Pulmonary microvascular and alveolar epithelial permeability characteristics in N-nitroso-N-methylurethane-injected...

The subcutaneous injection of 5 to 6 mg/kg of body weight of N-nitroso-N-methylurethane (NNNMU) has been reported to cause acute alveolar injury in animals. To determine the permeability characteristics of the alveolar epithelium, we employed the in vivo saline-filled dog lung model and determined the time to 50 percent equilibration in minutes of a specific tracer in the blood and the lung model and determined the time to 50 percent equilibration in minutes of a specific tracer in the blood and the lung liquid (T 1/2) for endogenous serum albumin (MW 69,000 daltons, molecular radius 35 A) and exogenously administered 500,000 MW polydispersed dextrans (molecular radius 200 A). Compared to control animals, T1/2 decreased (permeability increased) in NNNMU-injected dogs from 3,500 +/- 100 to 682 +/- 160 minutes for albumin and from 20,000 +/- 250 to 2,790 +/- 750 minutes for 500,000 MW dextran (P less than 0.001). To determine the permeability characteristics of the pulmonary microvasculature, we employed the right lymph duct cannulation dog model and measured lymph flow/30 minutes, lymph albumin and dextran concentration, and lymph/plasma albumin and dextran ratios in control and NNNMU-injected dogs. Compared to control animals, lymph flow was significantly greater in NNNMU dogs, 2.07 +/- 1.1 vs .71 +/- .50 ml/30 minutes (P less than 0.01), respectively. We conclude that NNNMU injection increases permeability in both the alveolar epithelium and the pulmonary microvasculature.