lower body negative pressure (central hypovolaemia), DL_CO significantly declined, secondary to a decrease in V_c. DL_CO and V_c exhibited non-linear relationships with thoracic fluid content (TFC, an index of CBV), whereas D_m,CO demonstrated a negative linear relationship with TFC. Our findings demonstrate that TFC-mediated V_c expansion alone is insufficient to augment DL_CO, whereas central hypovolaemia reduces DL_CO primarily via reduced capillary distention/recruitment.