Early markers of ventilator-induced lung injury in rats

Positive pressure ventilation with hyperdistention of the lungs (PPVHDL) causes microscopic lung injury and elevated lactate dehydrogenase (LDH) levels in rat lung lavage fluid (Behnia et al FASEB J 9-4156,1995). The present study determined other potential indicators of ventilator-induced lung injury in control and PPVHDL rats anesthetized with pentobarbital. While Control rate (n=13) were breathing spontaneously, PPVHDL rate (n-14) were ventilated with 30 % oxygen, with a tidal volume of 18.6 ±4.5 ml/kg, and a respiratory rate of 55-60 per minute. End-tidal CO2 was maintained by increasing deadspace. After 7 hours, rats were killed and the lungs were lavaged with 0.9% NaCI. Red blood cells were present in the sediment of lavage fluid in PPVHDL rats and their lung showed severe congestion, alveolar septa filled with RBCs, and extravasation of red blood cells and inflammatory cells into the alveolar space. Lung lavage fluid LDH and Aspartate aminotransferase (AST) were significantly higher in the PPVHDL compared with the control group (P0.02 and P=0.03, respectively). Electrophoresis of the lavage fluid LDH isoenzymes showed increased peak-5 in the PPVHDL group. Serum LDH, creatinin phosphokinase (CPK), AST, and Kwere significantly higher in the PPVHDL rats, whereas their serum total protein level was significantly lower than the controls (P-0.001). Electrophoretic patterns of serum and lung lavage protein were similar in both groups, suggesting a transmural passage of serum protein from the intravascular to the infra-alveolar space. We found no significant difference between lung tissue endothelin-1 mRNA expression, and lung protein concentration. Lung angiotensin converting enzyme activity, in contrast was significantly lower in PPVHDL rats. LDH, AST and CPK are inexpensive and non-invasive markers for tile assesment of early ventilator-induced lung damage.