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 (DLCO) and its components, capillary blood volume (Vc) and membrane diffusing capacity (Dm,CO). However the contribution of CBV to DLCO regulation remains poorly defined. We tested the hypothesis that graded increases and decreases in CBV would elicit differential changes in DLCO, primarily driven by Vc. Eighteen healthy young adults (6 women; age: 25 [3] years; V ̇ O 2 peak : 44.5 [8.5] mL/kg/min) completed supine graded lower body positive (LBPP) and negative pressure (LBNP). DLCO, Vc and Dm,CO were assessed using the combined DLCO,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 DLCO did not change (P = 0.589) due to a reciprocal increase in Vc (P = 0.009) and a decrease in Dm,CO (P < 0.001). In contrast LBNP elicited graded reductions in TFC (P < 0.001), DLCO (P < 0.001) and Vc (P < 0.001), with no change in Dm,CO (P = 0.610). Across LBPP and LBNP changes in TFC were associated with the corresponding changes in DLCO (P < 0.001) and Vc (P < 0.001), and Dm,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 Vc. KEY POINTS: Central blood volume (CBV) and pulmonary artery pressure are key determinants of pulmonary diffusing capacity for carbon monoxide (DLCO) and its components, capillary blood volume (Vc) and membrane diffusing capacity (Dm,CO); however the role of CBV in DLCO and its components has not yet been elucidated. During lower body positive pressure (increased CBV), DLCO did not change due to reciprocal increases in Vc and decreases in Dm,CO. During lower body negative pressure (central hypovolaemia), DLCO significantly declined, secondary to a decrease in Vc. DLCO and Vc exhibited non-linear relationships with thoracic fluid content (TFC, an index of CBV), whereas Dm,CO demonstrated a negative linear relationship with TFC. Our findings demonstrate that TFC-mediated Vc expansion alone is insufficient to augment DLCO, whereas central hypovolaemia reduces DLCO primarily via reduced capillary distention/recruitment.