EFFECTS OF FLOW HETEROGENEITY ON THE MEASUREMENT OF CAPILLARY EXCHANGE IN THE LUNG

The effects of flow heterogeneity on the measurement of transcapillary escape of small molecules for pet-fused in situ sheep lungs were evaluated. Lungs were studied at five flows (1.5-5.0 l/min) ranging from zone 1 to zone 3 conditions. At each flow, multiple indicator-dilution curves were collected using (14)C-labeled urea (U) or butanediol (B) as the diffusing tracer, and radiolabeled 15-mu m microspheres were injected. The lungs were removed, dried, sectioned, weighed, and counted for microsphere radioactivity. Flow heterogeneity, expressed as relative dispersion, decreased with increasing flow, from 0.838 +/- 0.179 (mean +/- SD, n = 8) to 0.447 +/- 0.119 (n = 6). We applied homogeneous flow models of capillary exchange to compute permeability-surface area product (PS) and a related parameter, D(1/2)S, for diffusing tracers. (D is effective diffusivity of capillary exchange.) PS and D(1/2)S increased to a maximum with increasing flow, but the ratio of D(1/2)S(U) to D(1/2)S(B) remained constant. A new model incorporating flow heterogeneity and recruitment (the variable recruitment model) was used. The variable recruitment model described the effects of flow on capillary recruitment, but incorporating heterogeneity into the computation did not alter D(1/2)S values from those computed assuming homogeneous flow.