Changes in the mechanical properties of the respiratory system during the development of interstitial lung edema

Abstract

Background: Pulmonary edema induces changes in airway and lung tissues mechanical properties that can be measured by low-frequency forced oscillation technique (FOT). It is preceded by interstitial edema which is characterized by the accumulation of extravascular fluid in the interstitial space of the air-blood barrier. Our aim was to investigate the impact of the early stages of the development of interstitial edema on the mechanical properties of the respiratory system.

Methods: We studied 17 paralysed and mechanically ventilated closed-chest rats (325-375 g). Total input respiratory system impedance (Zrs) was derived from tracheal flow and pressure signals by applying forced oscillations with frequency components from 0.16 to 18.44 Hz distributed in two forcing signals. In 8 animals interstitial lung edema was induced by intravenous infusion of saline solution (0.75 ml/kg/min) for 4 hours; 9 control animals were studied with the same protocol but without infusion. Zrs was measured at the beginning and every 15 min until the end of the experiment.

Results: In the treated group the lung wet-to-dry weight ratio increased from 4.3 +/- 0.72 to 5.23 +/- 0.59, with no histological signs of alveolar flooding. Resistance (Rrs) increased in both groups over time, but to a greater extent in the treated group. Reactance (Xrs) did not change in the control group, while it decreased significantly at all frequencies but one in the treated. Significant changes in Rrs and Xrs were observed starting after ~135 min from the beginning of the infusion. By applying a constant phase model to partition airways and tissue mechanical properties, we observed a mild increase in airways resistance in both groups. A greater and significant increase in tissue damping (from 603.5 +/- 100.3 to 714.5 +/- 81.9 cmH2O/L) and elastance (from 4160.2 +/- 462.6 to 5018.2 +/- 622.5 cmH2O/L) was found only in the treated group.

Conclusion: These results suggest that interstitial edema has a small but significant impact on the mechanical features of lung tissues and that these changes begin at very early stages, before the beginning of accumulation of extravascular fluid into the alveoli.

Figure 1

Experimental set-up.

Figure 2

Effect of interstitial edema on total respiratory system input impedance. Average ± SD resistance (Rrs) and reactance (Xrs) vs. frequency in the control (left) and treated (right) groups at baseline (open circles) and after 240 min at end-experiment (closed circles). The insets are the enlargement of the graphs in the rage of frequencies between 0.5 and 5 Hz. *: significance of the differences between baseline and end-experiment (* for p < 0.05, ** for p < 0.01); +: significance of the differences between the control and treated group.

Figure 3

Changes in Raw and in the constant phase model parameters with time. Time course of Raw and in the parameters of the constant phase model for the control (closed circles) and treated (open circles) animals (mean ± SD). *: significance of the differences with respect to baseline; +: significance of the differences between the control and treated group.