Topographic basis of bimodal ventilation-perfusion distributions during bronchoconstriction in sheep

The distribution of ventilation-perfusion (V̇A/Q̇) ratios during bronchoconstriction measured with the multiple inert gases elimination technique is frequently bimodal. However, the topographic basis and the cause of that bimodality remain unknown. In this article, regional V̇A/Q̇ is quantified by three-dimensional positron emission tomography (PET) imaging of methacholine-induced bronchoconstriction in sheep. Regional V̇A/Q̇ ratios were calculated from the imaged kinetics of intravenously injected ¹³NN-saline bolus, assembled into global V̇A/Q̇ distributions, and used to estimate gas exchange. During bronchoconstriction, large regions with impaired tracer washout were observed adjacent to regions of normal ventilation. PET-derived V̇A/Q̇ distributions during bronchoconstriction were consistently bimodal, with areas of low V̇A/Q̇ receiving a large fraction of Q̇. The standard deviation of the V̇A/Q̇ distribution was 38% lower if small-scale (subresolution) heterogeneity (< 2.2 cm³) was ignored. Arterial blood gases predicted from PET data correlated well with measured values for Pa_O2 (r² = 0.91, p < 0.01) and Pa_CO2 (r² = 0.90, p < 0.01). We conclude that the bimodality of V̇A/Q̇ distributions in bronchoconstriction reflects the involvement of large contiguous regions of hypoventilation with substantial subresolution intraregional V̇A/Q̇ heterogeneity. Assessment of the subresolution V̇A/Q̇ heterogeneity is therefore essential to accurately quantify global gas exchange impairment during bronchoconstriction.