Heterogeneity and matching of ventilation and perfusion within anatomical lung units in rats

Abstract

Prior studies exploring the spatial distributions of ventilation and perfusion have partitioned the lung into discrete regions not constrained by anatomical boundaries and may blur regional differences in perfusion and ventilation. To characterize the anatomical heterogeneity of regional ventilation and perfusion, we administered fluorescent microspheres to mark regional ventilation and perfusion in 5 Sprague-Dawley rats and then using highly automated computer algorithms, partitioned the lungs into regions defined by anatomical structures identified in the images. The anatomical regions ranged in size from the nearacinar to the lobar level. Ventilation and perfusion were well correlated at the smallest anatomical level. Perfusion and ventilation heterogeneity were relatively less in rats compared to data previously published in larger animals. The more uniform distributions may be due to a smaller gravitational gradient and/or the fewer number of generations in the distribution trees before reaching the level of gas exchange, making regional matching of ventilation and perfusion less extensive in small animals.

Comparison of CT-derived ventilation maps with deposition patterns of inhaled microspheres in rats

“…Such stars were not observed in our previous work (25, 28), and we are uncertain of their origin. We cannot accurately estimate their actual size, because the light they generated saturated the cryomicrotome camera’s CCD sensor making them appear larger due to blooming.…”

“…Similar FMS aerosols have been used in studies of ventilation and ventilation-perfusion heterogeneity (25, 28). Although the analysis of FMS data can only be performed on excised lungs and is therefore limited to non-clinical research, as a benchmark for non-invasive measures of ventilation heterogeneity it has the dual advantages that the particle deposition – and thereby ventilation – can be imaged in 3D and at extremely high resolution.…”

“…Although the analysis of FMS data can only be performed on excised lungs and is therefore limited to non-clinical research, as a benchmark for non-invasive measures of ventilation heterogeneity it has the dual advantages that the particle deposition – and thereby ventilation – can be imaged in 3D and at extremely high resolution. The latter enables an investigation of the scale at which registration-based estimates of regional ventilation remain accurate – an important datum for multiscale computational models of respiration and inhalation exposure, since previous studies have shown that ventilation heterogeneity persists down to the subacinar scale (28). Similarly, the scale at which these two measures correspond – ~3 mm in this study – would also indicate the scale at which registration-based measures of ventilation are predictive of aerosol deposition of particles at or below 1 μm diameter.…”

“…The Imaging Cryomicrotome (Barlow Scientific, Inc., Olympia, WA, USA) sections the frozen lung and photographs the tissue autofluorescence and FMS distribution at high resolution. The instrument has been previously described (27) but has been improved through several recent modifications (28). Briefly, it consists of a Redlake MegaPlus II ES 3200 digital camera (San Diego, CA) with a resolution of 2184 × 1472 pixels, a metal halide lamp (PE300BF Cermax, Excelitas Technologies, Fremont, CA), and filters limiting the excitation and emission wavelengths.…”

Ventilation/perfusion distributions revisited

“…The high spatial resolution, independent maps of V and Q have provided many insights into mechanisms of V A /Q heterogeneity over the last 15-20 years, most recently in examining V A /Q heterogeneity within and between anatomically defined lung units in rats [18].…”