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

Wellman TJ, Winkler T, Costa ELV, Musch G, Harris RS, Venegas JG, Vidal Melo MF. Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs. J Appl Physiol 113: 947-957, 2012. First published June 7, 2012; doi:10.1152/japplphysiol.01631.2011.-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 (NN)-N-13 with positron emission tomography to examine how specific ventilation (s(V) over dot) 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 cmH(2)O) (n = 4). We quantified fractional gas content with transmission scans, and s(V) over dot with emission scans of infused (NN)-N-13-saline. Voxel (NN)-N-13-washout curves were fit with one-or two-compartment models to estimate s(V) over dot. Total heterogeneity, measured as SD[ log(10)(s(V) over dot)], was divided into length-scale ranges by measuring changes in variance of log(10)(s(V) over dot), resulting from progressive filtering of s(V) over dot images. High-VT ZEEP showed higher s(V) over dot 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 s(V) over dot 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 s(V) over dot 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 s(V) over dot 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 s(V) over dot heterogeneity by maintaining lung expansion and airway patency at those small length scales.