Lung injury produced by moderate lung overinflation in rats

Abstract

In models using both intact animals and isolated lungs of rats, rabbits, lambs, and dogs, application of high airway pressure and resultant lung overdistension has been shown to cause lung injury. Under pathological conditions, the more normal portions of the lung may be subjected to relative overdistension when supranormal airway pressures are used. A small animal model of lung overdistension is presented here to demonstrate that lung injury can be caused by moderate lung overdistension. Rats were anesthetized with Ketamine and pentobarbital. A tracheostomy was performed and arterial and central venous catheters placed. The animal was placed in a plethysmograph and an infant ventilator was used to provide mechanical ventilation. In the first experiment, animals in group A (n = 6, control) were ventilated at tidal volume (TV) of 5 mL/kg for 5 hours. Animals in group B (n = 6) were ventilated at TV 15 mL/kg for 60 minutes and then were returned TV of 5 mL/kg for the remainder of the experiment. Animals in group C (n = 5) were ventilated at TV 20 mL/kg for 60 minutes and then returned to TV 5 mL/kg. Static lung compliance and arterial blood gasses were measured. Wet and dry lung weight were obtained after sacrifice. In the second experiment, animals in group D (n = 4, control) were ventilated at TV 5 mL/kg for 240 minutes and killed. Animals in group E (n = 4) were ventilated at TV 20 mL/kg for 60 minutes, returned to TV 5 mL/kg, and killed at 240 minutes. Fluorescein-labeled albumin was administered to each animal prior to mechanical ventilation. At sacrifice bronchoalveolar lavage was performed on the right lung. The left lung was fixed for microscopy. Hematocrit, venous oxygenation, and temperature remained stable throughout the experimental period. Group C animals had an elevated PO2 during high volume mechanical ventilation. By the conclusion of the experiment, animals in group B and C were acidotic. Lung compliance fell in all groups. Wet/dry lung weight and dry lung weight/body weight ratios increased in the TV 20 mL/kg group. Analysis of bronchoalveolar lavage fluid for fluoresceine in order to detect capillary-alveolar leak revealed no difference between TV 5 mL/kg (control) and TV 20 mL/kg animals. There was slight perivascular edema in the TV 20 mL/kg specimens. We have demonstrated in a whole animal preparation in rats that lung injury can result from mechanical overdistension with as little as 20 mL/kg for 1 hour.