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

Abstract 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; : 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 . image 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.