We tested the hypothesis that in advanced pulmonary fibrosis, edema is redistributed away from the relatively noncompliant interstitium and predominantly floods alveoli. Severe left lung fibrosis was produced in six dogs with radiation and intratracheal bleomycin and, 24 mo later, hydrostatic edema was induced by infusing 20% body weight Ringer's lactate. Previously we had found, by computed tomography scanning and gravimetry, that similar amounts of water per unit volume accumulated in control and fibrotic lungs; semiquantitative light microscopic grading showed less interstitial and more alveolar edema in the fibrotic lungs. In the present study, we extended these observations with detailed morphometric assessment of volume fractions and absolute volumes of the pulmonary compartments, and we examined the lungs with electron microscopy. We found a twofold rise in the volume fractions of connective tissue and alveolar edema (p < 0.05) and a 50% reduction of air and of interstitial edema in fibrotic lobes (p < 0.05). There was a marked reduction in the absolute volume of edema, paralleling the reduction in lung volume in fibrosis, and minimal gravity-dependent edema gradients in both control and fibrotic lungs. In the latter, evidenced by electron microscopy, the interstitial edema was randomly distributed, whereas in the control lungs, it was found primarily around extra-alveolar vessels and airways, not in the alveolo-capillary septa. We conclude that fibrosis profoundly affects the distribution of edema in the lung.

The pulmonary interstitium acts as an important safety factor against alveolar flooding. To test the hypothesis that in advanced fibrosis, edema is redistributed away from a less compliant interstitium to flood alveoli, we induced severe left lung fibrosis in six dogs with radiation and intratracheal bleomycin. Twenty-four months later, edema was induced by infusing 20% body weight lactated Ringer's solution over 30 min, preceded and followed by computed tomography (CT) scanning. Lower lobes were frozen, and samples were taken for extravascular lung water measurements (Qwl/dQl), regional blood volume, and light microscopic grading of interstitial and alveolar edema. The total volumes of the control and fibrotic lungs were 800 +/- 63 and 45 +/- 10 ml (SE), respectively, indicative of severe fibrosis. Before edema, the fibrotic carinal and basal slices had CT densities 3.5 and 2.2 times greater than respective control slices. After edema, the densities of all control lung slices rose 2.5 times and that of fibrotic carinal and basal slices rose 1.5 times. Edema significantly accentuated the small gravity-dependent gradient in CT density of control lungs, but it had minimal effect on this gradient in fibrotic lungs. The Qwl/dQl for control and fibrotic lower lobes were 8.7 +/- 0.8 and 6.8 +/- 0.7 g H2O/g dry lung, respectively, but the amounts of water per lung volume were similar, and there was no gravity-dependent gradient in Qwl/dQl or in regional blood contents. By light microscopy, we found significantly less interstitial and more alveolar edema in the fibrotic lobes. We conclude that in severe pulmonary fibrosis, similar amounts of water accumulate per lung volume as in controls, and that there is predominant alveolar flooding over interstitial edema. We also conclude that the gravity-dependent gradients in CT densities postedema in the control lungs are not accounted for by edema fluid or congestion, but probably by atelectasis.

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