METHODS

Preliminary investigation suggested that pulmonary periarterial cuffing could be induced most easily in young medium-sized(150225 g) Long-Evans rats made to swim in water at 36 C while breathing 8-10% oxygen. The gas mixture was prepared continuously from N2 and air with flowmeters, and its composition checked frequently by a thermostated oxygen electrode. The flow of gas above the water or through the closed environment was 5 liters/min. The animals were sacrified by either electrocution, decapitation, or pentobarbital(iv) immediately after they were removed from the water or hypoxic environment, or both. The trachea was clamped before the chest was opened to remove the lungs. The left main bronchus was ligated and the inflated left lung was fixed in formalin, sectioned, stained with hematoxylin and eosin, and examined histologically for edema. The right lung was cut and examined for aspiration of bath water (heavily stained with methylene blue), or grossly evident hemorrhage, or edema. Arterial leakage was demonstrated in isolated perfused rat lungs as follows: Under pentobarbital anesthesia (35 mg/kg), a quantity of 12-to 35-diameterpolystyrene microspheres sufficient to completelv obstruct the pulmonary circulation was injected in; o the vena cava. All available blood was then withdrawn from the vena cava into a heparinized syringe. The chest was opened, the left atrium incised, and a catheter tied into the pulmonary artery. The catheter was connected for 10 min to the heparinized blood in a reservoir pressurized to 100 mm Hg. Flow was essentially zero because of the embolization. The lungs were then examined as above.