Although several factors are known to influence nonuniformity of ventilatio
n, including lung mechanical properties (regional structure and compliance)
, external factors (chest wall, pleural pressure, heart), and ventilatory p
arameters (tidal and preinspiratory volume, flow rate), their relative cont
ributions are poorly understood. We studied five excised, unperfused, canin
e right-middle lobes under varied levels of tidal volume (VT), thus elimina
ting many factors affecting heterogeneity. Multiple-breath washouts of N-2
were analyzed for anatomic dead space volume (VDanat), nonuniformity of N-2
washout, and nonuniformity between joined acinar regions vs. that occurrin
g between larger joined regions. Approximately 80% of ventilation heterogen
eity was found among joined acinar regions at resting levels of VT, but inc
reasing VT reduced intra-acinar heterogeneity to about 25% of that found at
resting levels. Increasing VT had essentially no effect on VDanat and hete
rogeneity among larger joined regions. The results indicate that the magnit
ude of VT is a major influence on the dominant intra-acinar component of ve
ntilation heterogeneity and that VT effects on VDanat are likely due to per
fusion and/or influences normally external to the lobar structure.