Maintaining end-expiratory transpulmonary pressure prevents worsening of ventilator-induced lung injury caused by chest wall constriction in surfactant-depleted rats

Abstract

Objective: To see whether in acute lung injury 1) compression of the lungs caused by thoracoabdominal constriction degrades lung function and worsens ventilator-induced lung injury; and 2) maintaining end-expiratory transpulmonary pressure by increasing positive end-expiratory pressure reduces the deleterious effects of chest wall constriction.

Design: Experimental study in rats.

Setting: Physiology laboratory.

Interventions: Acute lung injury was induced in three groups of nine rats by saline lavage. Nine animals immediately killed served as a control group. Group L had lavage only, group LC had the chest wall constricted with an elastic binder, and group LCP had the same chest constriction but with positive end-expiratory pressure raised to maintain end-expiratory transpulmonary pressure. After lavage, all groups were ventilated with the same pattern for 1½ hrs.

Measurements and main results: Transpulmonary pressure, measured with an esophageal balloon catheter, lung volume changes, arterial blood gasses, and pH were assessed during mechanical ventilation. Lung wet-to-dry ratio, albumin, tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and macrophage inflammatory protein-2 in serum and bronchoalveolar lavage fluid and serum E-selectin and von Willebrand Factor were measured at the end of mechanical ventilation. Lavage caused hypoxemia and acidemia, increased lung resistance and elastance, and decreased end-expiratory lung volume. With prolonged mechanical ventilation, lung mechanics, hypoxemia, and wet-to-dry ratio were significantly worse in group LC. Proinflammatory cytokines except E-selectin were elevated in serum and bronchoalveolar lavage fluid in all groups with significantly greater levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in group LC, which also exhibited significantly worse bronchiolar injury and greater heterogeneity of airspace expansion at a fixed transpulmonary pressure than other groups.

Conclusions: Chest wall constriction in acute lung injury reduces lung volume, worsens hypoxemia, and increases pulmonary edema, mechanical abnormalities, proinflammatory mediator release, and histologic signs of ventilator-induced lung injury. Maintaining end-expiratory transpulmonary pressure at preconstriction levels by adding positive end-expiratory pressure prevents these deleterious effects.

Figures

1

Arterial blood pressure (Pa), pH, Pco2, and Po2, under various conditions in groups L, LC, and LCP. * Significant difference from preceding condition. + Significant difference from other groups under the same condition.

2

Interrupter resistance (Rint), dynamic elastance (Edyn) of the chest wall (W) and lung (L), and difference between end-expiratory lung volume and residual volume (EELV-RV), under various conditions in groups L, LC, and LCP. * Significant difference from preceding condition. + Significant difference from other groups under the same condition.

3

Quasi-static inflation P-V curves of the respiratory system (PRS), chest wall (Pw) and lung (PL) before lavage (control), immediately after lavage (and before chest constriction in groups LC and LCP), and at the end of the experiment. Volumes are ml above RV. Bars are SE.

4

Box plots of cytokine concentrations (whiskers indicate 90th and 10th percentiles) in serum and broncho-alveolar lavage fluid (BALF) at the end of the experiment in all groups. Cytokine levels in both serum and BALF were greater than normal values, except IL-1β in serum. + Significantly greater in group LC than in group LCP.