Positive pressure ventilation with hyperdistention of the lungs (PPVHDL) causes microscopic
lung injury in rats and in mice. This study compared lung lavage and serum levels of
lactate dehydrogenase (LDH),
aspartate aminotransferase (AST),
creatinine phosphokinase (CPK), lung lavage and plasma
endothelin-1 (ET-1) concentration, lung tissue ET-1
mRNA expression,
angiotensin converting enzyme (ACE) activity of lung homogenates, and histology of the lung structure in control and PPVHDL rats. Rats were anesthetized with
pentobarbital. While control rats were breathing spontaneously, the PPVHDL rats were ventilated with a rodent
ventilator delivering 30 percent
oxygen, a tidal volume of 18.6 +/- 4.5 ml/kg, and a respiratory rate of 55 to 60 per minute. End-tidal CO2 was maintained at 38-40 mm Hg. After seven hours, rats were killed and the lungs were lavaged. Red blood cells were present in the sediment of lavage fluid in PPVHDL rats and their lung structure showed severe congestion, alveolar septa filled with red cells, and extravasation of red blood cells and inflammatory cells into the alveolar space. Lung lavage fluid AST and LDH were significantly higher in the PPVHDL compared with the control group (P < 0.03 and P < 0.001, respectively). Electrophoresis of the lung lavage LDH showed increased peak-5 in the PPVHDL group. Serum LDH, CPK, AST, and
potassium concentrations [K]+ were significantly higher in the PPVHDL rats whereas their serum total
protein level was significantly lower than the control group (P < 0.001). Electrophoretic patterns of serum and lung lavage
protein were similar in both groups indicating a transmural passage of
serum protein from the intravascular to the intra-alveolar space. No significant difference was found in lung tissue ET-1
mRNA expression and lung
protein concentration between the two groups. Lung ACE activity, in contrast, was significantly lower in PPVHDL rats. This study demonstrated that moderate alveolar hyperdistention caused significant structural lung damage accompanied by decreased ACE activity after seven hours of
mechanical ventilation and that elevated lung lavage and serum LDH and AST levels in lung lavage and in serum might be early markers of
ventilator-induced lung injury in this rat model.