Effects of pulmonary fibrosis on the distribution of edema. Computed tomographic scanning and morphology.

Abstract

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.

Evaluation of Pulmonary Edema: Stereological versus Gravimetrical Analysis

“…Although cryofixation is considered to be the best means to avoid tissue shrinkage due to loss of fluid [22], it does not allow for stereological sampling. Previous studies clearly demonstrated that pulmonary edema can be validly quantified in chemically fixed tissue samples by light microscopy [7,[23][24][25]. After dehydration alveolar edema is preserved as proteinaceous intraalveolar precipitates which indicate the former fluid level in the alveolar lumen.…”

The Rationale for Fluid Restriction During Treatment for ARDS

“…The capacity of the perivascular interstitium depends on (1) the degree of lung infla tion, which can increase the capacity 20-fold; (2) the presence or absence of ventilation; (3) the time for accumulation of fluid; (4) the integrity of the alveolar epithelium; and (5) the interstitial compli ance and pressure gradients which favor filtration and clearance toward the hilum. 14 Although interstitial edema is presumably a necessary antecedent to the development of alveo lar edema, it is not at all clear that once alveolar edema has developed, further accumulation of that edema is accurately described by the Starling equa tion. The onset of alveolar edema, in contrast, is a function of a different set of less well understood factors that result in the all-or-none development of alveolar edema.…”

Respiratory mechanics and gas exchange in postobstructive pulmonary vasculopathy

“…Ligation of the left main pulmonary artery was carried out as described previously [4,14]. Briefly, the animals were anaesthetized with pentobarbital sodium (25 mg·kg -1 ), intubated and ventilated with 100% O 2 .…”