Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs

Abstract

Heterogeneous, small-airway diameters and alveolar derecruitment in poorly aerated regions of normal lungs could produce ventilation heterogeneity at those anatomic levels. We modeled the washout kinetics of 13NN with positron emission tomography to examine how specific ventilation (sV̇) heterogeneity at different length scales is influenced by lung aeration. Three groups of anesthetized, supine sheep were studied: high tidal volume (Vt; 18.4 ± 4.2 ml/kg) and zero end-expiratory pressure (ZEEP) ( n = 6); low Vt (9.2 ± 1.0 ml/kg) and ZEEP ( n = 6); and low Vt (8.2 ± 0.2 ml/kg) and positive end-expiratory pressure (PEEP; 19 ± 1 cmH2O) ( n = 4). We quantified fractional gas content with transmission scans, and sV̇ with emission scans of infused 13NN-saline. Voxel 13NN-washout curves were fit with one- or two-compartment models to estimate sV̇. Total heterogeneity, measured as SD[log10(sV̇)], was divided into length-scale ranges by measuring changes in variance of log10(sV̇), resulting from progressive filtering of sV̇ images. High-Vt ZEEP showed higher sV̇ heterogeneity at <12- ( P < 0.01), 12- to 36- ( P < 0.01), and 36- to 60-mm ( P < 0.05) length scales compared with low-Vt PEEP, with low-Vt ZEEP in between. Increased heterogeneity was associated with the emergence of low sV̇ units in poorly aerated regions, with a high correlation ( r = 0.95, P < 0.001) between total heterogeneity and the fraction of lung with slow washout. Regional mean fractional gas content was inversely correlated with regional sV̇ heterogeneity at <12- ( r = −0.67), 12- to 36- ( r = −0.74), and >36-mm ( r = −0.72) length scales ( P < 0.001). We conclude that sV̇ heterogeneity at length scales <60 mm increases in poorly aerated regions of mechanically ventilated normal lungs, likely due to heterogeneous small-airway narrowing and alveolar derecruitment. PEEP reduces sV̇ heterogeneity by maintaining lung expansion and airway patency at those small length scales.