Background: The slope of phase III (SIII) of the volumetric capnogram is proposed as a noninvasive marker of ventilation/perfusion ratio ( ) mismatch. However, direct comparisons of SIII with measurements of lung ventilation and perfusion distribution are lacking, particularly in acute bronchoconstriction. This study was developed to assess the relationship between SIII and distribution of lung ventilation ( ) and perfused blood volume (V B ), a surrogate of perfusion, using synchrotron radiation K-edge subtraction imaging in a rabbit model of methacholine-induced acute bronchoconstriction.

Methods: Five anesthetized, mechanically ventilated rabbits underwent imaging of and V B using K-edge subtraction imaging computed tomography before and after methacholine-induced bronchoconstriction and subsequent salbutamol administration. Mean , V B , /V B , and their heterogeneity were quantified. SIII was measured from exhaled volumetric capnograms. Multiple linear regression was used to evaluate the relative contributions of and V B to SIII.

Results: Methacholine-induced ventilation defects decreased both (mean difference [d] = 0.22, 95% CI, 0.12 to 0.51; P < 0.001) and V B (d = 1.9 ⋅ 10 -3 ; 95% CI, 1.0 × 10 -3 to 2.8 × 10 -3 ; P < 0.001) and increased their heterogeneity (d = 0.42; 95% CI, 0.17 to 0.67; P < 0.001; and d = 0.12; 95% CI, 0.05 to 0.19; P < 0.001, respectively). Salbutamol thereafter improved respiratory elastance (d = 726.2; CI, 130.9 to 1,321; P = 0.04) but decreased /V B (d = 47.3; 95% CI, 26.5 to 68.1; P = 0.028), leading to increased shunt fraction (d = 0.044; 95% CI, 0.039 to 0.049; P < 0.001). SIII was significantly related with (r = 0.49; 95% CI, 0.12 to 0.739; P < 0.001) but not with V B . The strongest association was observed between SIII and mean /V B (r = -0.65; P < 0.0001). Multiple regression demonstrated that had a larger effect on SIII than V B .

Conclusions: SIII is determined not only by heterogeneity but also by and its heterogeneity. The lack of improvement or paradoxical worsening in gas exchange despite mechanical improvement after salbutamol in acute bronchoconstriction is due to increased perfusion of low regions and shunt fraction. These findings provide new insight into monitoring mechanical ventilation and acute bronchoconstriction with capnography.